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Dr. Dinesh Raj Neupane is a public health pharmacist. He obtained his degree in Public Health at Tribhuvan University, Institute of Medicine, Maharajgunj Medical Campus, in Kathmandu.

Breast cancer care differs around the world, revealing urgent unmet needs in Nepal, where access, support, and treatment remain out of reach for many.

Layers of Pain: Decoding the Multifaceted Toxicity of Breast Cancer 

Use of the NeuroSAFE technique technique, where tissue is examined during prostate cancer surgery, nearly doubled the number of patients who had no or mild erectile dysfunction approximately a year later, researchers have found.

Findings from the NeuroSAFE PROOF phase 3 trial, conducted at five National Health Service hospitals in the United Kingdom, were published in 

 and presented at the 40th Annual European Association of Urology Congress in Madrid, with researchers reporting on the use of NeuroSAFE to guide nerve sparing during robot-assisted radical prostatectomy (RARP).

In 344 patients who underwent radical prostatec- tomy, or the surgical removal of the prostate (173 patients in the NeuroSAFE group and 171 in the standard RARP group) at a median follow-up of 12.3 months, 39% and 23% of patients, respectively, had no or mild erectile dysfunction.

CURE spoke with NeuroSAFE PROOF researcher 

 about the study and its findings. Shaw is the lead for robotic urology for University College London Hospitals and a professor of urology at University College London.

CURE: What do you hope is the big takeaway from these findings?

 The trial that we presented in Madrid, that coincided with the Lancet Oncology paper, is definitive evidence that the new technique that we trialed, the NeuroSAFE technique, allows us to help more men get back to potency after radical prostatectomy. Radical prostatectomy, some of you will probably be aware, is an operation used to cure prostate cancer. It's really good for curing prostate cancer, but many men are left with side effects, urinary incontinence and erectile problems. And using this technique, we doubled the number of men who were able to get normal erections after the procedure compared to our standard approach.

How does the NeuroSAFE technique supplement or how is it different than the current standard of care?

It's an additional step to the operation, and it's performed during the operation whilst the patients asleep. It's designed because when we do a prostatectomy, we want to take away all the cancer and leave behind all of the important structures that surround the prostate, but they're really closely approximated. So, the prostate is a bit like an onion. It's got concentric layers running around it, and within the outer layers are the very small, microscopic nerves that send the signals for men to get erections. So where we can we peel those layers off, we leave them inside the patient, so they remain functional. And that's OK if the tumor is away from where the nerves are, but if it's close to the edge, and as it stands, we don't have a way of accurately telling us, even MRI scanning doesn't tell us exactly where the cancer finishes and the nerves are, so to a certain extent, we err on the side of caution. And sometimes we find we've taken a prostate out with the outer coverings, not done nerve sparing, whereas actually we could have done nerve sparing, and that's due to the lack of resolution on the MRI scans, it doesn't give you that sub-millimeter measure of how close you might or how far you might be from the nerves.

So this technique is designed to deal with that problem. It gives the surgeon feedback during the operation. So the approach is you do a full nerve spare, regardless of what the MRI scan looks like, and then when the prostate is removed from its attachments, it can be brought out from the inside of the patient and analyzed, and we look at the edge of it, and there's quite an involved process. It's called frozen section. We freeze the tissue, slice it super thin, and then stain it so that it can be examined by a pathologist. And if the pathologist tells you that there's cancer at the edge here, that's not good. OK, we we now need to take the nerves away, and we do that at the same sitting during the same operation. So it adds about an hour on to the patient's surgery. The patient is asleep during that time, but it allows us this control, this extra bit of information, [to determine] has nerve sparing been safe in this patient or not.

Did anything in these results surprise you and your colleagues?

I think we were optimistic that we were going to see an effect, but perhaps surprised to see that the effect was quite so marked: twice as many men a year after surgery, either with no erectile dysfunction or mild erectile dysfunction. And that's quite important, because we treat many, many men with prostate cancer. Some of them are young. The age at which we start worrying about prostate cancer is 50 in Caucasian men, 45 in patients who have relatives with prostate cancer or Afro Caribbean men.

