Avivit Peer

Background: Small cell carcinoma of the bladder (SCCB) is a rare, aggressive malignancy with no established standard of care for metastatic disease. The prognosis is dismal; median survival ranges from 12 to 20 months, and long-term survival is exceptional. Case Presentation: We present a 67-year-old man diagnosed in 2018 with metastatic SCCB involving the liver, bone, and ureter. He achieved a complete metabolic response following six cycles of cisplatin–etoposide, followed by consolidative pelvic radiotherapy with a bladder boost. Upon disease progression in 2019, molecular profiling identified a high tumour mutational burden (19.9 mut/Mb), PD-L1 CPS > 1%, and multiple genomic alterations (including MDM2, RAD51D, and TERT). Dual immune checkpoint inhibition (ICI) with ipilimumab and nivolumab was initiated. Although treatment was interrupted and subsequently discontinued due to grade 3 immune-related adverse events, including hepatitis and pneumonitis, the patient maintained a sustained remission off therapy. In January 2025, nearly seven years post-diagnosis, he developed a solitary frontal brain metastasis. He underwent resection and adjuvant stereotactic radiosurgery, achieving local control. He remains under surveillance with no evidence of extracranial recurrence. Conclusions: This case illustrates one of the longest reported survivals in metastatic SCCB. It highlights the utility of molecular profiling in guiding salvage therapy and the potential for durable ICI responses even after discontinuation due to toxicity. Furthermore, late recurrence in the brain emphasizes the central nervous system’s role as a sanctuary site, necessitating prolonged vigilance.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol^®-Modified citrus pectin (P-MCP) is a food supplement categorized as GRAS (Generally Recognized As Safe) by the FDA. It is a competitive inhibitor of the galectin-3 protein, which is involved in cancer pathogenesis. In an early report of the present phase 2 study, P-MCP treatment for 6 months led to prostate-specific antigen doubling time (PSADT) improvement in 75% of patients with BRPC-M0. Herein, we report the second long-term treatment phase of an additional 12 months of P-MCP therapy (4.8 g × 3/day orally) in patients without disease progression after the initial 6 months of therapy. Of the 46 patients that entered the second treatment phase, 7 patients withdrew consent and decided to continue therapy out of pocket, and 39 initiated the second treatment phase. After a total of 18 months of P-MCP treatment, 85% (n = 33) had a durable long-term response, with 62% (n = 24) showing decreased/stable PSA, 90% (n = 35) PSADT improvement, and all with negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long-term durable efficacy and is safe in BRPC-M0.

The optimal therapy for patients with non-metastatic biochemically relapsed prostate cancer (BRPC-M0) after local therapy is elusive. Thus, the evaluation of new non-toxic compounds in BRPC-M0 patients is warranted. PectaSol® modified citrus pectin (P-MCP) is a food supplement generally recognized as safe (GRAS) by the Food and Drug Administration (FDA) and is a competitive inhibitor of galectin-3 protein, involved in cancer pathogenesis. P-MCP treatment of BRPC-M0 patients for 6 months led to a 75% prostate-specific antigen doubling time (PSADT) improvement. To determine the longer-term effects of P-MCP we investigated an additional 12 months of treatment (phase II) with oral P-MCP at 4.8 grams X 3/day in patients with no disease progression in the previous 6 months. Of the 46 patients that entered the second phase, 7 patients withdrew consent and continued therapy independently, and 39 received another 12 months of therapy. After a total of 18 months P-MCP treatment, 62% (n=24) had a decreased/stable PSA, 90% (n=35) had improved PSADT, and 85% (n=33) had a durable long-term response, with a decreased/stable PSA, and/or improvement of PSADT, and negative scans. No patient had grade 3/4 toxicity. In conclusion, P-MCP may have long term durable efficacy, and is safe, in BRPC-M0.

