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Brain Tumours New Horizons, New Thoughts – The Hans India

A century has elapsed since the first successful brain tumour surgery was performed by the "" FATHER OF NEUROSURGERY "" DR HARVEY CUSHING.

In the following 70 years progress was made in all basic aspects of diagnosis and management of brain tumours.

The introduction of CT SCAN in 1971 the brain tumours diagnosis became fast,accurate,specific and easier. The lengthy , laborious,risky and invasive investigative procedures became the things of past.

In INDIA about 40-50,000 people are diagnosed with brain tumours and successfully managed with very good results.

Even then the fear of brain tumour diagnosis and pessimism regarding the surgery outcome are prevalent even today.

The popular impression in general public is that brain tumours are VERY COMMON & all are UNIFORMLY CANCEROUS is without scientific basis.

In fact brain cancers incidence is 2-3% per one lakh population,amounting to LESS than 2% of all cancers in human body.

It is very important to note that only ONE THIRD (1/3)of are all brain tumours are cancerous while there about 125 varieties of such .

Equally important to state that chances of any person to develop a MALIGNANT TUMOUR in their life span is LESS Than 1% .

Presenting symptoms are::

Morning headaches mainly in forehead

Vomitings

Double vision

Epilepsy

Memory disturbances

Loss of vision , smell , hearing particularly ONE SIDE

weakness of one half of body

Swallowing difficulty

Walking disturbance

Unclear speech

Menstrual cycle irregularity

Drowsy or unconscious

INVESTIGATIONS ::

Ct scan brain: PLAIN & CONTRAST MRI BRAIN WITH CONTRAT PET SCAN BRAIN rarely

Causative factors of brain tumours::

For a long time it was said to be UNKNOWN

Now with improved research and surveillance few causes are mentioned like:

1 Stress

2. Exposure to radiation

3. Exposure to chemicals like PESTICIDES, OIL PRODUCTS, RUBBER , CHLORINATED INDUSTRIAL SOLVENTS

4. Genetic factors and family history

5. Life style choices like Wrong diet disrupted sleep Sedentary life style Alcohol SmokingObesity

6. Vitamin deficiency like Vitamin c, beta carotene , folate

Brain tumours can develop in all AGE GROUPS mainly CHILDREN & ADULTS

Brain tumours are mainly two Varieties

PRIMARY & SECONDARY

PRIMARY: Tumours developing in brain , brain coverings & cranial nerves.

SECONDARY: Also known as METASTATIC TUMOURS from other parts of body like THYROID ,LUNG, BREAST , KIDNEY & INTESTINES secondary tumours amount to 40% of total brain tumours.

Once brain tumours are confirmed the line of treatment is SURGERY.

Nowadays tumours of less than 2 CENTIMETRES size are managed with radiotherapy if there is no significant brain compression.

Advances in surgical techniques and surgical equipment like NEURONAVIGATION, ULTRASOUND SURGICAL ASPIRATOR , OPERATING MICROSCOPE, intraoperative MRI and CT Scan, cortical mapping and AWAKE PRECEDURES have made possible access to & total removal of tumours with presentation of vital brain functions.

Of the primary brain tumours there are TWO IMPORTANT DIVISIONS.

1. CANCEROUS or MALIGNANT

2. NONMALIGNANT of BENIGN

BENIGN tumour are mostly removed completely with total CURE to patients. Some residual tumours in a critical brain area are managed with latest radiation methods.

Cancerous tumours are excised to the maximum possible without compromising important brain functions followed by adjuvant latest modalities of treatment.

The most malignant primary brain tumour called as GLIOBLASTOMA MULTI FORME was associated with poor outcome and testing the nerves of affected patients as well as treating neurosurgeons.

In fact almost half of these patients are alive at 2 YEARS an impressive result considering previous survival was thought to be LESS THAN A YEAR!!!!

It is no exaggeration to state that few lucky patients with GLIOBLASTOMA are living for 5,10,20 years

This is possible with advances in several areas like :

MOLECULAR ONCOGENESIS with identification of deletions in chromosome segments 1P &2Q

ADVANCES in imaging like functional localisations,spectroscopy ,diffusion and perfusion measurements ,diffusion tensor imaging to visualise white fibre tracts

Effectiveness of CHEMOTHERAPY and delivery of drugs placing catheters and TARGETED THERAPY

Most recently STEM CELLS have been used to target brain tumours

MULTI DISCIPLINARY approach in addressing the diversity and complexity of brain tumours is the key for successful results

In the few important points to remember:

1. NOT ALL BRAIN TUMOURS ARE CANCEROUS

2. Whole skull is NOT OPENED during surgery

2.brain tumour surgery is reasonably SAFE

3. Most of the times patient is CONSCIOUS after surgery

4. Within 12 hours patients are given feeds

5. Mobilisation at the earliest

6. Early diagnosis and treatment is mandatory for good results

7.Present day RADIOTHERAPY techniques are SAFE DELIVERS HIGHER DOSES IN PRECISE LOCATION & LEAST DAMAGE TO THE SURROUNDING NORMAL BRAIN STRUCTURES

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Brain Tumours New Horizons, New Thoughts - The Hans India

Top 5 Lab-Grown Meat Stocks to Invest In ([month] [year]) – Securities.io

Can Meat Become Animal-free?

Since the dawn of civilization, food has come from two sources only: plants and animals. The hunter-gatherers got plants from foraging and hunting. The later farming culture would plant crops and raise livestock.

Meat consumption has been part of most food cultures ever since. So while veganism is definitely a growing trend, there are a lot of consumers that are very reluctant to give up meat. There are also a lot of vegans avoiding meat consumption over ethical grounds (animal rights) but who would love a suffering-free meat option.

And there is also the environmental concern. Cattle farming is a massive methane producer (a powerful greenhouse gas) and also a massive consumer of land and water.

This is why a new category of innovative startups is working on an alternative, with $2B invested in the sector in 2022. What you could grow in a lab is the final product, animal muscle tissues, without having to ever kill an animal.