So some of these patients are young, and it's one thing saying to a 70-year-old man who's not particularly sexually active, "You're not going to get erections again." But you tell that to someone who's 45 years old, who's maybe not in a stable relationship, that's life changing, and they've got the rest of their life to live with that. So this is really important for younger patients, sexually active patients, but particularly patients who were the conventional methods are used, MRI scanning, looking at the biopsy results, where it's felt they can't have nerve sparing, because there's a question about whether it would be safe or not,

How should these findings inform conversations that patients have with their doctors?

I think patients should be asking their doctors if they offer NeuroSAFE and discussing the relative merits of it. There are technical issues with running it. It takes a lot of coordination. It takes a team of people to prepare the slides. You've got to have a pathologist available to make the interpretation, make the call that the surgeon acts on. So I think we will see this being taken up by more centers with time. Some centers can't do it either because of geography, maybe the pathologist is not in the same building as the as the surgery. That becomes a real issue when you're talking about transferring tissue samples. But there's some new technology out there that's quite exciting. There's something called a confocal laser microscope, which gives it a similar readout. It scans the whole surface of the prostate, and that image can then be beamed to a pathologist. They might be miles away. They might be around the other side of the world. The Internet is so quick now, and the pathologist can make a call on that image.

So, I think this calls for an increase in our performing an examination of the prostate to guide nerve sparing during surgery. The practicalities of that will vary by hospital, by geography, but I think many more surgeons will be making an effort to gather this extra bit of information that clearly makes a difference to patients.

“Effect of NeuroSAFE-guided RARP versus standard RARP on erectile function and urinary continence in patients with localised prostate cancer (NeuroSAFE PROOF): a multicentre, patient-blinded, randomised, controlled phase 3 trial” by Eoin Dinneen et al., 

Transcript has been edited for clarity and conciseness.

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The NeuroSAFE technique, used during prostate cancer surgery, significantly improves erectile function outcomes post-surgery. The NeuroSAFE PROOF phase 3 trial demonstrated that this technique nearly doubled the number of patients experiencing no or mild erectile dysfunction a year after surgery compared to standard procedures. This technique involves intraoperative analysis of prostate tissue to guide nerve sparing, enhancing surgical precision. While promising, its implementation requires coordination and resources, including pathologist availability. The findings suggest a potential shift in surgical practices to improve quality of life for prostate cancer patients.

Use of NeuroSAFE during prostatectomy nearly doubled the number of patients who had no or mild erectile dysfunction approximately a year later.

Tumor

NeuroSAFE May Preserve Erectile Function After Prostate Cancer Surgery

Among patients with advanced castration-sensitive prostate cancer, health-related quality of life was not statistically different between those receiving Erleada (apalutamide) alone or in combination with Zytiga (abiraterone acetate) and prednisone compared with those receiving androgen-deprivation therapy (ADT) plus Zytiga and prednisone, according to findings in 

Health-related quality of life was evaluated using the Functional Assessment of Cancer Therapy–Prostate (FACT-P) questionnaire and its subscales. The questionnaire was completed at baseline and every four weeks until week 25. FACT-P scores range from 0 to 156, with higher scores indicating better quality of life, according to study authors.

There were no significant differences in baseline mean FACT-P total scores or subscales across the three treatment groups: ADT plus Zytiga and prednisone, 118.5; Erleada, 116.1; and Zytiga and prednisone plus Erleada, 114.9.

Health-related quality of life was maintained during the treatment period, with no statistically significant differences at 25 weeks in mean FACT-P total scores or subscales: ADT plus Zytiga and prednisone, 122.3; Erleada monotherapy, 119.5; and Zytiga and prednisone plus Erleada, 119.9.

The Erleada monotherapy and Zytiga and prednisone plus Erleada groups did not experience meaningful improvements in health-related quality of life compared with the ADT plus Zytiga and prednisone group, except in time to deterioration of the emotional well-being score. This outcome was more favorable in those who received Erleada alone, with a 63% reduction in risk compared with the ADT plus Zytiga and prednisone group, which had a 44% reduction in risk.

