Latest news with #City of Hope
Medscape
5 days ago
- Health
- Medscape
Other GU Cancers Share Germline Mutation Rates Seen in Ovarian Cancer
This transcript has been edited for clarity. Hello. I'm Dr Maurie Markman, from City of Hope. I'd like to discuss a very interesting and controversial topic. The paper I'm discussing is 'Germline Pathogenic Variants Identified in Patients With Genitourinary Malignancies Undergoing Universal Testing: A Multisite Single-Institution Prospective Study,' published in the Journal of Urology . It has been well recognized for over a decade that patients with ovarian cancer need to have germline testing, independent of whether they have a family history of that particular cancer because we identified particular mutations — BRCA mutations, BRCA1 and BRCA2 — that may not be evident in the family by history but are very relevantpotentially for cascade testing of their family members later. Also, of course, in that setting, there are therapeutic implications for the use of PARP inhibitors. Increasingly, the discussion is about more universal testing for patients with breast cancer because of the incidences of BRCA and other mutations that are both relevant for treatment and for the question of genetic counseling for other members of the family. What about other tumor types? What about genitourinary (GU) cancers, as identified here? Should one take patients with all different kinds of GU tumors — prostate cancer, bladder cancer, kidney cancers, typically — and say there's a role for universal germline testing when a patient has been identified as having one of these cancers? To address this question, the group at the Mayo Clinic undertook comprehensive germline testing, examining for pathogenic germline variants at several sites from April 2018 to March 2020. This was a greater than 80-gene panel that was offered to patients. Today, that testing may be really quite different, but at that point it was greater than 80 genes that were tested for potential abnormality. A total of 601 patients enrolled with GU cancers. Again, this was across the sites and with GU cancers, regardless of a family history. There were 358 patients with prostate cancer, 106 with bladder cancer, and 137 with kidney cancer. Surprisingly, a majority of these patients, 86%, were male. Here is the important bottom line. Pathogenic germline variants, most with risk of high penetrance, were identified in 82 individuals, or 14% of the population. First, they were seen in almost the same percentage in kidney, bladder, and prostate cancer, and that 14% is not that far off. In fact, it's quite similar to the statement about ovarian cancer in terms of the overall population — 14% of the patients with GU cancer. Importantly, at this time, based on these data, fully 67% (or 2 of 3) patients had abnormalities that were potentially actionable. "Actionable" could mean a variety of things. It could mean there may be a therapy involved. It could mean that we need to talk to members of the family. They were not like, 'Oh, that's interesting, but there's nothing we can do about it.' For 2 out of 3, they could actually do something actionable. Importantly, of those 82 patients, 35% had at least one relative undergo cascade testing to examine for that variant. The bottom line here is that more than 1 of 8 patients in this unselected group of patients with GU cancers had a variant finding that was potentially pathogenic at the germline level. This would argue for — although there is going to be controversy and we need more data — universal testing, certainly of GU tumors, and one might ask for other tumor types. We need more data to confirm that. This would obviously be an extensive, new universal recommendation with costs associated with it, but this paper certainly raises that question that needs to be further examined. Thank you for your attention.
Medscape
14-07-2025
- Health
- Medscape
Metastases-Directed Therapy for Pancreatic Cancer
This transcript has been edited for clarity. Hello. I'm Dr Maurie Markman, from City of Hope. I'd like to discuss what I consider to be an absolutely fascinating paper, and one that I will say has very interesting results but raises many more questions than it answers. I think that was the intent of the authors. The paper is entitled, 'Addition of metastasis-directed therapy to systemic therapy for oligometastatic pancreatic ductal adenocarcinoma (EXTEND): a multicenter, randomized phase 2 trial,' published in the Journal of Clinical Oncology . You might ask what metastasis-directed therapy in pancreatic cancer means. Have we really made much of an impact on pancreatic cancer? In fact, in my earlier years of training, if somebody came up with the idea, or suggested as part of a trial or treatment of an individual patient, that they would focus on metastases in pancreas cancer, you might say they're crazy, or you might say: 'Yeah, but they probably don't know anything about the disease and its natural history.' Now, fast forward several decades. Even with the recognized, modest advances in systemic therapy, what we see are tremendous, really remarkable advances in innovations in radiation therapy. Of course, this includes not only the use of radiation itself but also the imaging technology that is used to direct the radiation therapy. These advances have permitted asking the questions that are addressed in the current study. Again, this study is fascinating. They randomized a very small number. Again, it's a randomized phase 2 study. It's really more of a proof of principle here. They randomized 41 patients with five or fewer metastatic lesions — with oligometastatic disease, they could have numerous lesions — to undergo what they've described as comprehensive metastases-directed therapy. Most of this was external beam radiation therapy and stereotactic radiation therapy, but there were some localized radiation implants as well, plus chemotherapy. This was comprehensive metastases-directed therapy to each of these sites plus chemotherapy vs chemotherapy alone. What was shown in this trial? The progression-free survival (PFS) in the metastases-directed therapy group was 10.3 months vs 2.5 months in the group of patients who received chemotherapy only, with a hazard ratio of 0.43 and statistical significance. Remember, this was a very small study, but we see more than a tripling in the PFS. There was no difference in overall survival, which is not at all surprising because it was a very small sample size. Very importantly — and essential to doing this trial ethically — a crossover was permitted at the time of progression, meaning that if a patient received chemotherapy only and progressed, they could potentially get stereotactic radiation to sites of metastatic disease. They might have also benefited from that kind of strategy to the metastasis-[therapy] so that overall survival in the small population may not be different. Again, there was a tripling of the time to disease progression. Clearly, a larger study will be required to be more definitive. We would need more centers involved and maybe some modification in the study design in this trial because of any issues that the investigators may have identified. Of course, overall survival would be a fair endpoint to look at, but again, crossover would be essential, and that might influence an ultimate is a very valid endpoint. The only other point to mention is, with these results — and as I mentioned, advances in radiation and imaging — is it reasonable to potentially consider this type of approach for individual patients as a component of aggressive standard of care? Of course, this would be with very adequate informed consent from patients, because we don't know what the impact will be. With the limited morbidity associated with the radiation, for an individual patient with pancreatic cancer who has an adequate performance status and limited metastases, if we give them chemotherapy and also directed radiation, is it reasonable to consider that as an appropriate treatment option outside the setting of a clinical trial? I think this is a very valid question that needs to be addressed. In my opinion, the answer in some settings should be yes, but that needs to be discussed much more widely than simply in this randomized phase 2 trial. Thank you for your attention.