Growing a steak directly in a lab is far from an easy task. Muscles are complex tissues that are hard to replicate artificially. And most of the culinary qualities come from an elaborate mix of different tissues, highly specialized cells, and a complex chemical mix.

The first problem is acquiring good stem cell lines. It can be a technical and expensive process.

The next issue is having the muscle cells grow in the form of a solid and tasty steak, instead of a half-liquid mush of cells. The solution is to use scaffolding, using material like cellulose or artificial material to provide the shape of the future meat. The difficulty of missing blood vessels in the meat is an extra complication.

And lastly, there is the question of cost. The lab-grown meat industry uses a lot of high-tech solutions and highly-trained scientists. But it has to compete with just feeding a cow and then killing it.So scaling-up and cost-efficient methods are a must for the product to go beyond a small niche.

This list has been made from a subjective analysis of assessing technology and the financial position of the companies. They are ordered from largest to smallest market capitalization. This is for educational purposes and not investment advice.

Tyson is a giant in food production, especially meat products, providing 20% of the meat consumed in the US. So this is an investment that might be putting off investors seeing it as an ethical issue.

It is nevertheless a large investor in alternatives to meat through its venture capital branch, Tyson Venture.

It includes a 5% stake in plant-based meat substitute Beyond Meat and investments in Future Meat Technologies and Upside Foods. Upside food became a $1B company in 2022 and Future Meat reach a cost of $7.7/pound of chicken in 2021.

Tyson also invested in mushroom fermentation technology, genomic food safety, a food ordering app, and plant-based shrimp products.

Tyson Food is a $21B company, with 2022s revenues of $53B and $3.4B in net income. This makes it a very safe bet for investors looking for exposure to meat-substitute, both plant-based and lab-grown.

If society starts to turn away from conventional meat products, Tyson will be able to rely on its investment to keep its business stable. And if it does not happen, it will continue to benefit from its dominant position in the traditional meat market.

Another meat giant, but from Brazil, with 250,000 employees. While it is primarily focused on meat, it is also involved in afferent business like cold chain, leather products, collagen and logistics, for a total of 42 brands.

The company has invested $100M in 2021 for acquiring Spanish startup BioTech Foods and building an R&D center in Brazil. Commercial production is expected to start in 2024.

In 2021, it also acquired Dutch company Vivera, Europes largest independent plant-based food company, for $341M, adding to a previous similar acquisition of Seara. All significant investments for the $7.8B company.

As for Tyson, this is a bet on dominant meat processors staying the leader of the industry, either with traditional products or with new alternatives. It also provides exposure to South American and European markets.

Agronomics is a venture fund focused on lab-cultivated cells.

This includes lab-grown meat, but also alternatives to leather, eggs, dairy, as well as plant-based alternative, lab-cultivated chocolate, lab-cultivated cotton, and lab-cultivated pet food.

The portfolio is quite diverse, with various geography, segment and startup maturity and the largest investment in one companyjust 11.4% of the total portfolio, and most below 5%.

Source: Agronomics

The company was a pioneer in the field, starting in 2018.So far, gross IRR (Internal Rates or Returns) have been an excellent 23%, with Agronomics Limited leading 14 funding rounds.

This company offers an interesting option for diversified exposure to the sector, while letting VC specialists handle the research and pick what they consider the most interesting deals.

Another venture focused on innovative food products. The company was founded by Brendan Braziers, one of the co-developer of the Beyond Meat burger.

It is currently invested in 18 companies, including Eat Just, the first company in the world to have commercialized lab-grown meat (approved in 2020 in Singapore). The rest of the portfolio includes lab-grown meat, eggs, coffee, seafood, dairy, honey, gelatin, and chocolate.

Like for Agronomics Limited, as it only invests in pre-revenue startups, it is too early to use earnings or cash flow as a metric. It is a bet that lab-grown meat will reach the point where it is widely consumed and is profitable thanks to a decrease in costs and technological improvements.

Together, these 2 venture investments can offer very diversified exposure to lab-grown food products.

Also formerly known as MeaTech 3D Ltd. The company has 80 employees, with a presence in Israel, Belgium, and the USA, and raised a total of $54M. It is also one of the rare lab-grown meat companies that have not been acquired by a larger company and chose to be publicly listed.

Steakholder relies on tissue 3D printing for the production of its meat and submitted 18 patents on that topic (4 patents granted so far). It should allow it to fully replicate the look and texture of full-animal meat, aka structured meat.

The company is aiming to submit its products to regulators in early 2023 in Singapore and in late 2023 for the USA and EU. So the company is, for now, pre-revenue but could reach commercialization soon.

With barely a double-digit market cap, Steakholder is a bet that their 3D printing technology can allow for a superior product, quick growth and more fundraising.

The company had $11M in cash in Q3 2022, for a quarterly loss of $2.5M. The stock listing might be forced to move from NASDAQ to the OTC market as it has recently been trading below $1/share.

Investors interested in that sector can choose between a few different strategies.

The first one is to count on the dominant meat sellers to keep their grip over the market, through their marketing firepower, distribution network, and deep pocket. In this context, lab-grown meat would not really change the market structure, just the products sold.

Another option is to hope for newcomers to be more innovative and efficient, and able to create a whole new segment that they will come to dominate. In that case, if the bet is on the sector in general, investment in diversified venture firms allows to not have to pick a winner and just let VC do the leg work of research and due diligence.

Lastly, investing directly in individual companies is an option. For now, the choice is quite limited, but many of the currently private cultured meat companies will try to IPO in the future. This can be riskier, but also more profitable if the stock selection turns out to be the right one.

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Top 5 Lab-Grown Meat Stocks to Invest In ([month] [year]) - Securities.io

Roundtable Discussion: Krishnan Debates the Rationale For … – Targeted Oncology

Amrita Krishnan, MD (Moderator)

Director of the Judy and Bernard Briskin Center for Multiple Myeloma Research

City of Hope

Duarte, CA

CASE SUMMARY

A 60-year-old White woman was diagnosed with stage II multiple myeloma. She has a history of being a heavy smoker, with a gain (1q21) of cytogenetics and an ECOG performance score of 0. At the time, she was treated with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd) induction therapy, followed by autologous stem cell transplantation. She achieved a complete remission with VRd and transplant and was minimal residual disease negative, then placed on lenalidomide maintenance therapy.