A prostate-specific antigen level of 0.2 nanograms per milliliter or lower at week 25 was observed in 31 of 41 patients (75.6%) in the ADT plus Zytiga and prednisone group, 24 of 40 patients (60%) in the Erleada monotherapy group and 31 of 39 patients (79.5%) in the Erleada plus Zytiga and prednisone group. The two-year overall survival rates were 92.5% for the ADT plus Zytiga and prednisone group, 87.9% for the Erleada monotherapy group and 92.7% for the Erleada plus Zytiga and prednisone arm.

Treatment-related side effects of any grade were reported in 30 of 42 patients (71.4%) in the ADT plus Zytiga and prednisone group, 34 of 42 patients (81%) in the Erleada monotherapy group and 36 of 44 patients (81.8%) in the Erleada plus Zytiga and prednisone group.

Grade 3 (severe) and 4 (life-threatening) treatment-related side effects occurred in eight of 42 patients (19%) in the ADT plus Zytiga and prednisone group, seven of 42 patients (16.7%) in the Erleada monotherapy group and 10 of 44 patients (22.7%) in the Erleada plus Zytiga and prednisone group. Lower rates of hot flashes and hypertension were reported in patients who received Erleada monotherapy.

Gynecomastia affected 23 of 42 patients (54.8%), and breast pain was reported by six of 42 patients (14.3%) in the Erleada monotherapy group, both higher than rates observed in the other two groups. No new safety signals were detected in
the study.

“Androgen Receptor Pathway Inhibitor Therapy for Advanced Prostate Cancer: Secondary Analysis of a Randomized Clinical Trial” by Dr. Diogo Assed Bastos et al., 

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In patients with advanced castration-sensitive prostate cancer, health-related quality of life (HRQOL) was similar across treatment groups receiving Erleada (apalutamide) alone, APA plus Zytiga (abiraterone acetate) and Deltasone (prednisone), or ADT plus AAP. The study, published in JAMA Network Open, found no significant differences in HRQOL scores at 25 weeks. However, the APA-alone group showed a more favorable time to deterioration in emotional well-being. PSA levels and overall survival rates were comparable, with varying side effect profiles across treatment groups.

A study found no significant HRQOL differences between Erleada-based therapies and ADT plus AAP for advanced castration-sensitive prostate cancer.

Erleada Combo Shows Comparable Quality of Life Outcomes in Prostate Cancer

In a real-world setting, standard-of-care Carvykti (ciltacabta-gene autoleucel) has been shown to elicit responses from nearly all participating patients with relapsed/ refractory multiple myeloma (R/R MM).

Carvykti is a type of chimeric antigen receptor-T (CAR-T ) cell therapy, which, as explained by the National Cancer Institute, involves a patient’s T cells — part
of the immune system — being extracted, changed in a laboratory to attack cancer cells, grown in the laboratory and infused back into the patient.

Overall and complete response rates were 89% and 70%, respectively, in
all patients who received Carvykti, 94% and 74% in 191 patients who received conforming Carvykti and 95% and 76% in 152 patients treated with conforming Carvykti with fludarabine/ cyclophosphamide lymphodepletion.

A comforming treatment is administered according to the specifications of
the FDA’s approval, and lymphodepletion is a short course of chemotherapy administered before CAR-T cell therapy.

 for adults with R/R MM who had received at least four prior lines of treatment. In 2024, the agency approved Carvykti for patients who received at least one prior line of therapy.

, that led to the FDA’s 2022 approval of Carvykti, the overall response rate was 98%, with 83% stringent complete response, according to findings published in 2023.

Patients with R/R MM who underwent leukapheresis, or the collection of healthy white blood cells from a patient, for Carvykti manufacturing at 16 American academic medical centers were included in the study, published in Blood, with 255 patients undergoing leukapheresis and 236 receiving Carvykti.

Of the real-world patients, 54% would not have met the eligibility criteria for CARTITUDE-1.