Optimal therapy of biochemically relapsed prostate cancer (BRPC) after local treatment is elusive. An established modified citrus pectin (PectaSol^®, P-MCP), a dietary polysaccharide, is an established antagonist of galectin-3, a carbohydrate-binding protein involved in cancer pathogenesis. Based on PSA dynamics, we report on the safety and the primary outcome analysis of a prospective phase II study of P-MCP in non-metastatic BRPC based. Sixty patients were enrolled, and one patient withdrew after a month. Patients (n = 59) were given P-MCP, 4.8 grams X 3/day, for six months. The primary endpoint was the rate without PSA progression and improved PSA doubling time (PSADT). Secondary endpoints were the rate without radiologic progression and toxicity. Patients that did not progress by PSA and radiologically at six months continued for an additional twelve months. After six months, 78% (n = 46) responded to therapy, with a decreased/stable PSA in 58% (n = 34), or improvement of PSADT in 75% (n = 44), and with negative scans, and entered the second twelve months treatment phase. Median PSADT improved significantly (p = 0.003). Disease progression during the first 6 months was noted in only 22% (n = 13), with PSA progression in 17% (n = 10), and PSA and radiologic progression in 5% (n = 3). No patients developed grade 3 or 4 toxicity.

Cannabis or its derivatives are widely used by patients with cancer to help with cancer symptoms and treatment side effects. However, cannabis has potent immunomodulatory properties. To determine if cannabis consumption during immunotherapy affects therapy outcomes, we conducted a prospective observatory study including 102 (68 immunotherapy and 34 immunotherapy plus cannabis) consecutive patients with advanced cancers who initiated immunotherapy. Cannabis consumption correlated with a significant decrease in time to tumor progression and overall survival. On the other hand, the use of cannabis reduced therapy-related immune-related adverse events. We also tested the possibility that cannabis may affect the immune system or the tumor microenvironment through the alteration of the endocannabinoid system. We analyzed a panel of serum endocannabinoids (eCBs) and eCB-like lipids, measuring their levels before and after immunotherapy in both groups. Levels of serum eCBs and eCB-like lipids, before immunotherapy, showed no significant differences between cannabis users to nonusers. Nevertheless, the levels of four eCB and eCB-like compounds were associated with patients’ overall survival time. Collectively, cannabis consumption has considerable immunomodulatory effects, and its use among cancer patients needs to be carefully considered due to its potential effects on the immune system, especially during treatment with immunotherapy.

Introduction: Up to 50% of adults with congestive heart failure (CHF) and left ventricular dysfunction demonstrate Cheyne–Stokes respiration (CSR), although the mechanisms remain controversial. Because CSR has been minimally studied in children, we sought to assess the prevalence of CSR in children with low and high output cardiac failure. We hypothesized that the existence of CSR only in children with low output CHF would support the importance of circulatory delay as a CSR mechanism. Methods: Thirty patients participated: 10 children with CHF, 10 matched children with no heart disease, and 10 adults with CHF. All participants underwent an in-laboratory polysomnographic sleep study. Results: CHF children's average age (±SEM) was 3.6 ± 2.1 years vs. 3.7 ± 2 years in the age-matched control group. The average ejection fraction of three children with low output CHF was 22 ± 6.8%. The remaining seven had normal-high cardiac output. Compared to control children, CHF children were tachypneic and tachycardic during stable sleep (55.1 ± 6.7 vs. 26.9 ± 3 breath/min and 127.6 ± 8.7 vs. 97.6 ± 6.9 beats/min, respectively, p < 0.05 for both). They had shorter total sleep time (195 ± 49 vs. 373 ± 16 min, p < 0.05) with a low sleep efficiency of 65.6 ± 6%. None of the children had a pattern of CSR at any time during the studies while the adults with CHF had 40% prevalence of CSR. Conclusions: The complete absence of CSR in our sample of children with CHF compared to the 40% prevalence in the adults with CHF we studied, suggests that CSR may be an age-dependent phenomenon. Thus, we speculate that regardless of the exact mechanism which drives CSR, age is an over-riding factor.