At a follow-up after 2 years on lenalidomide maintenance, the patient reported having severe fatigue and pain in her back and legs, which was disrupting her ability to continue working full time. A PET scan shows vertebral fracture at L1, lesions in both femurs, and an ECOG performance score of 1. Her current lab levels are now the following:

KRISHNAN: We have [a case here] with a biochemical and clinical progression.

Some of the [factors] to talk about are [whether] they are early vs late relapse, and [whether] that influences your decisions in terms of therapy?

CHHABRA: I tend to think patients who receive lenalidomide [Revlimid] maintenance, if they progress less than 36 months, [are considered an] early relapse patient. If they did not receive maintenance, then 18 months [is when I would consider them an early relapse patient]. Thats been my rule of thumb.

Although Ive also heard that 24 months is a good cutoff between early and late relapse. My preferred second-line regimen is not influenced by early vs late relapse, because Ive been using daratumumab [Darzalex]-based therapy, typically in combination with carfilzomib [Kyprolis] and dexamethasone [DKd]. If I have a clinical trial that is specifically for patients in the high-risk category, early relapse [is considered] less than 18 monthssuch as the allogeneic transplant trial, [with patients who] had less than 18 months from transplant.

KRISHNAN: Lets see [whether] every-one else agrees with you in terms of [the following]: (1) early relapse and (2) it sounds like youre a big DKd fan. Dr Lashkari, are you on the DKd bandwagon for first relapse?

LASHKARI: I would certainly recognize this as being a more aggressive relapse in a patient. I think youre right, [that] if this patient were treated initially, we would consider giving a daratumumab-based induction therapy, but she did very well, which is interesting. She had a complete response, and one can argue that if someone became [minimal residual disease] negative, it almost doesnt matter how you get there if you get there, because that in and of itself tends to portend a good prognosis. Considering someone relapsing within a couple years; invariably, this patient relapsed within 2 years because we see an M spike of 1.98 g.

Biochemical progression would have been defined as having greater than 0.5 g/dL, and that may have developed within a year from time of transplant. I would consider this patient to be an early relapse with aggressive clinical features, but I would certainly rebiopsy them to see what other clones are present.

In terms of treatment options, its interesting to get the information to come back. I dont know [whether] we can guide based on the information that comes back necessarily, unless perhaps they had an 11;14 translocation, in which case you can consider a venetoclax [Venclexta]-based treatment. I probably wouldnt even consider that for such a patient if they havent received a CD38 antibody. DKd is reasonable, and another option would be to go to daratumumab, pomalidomide [Pomalyst], and dexamethasone [DPd] as another option.

KRISHNAN: [Are there] any other takers for DPd instead? It sounds like everyone would agree with daratumumab, but its really what the partner would be. Would anyone pick DPd?

CHAND: I tend to use more DPd compared [with] DKd, because in my experience, scheduling and monitoring is a little easier on this regimen. It tends to work well in patients who are refractory to lenalidomide. I just find it more tolerable. The cytopenias are a little bit less compared [with] the DKd, too.

AMBIKA: I tend to use more DPd, toofor the same reasons as [others mentioned]and use carfilzomib, cyclophosphamide, and dexamethasone [KCd] as the next-line [treatment], like carfilzomib plus cyclophosphamide. I went through that route in a few patients and they did OK.

DEKKER: I typically use carfilzomib. [Patients] come to [the] infusion center already, so they will get carfilzomib as well. Plus, carfilzomib is a potentially more powerful agent, and I use it once a week. If [patients] develop cardiac toxicities [within the first 2 or 3 weeks], I back off. If they dont, they typically would do well and tolerate it for a long time.

CHAUDHARY: Myelosuppression is less with DPd, in my experience, if you dose reduce the pomalidomide.

KRISHNAN: It sounds like were pretty much split [between] DPd and DKd, both being valid regimens in that early 1- to 3-[year] relapse setting. What Im hearing from people is to pick your adverse events [AEs], as well, and Im guessing [that] if someone had prior cardiac history, more clinicians would [choose to use] DPd. But let me ask a more challenging question. Ive not heard a single person say IPd [isatuximab-irfc (Sarclisa), pomalidomide, dexamethasone] or IKd [isatuximab, carfilzomib, dexamethasone]. Is anyone using isatuximab?

MURAD: Thats our preferred drug, but thats definitely a reasonable option. I dont think theres any problem with carfilzomib.

DEKKER: I use daratumumab and isatuximab. Clearly, subcutaneous administration is a plus, but I had a few patients who had a cutaneous reaction or had skin conditions, so I decided to go with isatuximab.

KRISHNAN: Do most [of you] feel theyre comparable, or do [you] feel that theres a difference?

DEKKER: I think theyre probably comparable. I do think [that] sometimes later products may have some advantages, because they know the issues with the original product and tried to tweak the molecule a little bit. So theoretically, I would say isatuximab may be a bit better, but the problem is daratumumab is good enough on its own, so Im doubtful we will find much of the difference. We could keep analyzing the data and find a subtype, a subgroup here or there, or a special population that will be beneficial. But for both [medications, it is] likely all the data will come down to the same ballpark.

KRISHNAN: Im just curious, Dr Dekker, when you say you think isatuximab is better, is it in terms of [AEs] or efficacy?

DEKKER: Both, because again, they look at the molecule, they see off-target effects, and they see where the escape mechanisms are. So when they manufacture the molecule, all this minor tweaking in the design may help to both improve efficacy and decrease toxicity. But how clinically significant that is, how truly that will translate into something meaningful in clinical practice without head-to-head datathat will be impossible to determine.

KRISHNAN: So if I could summarize, most [of you] are convinced [of using] CD38 antibody without, and finding them interchangeable depending on their practice and some specific patient issues. Then its really the partner to that antibody, right?