Senior author Dr. Doris K. Hansen of Moffitt Cancer Center’s Department
of Blood and Marrow Transplant and Cellular Immunotherapy, explained in an interview with 

 why such real-world findings are significant.

“Clinical trials are invaluable because they serve as the gold standard for introducing new therapies and advancing science,” Hansen explained.

“However, clinical trials often have strict eligibility criteria. Patients must meet very specific criteria to participate — they need to have good organ function, stable blood counts and no significant comorbidities."

In contrast, Hansen said, the patients seen in day-to-day clinical practice often have a variety of health challenges, with many patients having comorbid conditions like cardiac issues or renal impairment, and with about 20% of those diagnosed with myeloma experiencing kidney problems. “Additionally,” Hansen said, “some patients may have plasma cell leukemia, amyloidosis or myeloma-related bone damage, which can lead to fractures, pain and even reduced mobility or wheelchair use. These factors often make patients ineligible for clinical trials. ... It is, therefore, very important to report on the experiences of these patients. By studying their outcomes, we can understand how treatments perform in real-world scenarios, as opposed to the controlled, ideal conditions of clinical trials.”

The eligibility criteria for CARTITUDE-1 included adequate organ function, limited comorbidities and having no prior exposure to B-cell maturation antigentargeted therapy.

Cytokine release syndrome was experienced by 75% of patients, with grade 3 (severe) or higher in 5%. Immune effector cell-associated neurotoxicity syndrome was seen in 14%, with grade 3 or higher in 4%. Delayed neurotoxicity was reported in 10% of patients.

Researchers reported a 10% nonrelapse mortality rate, mostly from infections, and noted that second primary malignancies, excluding nonmelanoma skin cancers, were seen in 5.5% of patients and myeloid malignancies/acute leukemia in 1.7%.

 such as Carvykti, as explained by the National Cancer Institute, involves a patient’s T cells, part of the immune system, being extracted, changed in a laboratory to attack cancer cells, grown in the laboratory and infused back into the patient. Carvykti is currently approved by the FDA to be administered in the second line of treatment.

Safety and Efficacy of Standard of Care Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma” by Dr. Surbhi Sidana, et al., 

Carvykti (ciltacabtagene autoleucel) demonstrates significant efficacy in real-world settings for relapsed or refractory multiple myeloma, with 89% of patients responding and 70% achieving complete response. Despite many patients not meeting clinical trial criteria, outcomes were comparable to the CARTITUDE-1 trial. At 13 months, median progression-free survival and overall survival were not reached, with 12-month estimates at 68% and 82%, respectively. Side effects included cytokine release syndrome and neurotoxicity. Carvykti, a CAR-T cell therapy, is FDA-approved for patients with multiple prior treatments.

The CAR-T cell therapy Carvykti has been shown to be effective among patients outside the confines of a clinical trial.

Carvykti Effective in Real-World Setting for Myeloma 

Among patients with stage 3 unresectable non-small cell lung cancer (NSCLC), the first participant has been dosed in the phase 2 CONVERGE study, according to a news release from biotechnology company Nanobiotix. The randomized, controlled clinical trial is evaluating the potential first-in-class radioenhancer JNJ-1900 (NBTXR3) in patients being treated with standard-of-care chemoradiation followed by consolidation Imfinzi (durvalumab).

“We believe the true value of [NBTXR3] is driven by its potential to address the unmet needs of the millions of patients each year who receive radiotherapy as part of their treatment,” said Laurent Levy, Chief Executive Officer and Chairman of the Executive Board at Nanobiotix. “With a clear path to potential registration in head and neck cancer established through NANORAY-312, the first patient dosed in the CONVERGE study in [non-small cell lung cancer] NSCLC brings us another step closer to delivering for the large number of patients [NBTXR3] is designed to serve.”

Who is Eligible For CONVERGE Study Enrollment?

According to the clinical trial page
at clinicaltrials.gov, CONVERGE is evaluating the addition of NBTXR3 to concurrent platinum-based doublet chemotherapy with radiation therapy, followed by consolidation immunotherapy, and whether this enhances the objective response rate in patients with locally advanced, unresectable stage 3 NSCLC.