MUKHERJEE: Yeah, Im comfortable with using daratumumab now and usually do introduce that in the second line. Depending on the other comorbidities of the patient, if they have cardiac issues, then I would go with pomalidomide. If not, then carfilzomib. Im comfortable with daratumumab, but Im not that comfortable with isatuximab yet.

KRISHNAN: Thats interesting. I will give you a look to the future. Theres a phase 3 trial ongoing, [comparing] DPd[with] teclistamab-cqyv [Tecvayli], pomalidomide, and dexamethasone, so that will be interestingthe T-cell engager, the new drug that just got approved, then being moved into that early relapse setting. I think many of you are familiar with the CARTITUDE-1 trial [NCT03548207], also in the earlier relapse setting.1

What will be interesting [is that in 2024 or 2025], myeloma may look completely different. We [may] see T-cell engaging therapy moved up earlier, in part because the CD38 antibodies are [also] going to be moved up even earlier, in terms of their use in induction therapy. I think that is the challenge in myeloma.

DISCUSSION QUESTION

KRISHNAN: I think the [PFS data for these regimens are] what people responded to, [those] who wanted to use carfilzomib as the partner to CD38. In the IKEMA trial [NCT03275285], which compared IKd vs Kd [carfilzomib and dexamethasone], the PFS is decent and youre getting almost 3.5 years out of a first relapse regimen [From the Data2].

In the CANDOR trial [NCT03158688], [the PFS is approximately] 2.5 years, [comparing DKd vs Kd].3 And then [the PFS] goes down from there in the CASTOR [NCT02136134], ICARIA-MM [NCT02990338], APOLLO [NCT03180736], and OPTIMISMM trials [NCT01734928].4-7 Interestinglyand I use a lot of DPdif you compare the PFS, its not as great at [approximately 1] year based on the APOLLO study, and IPd is the same at [approximately 1] year.5,6

DISCUSSION QUESTION

KRISHNAN: This patient did have some mild renal impairment, [as well as] the genetic risk with the [1q21 gain]. It sounds like that would push you a little bit more, as well.

LASHKARI: The 1 issue I think a lot of us have who see these patients with myeloma is that carfilzomib is a great drug, but its not without some of its own AEs in terms of cytopenias, fluid retention, and sometimes infusion reactions. And for the [patients who] are just in your office all the time, I feel for them. Thats another potential barrier, especially if youre dealing with patients who may not be as robust as others.

That is a big factor that plays into my thinking for maybe not using carfilzomib at this time. Maybe I should be changing my mind if the dataas we saw with the 2 trials evaluating carfilzomib with daratumumab or isatuximabare truly what you get out of it. Maybe that is a better option, but it may be a slightly harder sell for patients, especially those [who] value their quality of life and the amount of time that theyre not spending at your office.

KRISHNAN: I do think its a potent regimen. I tend to use it in younger patients, because I do think, in the CANDOR study, [most] of the deaths were in patients [older than] 65 [years], and more infectious death.3 In older patients, I tend to be a little more cautious about using it, and I only do it in older patients when my back is against the wall and they have really aggressive disease.

Otherwise, I do use it in younger patients with aggressive disease. In other younger patients, I try to, but to your point, a lot of younger patients tend to still be working, and coming into the office even once a week can be challenging. So lifestyle and patient preference also play an important role.

REFERENCES

1. Martin T, Usmani SZ, Berdeja JG, et al. Ciltacabtagene autoleucel, an anti-B-cell maturation antigen chimeric antigen receptor T-cell therapy, for relapsed/refractory multiple myeloma: CARTITUDE-1 2-year follow-up.J Clin Oncol. 2022;JCO2200842. doi:10.1200/JCO.22.00842

2. Moreau P, Dimopoulos MA, Mikhael J, et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial.Lancet. 2021;397(10292):2361-2371. doi:10.1016/S0140-6736(21)00592-4

3. Usmani SZ, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study.Lancet Oncol. 2022;23(1):65-76. doi:10.1016/S1470-2045(21)00579-9

4. Spencer A, Lentzsch S, Weisel K, et al. Daratumumab plus bortezomib and dexamethasoneversusbortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR.Haematologica. 2018;103(12):2079-2087. doi:10.3324/haematol.2018.194118

5. Richardson PG, Perrot A, San-Miguel J, et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study. Lancet Oncol. 2022;23(3):416-427. doi:10.1016/S1470-2045(22)00019-5

6. Dimopoulos MA, Terpos E, Boccadoro M, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial.Lancet Oncol. 2021;22(6):801-812. doi:10.1016/S1470-2045(21)00128-5

7. Richardson PG, Oriol A, Beksac M, et al. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial.Lancet Oncol. 2019;20(6):781-794. doi:10.1016/S1470-2045(19)30152-4

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Roundtable Discussion: Krishnan Debates the Rationale For ... - Targeted Oncology

Second-line Axi-cel Elicits OS Benefit in Relapsed/Refractory LBCL – OncLive

Image Credit: Dr_Microbe - stock.adobe.com

Axicabtagene ciloleucel (axi-cel; Yescarta) produced a statistically significant improvement in overall survival (OS) compared with standard-of-care (SOC) therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL) within 12 months of completion of first-line therapy, according to data from the primary OS analysis of the phase 3 ZUMA-7 trial (NCT03391466).1

Investigators plan to present full results from the OS analysis at an upcoming medical meeting.

Prior data from ZUMA-7 supported the FDA approval of axi-cel for the treatment of adult patients with LBCL that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy in April 2022.2

Findings for the primary end point of event-free survival (EFS) showed that at a median follow-up of 24.9 months, axi-cel generated an estimated median EFS of 8.3 months (95% CI, 4.5-15.8) compared with 2.0 months (95% CI, 1.6-2.8) with SOC treatment (HR, 0.40; 95% CI, 0.31-0.51; P <.0001). The estimated 18-month EFS rates in the experimental and control arms were 41.5% (95% CI, 34.2%-48.6%) and 17.0% (95% CI, 11.8%-23.0%), respectively.

Additionally, axi-cel elicited an objective response rate (ORR) of 83% (95% CI, 77%-88%) vs 50% (95% CI, 43%-58%) for SOC.

The randomized, open-label, global, multicenter, phase 3 ZUMA-7 study enrolled 359 patients with relapsed/refractory LBCL within 12 months of first-line therapy.3 First-line treatment needed to consist of an anti-CD20 monoclonal antibody, unless the investigator determined that tumor was CD20 negative, and an anthracycline-containing chemotherapy regimen.

Patients were excluded from the trial if they had a history of malignancy other than non-melanoma skin cancer or carcinoma in situ unless they were disease free for at least 3 years; received more than 1 line of therapy for LBCL; or had a history of autologous or allogeneic stem cell transplant.

Patients were randomly assigned 1:1 to a single infusion of axi-cel or SOC treatment with platinum-containing salvage chemotherapy followed by high-dose therapy and autologous stem cell transplant in responders.

Along with the primary end point of EFS, OS was designated as a clinically important prespecified key secondary endpoint. Other secondary end points included ORR, patient-reported outcomes, and safety.1

Regarding safety, findings from ZUMA-7 showed that axi-cel displayed a safety profile consistent with previous studies. Among the 168 patients evaluable for safety who received axi-cel, grade 3 or higher cytokine release syndrome (CRS) was reported in 7% of patients, and neurologic events occurred in 25% of patients. In the SOC arm, 83% of patients had high-grade adverse effects, mostly consisting of cytopenias.

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Second-line Axi-cel Elicits OS Benefit in Relapsed/Refractory LBCL - OncLive

MRI-guided Radiation Therapy Systems Revenue to Top US$2.89 … – GlobeNewswire

Rockville, March 27, 2023 (GLOBE NEWSWIRE) -- The market for MRI-guided radiation therapy systems is currently valued at US$ 545.1 million and is anticipated to generate US$ 2.89 billion in sales by the end of 2033. According to Fact.MR study, sales of MRI-guided radiation therapy systems will significantly increase at a 18.1% CAGR over the next 10 years.

Since MRI-guided radiation therapy systems are widely used in the treatment of cancer, the rising incidence of various malignancies is anticipated to significantly boost market growth over the course of the forecast period. It is also projected that rising capital spending on establishing healthcare infrastructure in developing economies would increase shipments of MRI-guided radiation therapy equipment in the future.

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Drivers

Restraints

Trends

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Regional Landscape:United States is expected to account for a substantial share in the market. Various factors such as developed healthcare infrastructure and the significant presence of reimbursement policies in the United States are expected to boost the adoption of MRI-guided radiation therapy systems.

Competitive LandscapeMRI-guided Radiation therapy systems market is highly consolidated. Companies such as Elekta AB and ViewRay are dominating the global market and currently, account for around 80% of the global market share.

In addition to this, companies are receiving FDA approvals to expand their sales potential across various countries.

Key Companies Profiled

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Key Questions Covered in the MRI-guided Radiation Therapy Systems Market Report

Check out more related studies published by Fact.MR Research:Hormone Replacement Therapy Market Size: The global hormone replacement therapy market size is estimated at USD 18.4 Billion in 2022 and is forecast to surpass USD 32.8 Billion by 2032, growing at a CAGR of 5.9% from 2022 to 2032.

Dual Therapy Stent Market Sales: The global duel therapy stent market sales valued at USD 11.09 Billion in 2022. The market is estimated to surpass a valuation of USD 23.07 Billion by 2032. The forecast duration of this report is 2022- 2032.

Rheumatoid Arthritis Stem Cell Therapy Market Share: The global rheumatoid arthritis stem cell therapy market share account for a share of USD 23.42 Billion in 2022. The market is anticipated to surpass the valuation of USD 33.30 Billion by end of the forecast period i.e. 2032. The rheumatoid arthritis stem cell market is expected to grow with a CAGR of 4.5 %.

Dual Antiplatelet Therapy Market Growth: Emergence of more effective oral and other anticoagulants may also hamper the market growth. In addition, high cost associated with the therapy and lack of its awareness in various regions across the globe will possibly confine the dual antiplatelet therapy market growth.

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MRI-guided Radiation Therapy Systems Revenue to Top US$2.89 ... - GlobeNewswire

Rise in Prostate Cancer Cases Contributes to Challenges in Care – Targeted Oncology

Murugesan Manoharan, MD, FRACS

Troubling news about prostate cancer emerged from the American Cancer Society (ACS) in January. In its Cancer Statistics 2023 study1, published in the journal CA: A Cancer Journal for Clinicians, ACS scientists announced:

These findings are due in part to the US Preventive Services Task Forces 2012 recommendation to cease PSA screening in all men. Since then, early diagnosis and treatment of prostate cancer has dropped, while advanced prostate cancer cases have begun a steady rise.

I have observed several factors in play at Miami Cancer Institute as we respond to the challenge of prostate cancer.

Cost of PSA Screening

I concur with the ACS recommendation that men of all ages should have an opportunity to make an informed decision about whether prostate cancer screening is right for them. Balanced and unbiased counsel from the physician is vital. However, the cost of testing may be a barrier for some patients, as many insurance plans do not cover it. I have observed that wealthier patients in urban areas are more likely to have access to timely screening, while lower-income and minority individuals do not. The latter group includes many of my patients in the Haitian American community, who have a significant incidence of aggressive prostate cancer.

Plentiful Treatment Options

The array of prostate cancer treatments includes robotic surgery, external beam radiation including proton beam therapy, brachytherapy, cryotherapy, high-intensity focused ultrasound (HIFU), laser ablation, hormone and other drug therapy, chemotherapy, immunotherapy, and more. Direct-to-consumer marketing touting these various treatments can confuse and overwhelm patients. Again, careful consultation with an unbiased urologic oncologist is critical.

Image Credit Sheitipaves [stock.adobe.com

FDA Reviews

While the US is quite advanced in prostate cancer treatment, The FDAs ultra-cautious approach to approvals results in a lag in new-technology adoption.