To be considered eligible for enrollment, patients must be candidates for chemotherapy with radiation therapy; have a pathologically confirmed NSCLC diagnosis within three months prior to enrollment; present with unresectable stage 3IIIA or 3IIIB NSCLC; have at least one target lesion suitable for intratumoral or /intranodal injection and external beam radiation therapy; and have an ECOG performance status of 0 or 1.

Participants are considered ineligible for enrollment in the study if they have a history of primary immunodeficiency; organ transplantation requiring immunosuppression; significant cardiac events within three months before enrollment; concurrent or recent malignancies other than NSCLC; and known hypersensitivity to study drugs or components.

Patients with active bleeding diathesis or patients requiring anticoagulation or antiplatelet therapy that cannot be safely modified for procedures are also excluded.

The novel, potentially first-in-class oncology product NBTXR3 comprises functionalized hafnium oxide crystal nanoparticles administered via one-time intratumoral injection and activated by radiotherapy. The proof-of-concept for NBTXR3 was demonstrated in soft tissue sarcomas, leading to the agent receiving a European CE mark in 2019.

The agent’s mechanism of action is designed to induce substantial tumor cell death within the injected tumor when activated by radiotherapy, thereby triggering an adaptive immune response and establishing long-term anticancer memory. Consequently, the company anticipates that NBTXR3 could be applied to any solid tumor treatable with radiotherapy and be adaptable to any therapeutic combination, especially with immune checkpoint inhibitors.

The radiotherapy-activated NBTXR3 is under evaluation for multiple solid tumor indications as a stand-alone treatment and in combination with anti-PD-1 immune checkpoint inhibitors. These initiatives include the global, randomized NANORAY-312 trial, which is focused on locally advanced head and neck squamous cell carcinomas. In February 2020, the Food and Drug Administration granted fast track designation to NBTXR3 activated by radiotherapy, with or without Erbitux (cetuximab), for patients with locally advanced head and neck squamous cell carcinoma who are ineligible for platinum-based chemotherapy.

In 2019, the company entered a comprehensive clinical research partnership with The University of Texas MD Anderson Cancer Center to sponsor multiple phase 1 and 2 trials evaluating NBTXR3 across various tumor types and therapeutic combinations. Nanobiotix announced a license agreement with Janssen Pharmaceuticals, a Johnson & Johnson company, for the global co-development and commercialization of NBTXR3 in 2023.

The phase 2 CONVERGE study has commenced dosing its first participant to evaluate the radioenhancer JNJ-1900 (NBTXR3) in stage III unresectable non-small cell lung cancer (NSCLC) patients. This trial investigates the efficacy of NBTXR3 combined with standard chemoradiation and consolidation durvalumab. NBTXR3, a hafnium oxide nanoparticle, is activated by radiotherapy to induce tumor cell death and an adaptive immune response. The study aims to enhance objective response rates in NSCLC, with eligibility criteria including specific NSCLC stages and performance status, while excluding certain medical conditions.

The first participant has been dosed on the phase 2 CONVERGE study evaluating NBTXR3 in stage III, unresectable non–small cell lung cancer.

Breaking Down the CONVERGE Study of NBTXR3 in Stage 3 Unresectable NSCLC

The woman who raised me and I did not always see eye to eye. In fact, as two stubborn, opinionated characters we frequently bickered, challenged and exchanged choice words with one another. 

As I reflect on 25 years strong with Mom, here are some of my favorite words that we exchanged. We gave each other many cards over the past few years, one of which she had told me she looked for a long time searching for the right message to express her feelings. It reads:

"When you have a daughter who makes you proud, makes you laugh and, very often, makes your day ... you know what joy is. When you have a daughter who is a good person with a gracious heart and generous spirit ... you know what peace is. When you have a daughter whose beauty (inside and out) is matched only by her compassion for others ... you know what love is. Because I have you for my daughter, I know what it is to be truly blessed."

When I first read those words — as I read them now — I feel so close to my mom. Recently, I found a card with the words that expressed how I feel about her. I read this aloud to her on Christmas Day.