For example, prostate specific membrane antigen (PSMA PET Imaging, which can accurately detect the spread of prostate cancer spread using a radioactive tracer, has been in use internationally since around 2014, but the FDA delayed its broad national approval of this technology until 2021.

High Intensity Focused Ultrasound (HIFU) therapy was studied as early as the 1940s and researchers focused on HIFU for the prostate in the 1990s. The treatment was approved in more than 20 countries, including Canada and Australia, before finally receiving FDA approval in 2015.

Last, the NanoKnife system, which employs low-energy, direct-current electrical pulses to destroy cancerous cells,was first made commercially available in 2009 but the FDA approved a pilot study only in 2019.

These technologies were widely used in cancer centers around the US prior to full FDA approval but since they werent covered by insurance, they were out of reach for many patients who could have benefited.

Promoting Good Quality-of-Life

Death isnt the only outcome of a prostate cancer diagnosis. The statistics dont account for the pain, suffering, and inconvenience patients may endure while undergoing treatment. My team and I focus on helping patients maintain a good quality of life while we work towards a cure. Our patients express several priorities as they prepare for prostate cancer treatment:

A quick recovery: patients want to get back to work and everyday living. Technological advances such as minimally invasive surgery (sometimes with a single small incision) help make this possible. Many patients go home 24 hours after surgery. Once their pain can be managed without narcotics, they can usually resume driving and other daily tasks.

Reliable urinary function: patients frequently express concerns about incontinence. Twenty years ago, some 10 percent of patients were left incontinent by prostate surgery. Because we are now able to better protect the nerve bundles and urinary sphincter during surgery, 98 percent of patients do not need pads one year after surgery.

A healthy sex life: while measuring sexual potency is subjective, I advise patients that if they are potent before surgery, theres a 75 to 90 percent chance they will remain potent after nerve-sparing surgery.

Managing treatment: traditional radiation treatments can require up to 6 weeks of daily hospital visits, a burdensome task for patients who are trying to hold down a job. Hyperfractionated radiotherapy uses higher doses of radiation spread over fewer days, allowing patients to keep a regular work schedule. Ablation therapy requires even less of a time commitment.

Novel treatment strategies

Novel treatment like theranostics are on the rise. Theranostics combines therapeutic, radioactive pharmaceutical particles with diagnostic imaging to examine cancerous cells. In prostate cancer patients, a PSMA PET scan is done to evaluate for metastatic disease. PSMA, or prostate-specific membrane antigen, is expressed by virtually all prostate cancers and its presence locates the cancerous cells accurately. When these cells and receptors are located, a theranostic medicine such as Lutetium-177 in combination with PSMA is administered, which binds to and kills the cancerous cells. Its use is currently limited to prostate-specific membrane antigen-positive metastatic castration-resistant prostate cancer.

Training

As prostate cancer diagnoses continue to rise, todays physicians have a duty to prepare the next generation in the fight. Miami Cancer Institute, in concert with Florida International Universitys Herbert Wertheim College of Medicine, offers a two-year Urologic Oncology fellowship covering all treatment modalities.

We also work with Year 3 and 4 medical students who havent yet chosen a specialty. Its my job to introduce them to the challenges of our super-specialty and pique their interest in pursuing urologic oncological surgery.

Lastly, we support working physicians who desire to continue their education in the specialty. My colleagues and I offer surgical observation opportunities for local physicians as well as participate in international training programs.

The advent of teleconferencing has created exciting new training opportunities. We offer bimonthly telemedicine webinars through Baptist Urological Academy to an international audience. Many participating physicians and fellows become recognized urologic oncologists in their own countries.

Managing prostate cancer starts with screening and early diagnosis but extends into the effective management of prostate cancer. It requires constructive participation of all involved in the prostate cancer management including the government, health institutions, physicians, health care staff and most importantly, the patients.

REFERENCES

1, Siegel RL,Miller KD,Wagle, NS,and Jemal A, A.Cancer statistics, 2023.CA Cancer J Clin2023;73(1):17-48. doi:10.3322/caac.21763

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Rise in Prostate Cancer Cases Contributes to Challenges in Care - Targeted Oncology

When to Use Second-Line CAR T-cell Therapy for Relapsed … – Targeted Oncology

Gilles Salles, MD

Chief of Lymphoma Service

Steven A. Greenberg Chair

Memorial Sloan Kettering Cancer Center

New York, NY

Targeted OncologyTM: How do the National Comprehensive Cancer Network (NCCN) guidelines recommend treating patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) based on the outcomes of first-line therapy?

SALLES: [Looking at] the NCCN guidelines, for patients with the intention to proceed to autologous stem cell transplant (ASCT), second-line therapy is divided by complete responders with ASCT, partial responders [who] usually go to CAR [chimeric antigen receptor] T-cell therapy, and those with progressive disease who will go to salvage therapy or CAR T-cell therapy.1 Patients with relapsed disease within 12 months, or primary refractory disease, should envision CAR T-cell therapy and the nontransplant candidates will go to a couple of suggested regimens.

If we go back to those patients with the intention to treat with CAR T-cell therapy, we have to think of patients a little differently from [the way one is] used to thinking. Were used to seeing patients [in terms of being] eligible or ineligible for ASCT. [Now,] for these [patients relapse] early, [we have to ask if they] are eligible for CAR T-cell therapy and decide who is more [optimal] for CAR T-cell therapy. Thats probably a good discussion [to have]. In this case, we have both axicabtagene ciloleucel [axi-cel; Yescarta] and lisocabtagene maraleucel [liso-cel; Breyanzi] available for patients.

At what point can CAR T-cell therapy be used for patients with relapsed/refractory DLBCL?

Regarding their [FDA] approvals, axi-cel was approved for patients who are refractory to first-line therapy or relapse within 12 months of first-line chemoimmunotherapy.2 The way we all interpret that is 12 months from the end [of first-line therapy], though initially some of the trials [did otherwise]. Liso-cel has a slightly different label: refractory disease or first-line relapse within 12 months of first-line therapy, then there is an addendum which is based on the study: refractory disease to first-line chemoimmunotherapy or relapsed after first-line chemoimmunotherapy and not eligible for ASCT.3

For axi-cel, the ZUMA-7 trial [NCT03391466] was taking patients from the time of relapse, [performing] apheresis on the patient, bridging them with steroids but not with chemotherapy, which may make [a difference].

What were the efficacy outcomes of the phase 3 trials investigating second-line CAR T-cell therapy?

[There were] 3 trials [of CAR T-cell therapy for DLBCL], ZUMA-7, BELINDA [NCT03570892], and TRANSFORM [NCT03575351].4-6 Patients were in the range of 55 to 60 years of age [on these trials]. They had the same criteria of eligibility; all these patients [relapsed after] less than 12 months. In ZUMA-7, the only bridging therapy was steroids whereas BELINDA, the one with tisagenlecleucel [tisa-cel; Kymriah] and TRANSFORM with liso-cel were offering the possibility of 2 or 3 cycles of chemotherapy as bridging therapy.

Two-thirds to three-quarter of patients were refractory, [and approximately] 25% were relapsed [across these studies]. The median follow-up was quite different; [approximately] 2 years for ZUMA-7, 10 months for BELINDA, and 6 months at the time of publication of TRANSFORM. The complete response [CR] rate to CAR T-cell therapy in ZUMA-7 was 65%, and the CR rate with ASCT was 32%.4 With BELINDA there were no difference between the 2 groups, a CR of 28% [in each arm],5 and with TRANSFORM [the liso-cel had a] 66% CR rate which is identical to ZUMA-7 and 39% with ASCT.6

Two of the studies were positive, the third one is negative. If you want to know why is the third one was negative, is it a question of product, is it a question of trial design, is it a question of delays in manufacturing the product? I think there were many explanations raised. I personally think there was not one single explanation; it was a mixture of different explanations. Tisa-cel [is an effective] primary CAR T-cell therapy for children with acute lymphoblastic leukemia, so its a good [therapy], but in this DLBCL setting it may be inferior, and there are some data from a registry study coming from [France] suggesting that it is inferior to axi-cel.7

[For ZUMA-7, the PFS [progression-free survival] rate at 24 months was 46% for axi-cel versus 27% for ASCT.4 In BELINDA [PFS data were] not provided, [so PFS in both arms were] not reached,5 and [for TRANSFORM] we have a 12-month PFS rate of 50% vs 33%, so a highly significant difference for 2 [of these trials].6 So its a significant change for early relapse, and potentially for later [relapse].

REFERENCES

1. NCCN. Clinical practice guidelines in oncology. B-cell lymphomas, version 2.2023. Accessed March 23, 2023. https://bit.ly/3TEXEqA

2. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA. April 1, 2022. Accessed March 23, 2023. https://bit.ly/3ngfNPF

3. FDA approves lisocabtagene maraleucel for second-line treatment of large B-cell lymphoma. News release. FDA. June 24, 2022. Accessed March 23, 2023. https://bit.ly/3TBFcPE

4. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133

5. Bishop MR, Dickinson M, Purtill D, et al. Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma. N Engl J Med. 2022;386(7):629-639. doi:10.1056/NEJMoa2116596

6. Kamdar M, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399(10343):2294-2308. doi:10.1016/S0140-6736(22)00662-6

7. Bachy E, Le Gouill S, Di Blasi R, et al. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma.Nat Med. 2022;28(10):2145-2154. doi:10.1038/s41591-022-01969-y

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When to Use Second-Line CAR T-cell Therapy for Relapsed ... - Targeted Oncology

Improving Multiple Myeloma Diagnosis with Advanced Treatments – News18

Multiple myeloma is a type of blood cancer that affects the plasma cells, which are responsible for producing antibodies in the body. Being one of the most common blood cancer, it requires timely diagnosis and treatment. Over the years, there have been many advances in the diagnosis and treatment of multiple myeloma, leading to better outcomes for patients.

Plasma cells, a subset of white blood cells that make antibodies, are the target of the malignancy known as multiple myeloma. Early diagnosis and treatment of multiple myeloma are crucial for improving outcomes and enhancing chances of survival," says Dr S Jayanthi, Senior Pediatric Oncologist, Kamineni Hospitals, Hyderabad.

The latest treatment approaches to enhance the chances of diagnosing multiple myeloma are offering promising new treatments. Many multiple myeloma patients receive chemotherapy in order to reduce or eliminate their cancer cells. In some cases, chemotherapy may also lead to cancer remission. However, long term cancer control can often be difficult to achieve with this approach alone. Allogeneic bone marrow transplantation is a new treatment option that has shown promise for many multiple myeloma patients and is considered a more aggressive approach than just chemotherapy alone," adds Dr Jayanthi.

Early diagnosis and treatment of multiple myeloma are essential for improving outcomes and enhancing chances of survival. The latest treatment approaches, such as advanced imaging tests, biopsy, genetic testing, targeted therapies, and immunotherapy, can help to diagnose multiple myeloma and provide personalized treatment plans for better outcomes.

Advancements in imaging technology, such as PET-CT and MRI scans have allowed for more precise assessment and can detect myeloma lesions earlier than traditional X-rays, which can be critical for early diagnosis and effective treatment. Another newer advance in the treatment of multiple myeloma is the use of precision medicine. Precision medicine involves using genetic testing to identify the specific genetic mutations that are driving the growth of myeloma cells. Once these mutations are identified, targeted therapies can be used to block their effects and stop cancer from growing. This approach can lead to more personalized and effective treatment for each individual patient," says Dr Ashish Dixit, Consultant, Haematology, Haemato Oncology & Bone Marrow Transplantation, Manipal Hospital Old Airport Road.

Targeted therapies are newer treatment options for multiple myeloma. These drugs are designed to target specific proteins or pathways that are essential for the growth and survival of myeloma cells. An example of targeted therapy for multiple myeloma can be proteasome inhibitors, such as bortezomib. These drugs block the breakdown of proteins in myeloma cells, leading to their death.