"Dear Mom, I'm so grateful for the way I was raised. You were never afraid to be my mother — to put your foot down, to teach me right from wrong, to make sure I did my best. You always let me know I had a mama who cared about me, who believed in me, who was there for me no matter what. Growing up with that kind of love and support made such a difference in my life; it made me who I am today."

My mother was never afraid to voice her opinion or be one to mince words, to put it lightly; but she was always pure in her intentions and true in her actions, and I feel so clearly, so humbly loved. As I go forward, I remember her strength and purity, her fierce sense of pride, her generous heart and sensitivity, her sense of humor (she once packed me a peanut-butter-jelly-and-ham sandwich because I refused to pick one of the two). 

Throughout her life and especially in her fight against lung cancer, Mom set us an example in unconditional devotion, taught our family valuable life lessons and never lost her indomitable spirit.

I know Mom is with us now and always. Goodbyes are only for those who love with their eyes, because for those who love with heart and soul there is no such thing as separation. I love you Mom, Happy New Year. Rest in peace and God bless.

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The narrative reflects on a complex yet deeply loving relationship between a daughter and her mother, characterized by mutual respect and understanding despite frequent disagreements. The daughter cherishes the heartfelt words exchanged through cards, highlighting the mother's pride, love, and unwavering support. The mother, who battled lung cancer, exemplified strength, devotion, and humor, leaving a lasting impact on her family. The daughter expresses gratitude for her upbringing and acknowledges the enduring connection with her mother, emphasizing that true love transcends physical separation.

A Tribute to Mom

Dr. Andre Henri Goy shared how CAR T-cell therapy led a retired pilot with lymphoma into remission, showing the impact of personalized treatment decisions.

CAR T-Cell Therapy Leads to Remission in Retired Air Force Pilot With Lymphoma 

Dr. Andre Henri Goy of John Theurer Cancer Center shared the story of a patient with lymphoma who achieved remission after CAR T-cell therapy, illustrating how individualized treatment decisions can lead to long-term outcomes and renewed quality of life.

Goy described how a patient named Mark Daniel first came to him nearly two decades ago with low-grade lymphoma. Daniel responded well to an immunotherapy-based clinical trial and remained active for years — flying planes, exercising daily and staying in great shape.

Years later, Daniel returned with a very aggressive lymphoma. Given the intensity of chemotherapy needed and the patient’s age, CAR T-cell therapy became the most appropriate option. After some complications from initial chemotherapy, Goy convinced Daniel to undergo CAR T-cell therapy, which led to a full recovery and sustained remission. He is now back in the air performing aerobatic flying.

Goy highlighted the importance of tailoring therapy to the patient, noting that CAR T-cell therapy can be especially valuable for individuals with aggressive disease who may not tolerate traditional options. “If we can give back and help them have a better life, it’s a good thing,” he said.

Goy serves as physician in chief of Oncology Care Transformation Services at Hackensack Meridian Health. He is also chairman and chief physician officer of John Theurer Cancer Center and leads the lymphoma division at the center’s location within Hackensack University Medical Center.

How do you determine when a patient is a good candidate for CAR T-cell therapy?

It’s a really important question. We'll take the example of Mark Daniel, because an example is really — well, obviously very important — and then we'll talk a little bit more generally about how we can make things better.

So, Mark Daniel came to see me almost 20 years ago with a low-grade lymphoma. At that time, he really didn’t want to get chemotherapy and qualified for a trial we had for patients receiving first-line therapy that was essentially immunotherapy — a combination that included Rituxan (rituximab) with a small molecule. He did really well — so much so that it sort of disappeared. This is an avid pilot, a retired pilot from the U.S. Air Force, a commercial pilot, still flying, doing aerobatic flying now, and at the gym every day. Amazing shape. Great guy.

He came to see me about two and a half, three years ago with a very aggressive new lymphoma — a very large mass in his abdomen causing pain. Initially, he thought this was because he overdid it with exercise. But we found the mass, and when we did a biopsy, it was a very high-grade, aggressive lymphoma.

Dr. Dinesh Raj Neupane

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