Another newer treatment option for multiple myeloma is monoclonal antibodies, which are designed to target specific proteins on the surface of myeloma cells. Daratumumab is an example of a monoclonal antibody used in treating multiple myeloma. This drug helps the immune system recognize and attack myeloma cells more effectively," adds Dr Dixit.

Stem cell transplantation is one of the standard treatments for multiple myeloma. Stem cell transplantation involves collecting healthy stem cells from the patient or a donor, and then administering high doses of chemotherapy to kill cancer cells. The healthy stem cells are then infused back into the patients body, helping to restore the immune system and blood cell production.

Targeted Immunotherapy is a treatment option that uses the bodys immune system to fight cancer cells. One type of immunotherapy used in multiple myeloma is called CAR T-cell therapy. This treatment involves modifying the patients own T-cells in a laboratory so that they can recognize and destroy myeloma cells more effectively," opines Dr Dixit.

These newer advances in the diagnosis and treatment of multiple myeloma offer hope for patients with this disease. With continued research and development, we may see even more effective treatments in the future. It is important for patients with multiple myeloma to work closely with their doctors to determine the best course of treatment for their individual needs.

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Actor Sam Neill ‘very well’, back working, as rare, aggressive cancer … – Stuff

LAWRENCE SMITH/Stuff

Sam Neill is back working, despite rare cancer diagnosis.

Kiwi actor Sam Neill, who revealed he has been receiving treatment for a rare form of blood cancer, is very well and back at work.

Neills personal assistant Lauren Folk Major thanked the fans for their support after he told the Guardian he is being treated for angioimmunoblastic T-cell lymphoma (AITL).

He is very well and back at work starring opposite Annette Bening in the upcoming limited series, Apples Never Fall, said Falk Major.

Neill is releasing a memoir on Tuesday titled Did I Ever Tell You This?.

READ MORE:* Kiwi actor Sam Neill says he's being treated for blood cancer* Sam Neill says Michael Fassbender 'took offence' at having a rooster named after him* Peter Rabbit director spills the berries on Kiwi actor Sam Neill* Sam Neill eats plastic bag to save turtles

Neill told the Guardian his book is not a cancer memoir, but rather his illness forms what he calls a spiral thread throughout the story.

I cant pretend that the last year hasnt had its dark moments, he said. But those dark moments throw the light into sharp relief, you know, and have made me grateful for every day and immensely grateful for all my friends. Just pleased to be alive.

What is angioimmunoblastic T-cell lymphoma?

Leukaemia and blood cancer New Zealand says lymphomas are a relative common form of cancer in Aotearoa-New Zealand, affecting about 800 Kiwis every year. There are more than 50 kinds of lymphoma, some are very rare.

The cancer Neill is receiving treatment for is a rare, often aggressive, or fast-growing, form of lymphoma.

This is one of a number of cancers that attack the immune system via the lymph nodes. The lymphatic system filters lymphatic fluid and white blood cells around the body, helping your body fight disease.

While non-life-threatening illnesses such as strep throat and chickenpox can cause our lymph nodes can swell, swelling can also, on rare occasions, signal the presence of cancer.

There are two types of Lymphoma: Hodgkins and Non Hodgkins, the chief difference being which kind of lymphocyte, or white blood cell, the cancer attacks. Cancer Research UK describes AITL as a non-Hodgkins Lymphoma that affects the T-cells, which fight infection. Because it affects the T-cells, AITL can impact organs beyond the lymphatic system.

Governor General of New Zealand/

Dame Cindy Kiro confers Sam Neill as a Knight Companion of the New Zealand order of Merit.

Symptoms can include fevers, night sweats, skin rashes, and a form of anaemia, which results from the bodys immune system attacking its own cells and tissues.

The Lymphoma Research Foundation says diagnosis is most commonly by biopsy, and PET and MRI scans. Treatment is with corticosteroids, such as prednisone, and chemotherapy. Some research shows stem-cell therapy has encouraging outcomes.

According to his book, Neills lymphoma responded to a new drug therapy after chemo failed the first time round. His cancer is now in remission.

Kiwi actor and winemaker Sir Sam Neill, of Jurassic Park and The Piano fame, is the proprietor of Two Paddocks, a family vineyard based in Central Otago. He talks about the country's unique wine.

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Actor Sam Neill 'very well', back working, as rare, aggressive cancer ... - Stuff

Pets Plus Us Pet Health Insurance Review 2023 Forbes Advisor … – Forbes

To find the best pet insurance we reviewed each companys policy wording and used data provided by PetInsurer.com to score each pet insurance company based on the following:

Pet insurance rates: 40% of score. We calculated average rates for plans with $5,000 or unlimited coverage, a $100 deductible and an 80% reimbursement level, or the closest options available.

Special waiting period: 10% of score. Many pet insurance companies have a special waiting period for problems such as cruciate ligament issues and hip dysplasia. Plans that had no waiting period, a waiting period of six months or less, or the ability to have the waiting period waived scored higher.

Direct payment to vet: 10% of score. Pet insurance companies that have the ability to pay a vet directly earned points.

24/7 vet health line: 10% of score. Insurers that provide access to a 24/7 vet health line scored in this category.

Routine wellness plans: 10% of score. Insurers that offer wellness plans, either included with a plan or as a rider, earned points.

Dental coverage for illness: 10% of score. While most insurers cover dental accidents, not all insurers cover dental illnesses, such as gum disease or cleanings. Plans with more extensive dental coverage scored higher.

Pet ownership assistance: 5% of score. Insurers that include coverage for pet owner expenses, such as advertising and reward for lost pets, boarding for medical emergencies, end of life expenses and/or vacation cancellation, scored in this category.

Any discount: 5% of score. Insurers that offer any kind of discount, including a multi-pet discount, healthy pet discount, loyalty discount, etc., earned points.

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Pets Plus Us Pet Health Insurance Review 2023 Forbes Advisor ... - Forbes

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