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Background: This study aimed to evaluate if combining low muscle mass with additional body composition abnormalities, such as myosteatosis or adiposity, could improve survival prediction accuracy in a large cohort of gastrointestinal and genitourinary malignancies., Methods: In total, 2015 patients with surgically-treated gastrointestinal or genitourinary cancer were retrospectively analyzed. Skeletal muscle index, skeletal muscle radiodensity, and visceral/subcutaneous adipose tissue index were determined. The primary outcome was overall survival determined by hospital records. Multivariate Cox hazard models were used to identify independent predictors for poor survival. C-statistics were assessed to quantify the prognostic capability of the models with or without incorporating body composition parameters., Results: Survival curves were significantly demarcated by all 4 measures. Skeletal muscle radiodensity was associated with non-cancer-related deaths but not with cancer-specific survival. The survival outcome of patients with low skeletal muscle index was poor (5-year OS; 65.2%), especially when present in combination with low skeletal muscle radiodensity (5-year overall survival; 50.2%). All examined body composition parameters were independent predictors of lower overall survival. The model for predicting overall survival without incorporating body composition parameters had a c-index of 0.68 but increased to 0.71 with the inclusion of low skeletal muscle index and 0.72 when incorporating both low skeletal muscle index and low skeletal muscle radiodensity/visceral adipose tissue index/subcutaneous adipose tissue index., Conclusion: Patients exhibiting both low skeletal muscle index and other body composition abnormalities, particularly low skeletal muscle radiodensity, had poorer overall survival. Models incorporating multiple body composition prove valuable for mortality prediction in oncology settings., (© 2024 The Author(s). Journal of Parenteral and Enteral Nutrition published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Background: In this multicenter, single-arm, multicohort, phase 2 trial, the efficacy of nivolumab and ipilimumab was evaluated in patients with advanced rare genitourinary cancers, including bladder and upper tract carcinoma of variant histology (BUTCVH), adrenal tumors, platinum-refractory germ cell tumors, penile carcinoma, and prostate cancer of variant histology (NCT03333616)., Methods: Patients with rare genitourinary malignancies and no prior immune checkpoint inhibitor exposure were enrolled. Patients received nivolumab at 3 mg/kg and ipilimumab at 1 mg/kg intravenously every 3 weeks for 4 doses, and this was followed by 480 mg of nivolumab intravenously every 4 weeks. The primary endpoint was the objective response rate (ORR) by the Response Evaluation Criteria in Solid Tumors (version 1.1)., Results: Fifty-five patients were enrolled at 6 institutions between April 2018 and July 2019 in 3 cohorts: BUTCVH (n = 19), adrenal tumors (n = 18), and other tumors (n = 18). The median follow-up was 9.9 months (range, 1 to 21 months). Twenty-eight patients (51%) received 4 doses of nivolumab and ipilimumab; 25 patients received nivolumab maintenance for a median of 4 cycles (range, 1-18 cycles). The ORR for the entire study was 16% (80% confidence interval, 10%-25%); the ORR in the BUTCVH cohort, including 2 complete responses, was 37%, and it was 6% in the other 2 cohorts. Twenty-two patients (40%) developed treatment-related grade 3 or higher toxicities; 24% (n = 13) required high-dose steroids (≥40 mg of prednisone or the equivalent). Grade 5 events occurred in 3 patients; 1 death was treatment related., Conclusions: Nivolumab and ipilimumab resulted in objective responses in a subset of patients with rare genitourinary malignancies, especially those with BUTCVH. An additional cohort exploring their activity in genitourinary tumors with neuroendocrine differentiation is ongoing., Lay Summary: Patients with rare cancers are often excluded from studies and have limited treatment options. Fifty-five patients with rare tumors of the genitourinary system were enrolled from multiple sites and were treated with nivolumab and ipilimumab, a regimen used for kidney cancer. The regimen showed activity in some patients, particularly those with bladder or upper tract cancers of unusual or variant histology; 37% of those patients responded to therapy. Additional studies are ongoing to better determine who benefits the most from this combination., (© 2020 American Cancer Society.)

Background: Pediatric paired box 3:forkhead box protein O1 fusion-negative (PF-) rhabdomyosarcoma (RMS) represents a diverse spectrum of tumors with marked differences in histology, myogenic differentiation, and clinical behavior., Methods: This study sought to evaluate the clinical and mutational spectrum of 24 pediatric PF- human RMS tumors with high levels of myogenic differentiation. Tumors were sequenced with OncoPanel v.2, a panel consisting of the coding regions of 504 genes previously linked to human cancer., Results: Most of the tumors (19 of 24) arose at head/neck or genitourinary sites, and the overall survival rate was 100% with a median follow-up time of 4.6 years (range, 1.4-8.6 years). RAS pathway gene mutations were the most common mutations in PF-, highly differentiated RMS tumors. In addition, Hedgehog (Hh) and mechanistic target of rapamycin (mTOR) gene mutations with evidence for functional relevance (high-impact) were identified in subsets of tumors. The presence of Hh and mTOR pathway gene mutations was mutually exclusive and was associated with high-impact RAS pathway gene mutations in 3 of 4 Hh-mutated tumors and in 1 of 6 mTOR-mutated tumors., Conclusions: Interestingly, Hh and mTOR gene mutations were previously associated with rhabdomyomas, which are also known to preferentially arise at head/neck and genitourinary sites. Findings from this study further support the idea that PF-, highly differentiated RMS tumors and rhabdomyomas may represent a continuous spectrum of tumors. Cancer 2018;124:1973-81. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Cancer deaths among white, foreign-born residents of New York State (exclusive of New York City) during the years 1969 through 1971 were analyzed according to country of birth. The largest numbers of immigrants came from Great Britain, Ireland, Germany, Austria, Poland, Italy, USSR, and Canada. Several distinctive features emerged from these data: Irish immigrants have an increased risk of dying from oropharyngeal, gastrointestinal, lung, and prostate cancers. Among all migrant groups studied, contrasting mortality patterns observed for carcinomas of the stomach, colon, and rectum provide further support for the concept that these neoplasms result from different etiologic processes. For the leukemias, lymphomas, and carcinomas of the breast and colon, each of the migrant groups acquired the higher risk common to others in the host country. This rise in risk suggests a major environmental component for cancers of these sites.

Although rhabdomyosarcoma of the genitourinary tract occurs infrequently in children, it presents a challenging problem to the surgeon, radiotherapist, and oncologist. Thirty-six children with genitourinary rhabdomyosarcoma were treated at our institutions from 1957 to 1985. The primary site of tumor involved the bladder, prostate, or both in 15 patients, the paratesticular structures in 12, and female reproductive organs in nine. Although treatment modalities and philosophies of care varied over the past 27 years, the majority of patients were treated with a combination of surgery, chemotherapy, and radiation therapy. The event-free survival for all patients is 74%. Patients with paratesticular tumors had the best prognosis (88% event-free survival). Regional nodal radiation therapy is not necessary in this favorable group if the retroperitoneal lymph node dissection is negative. Of 15 children with bladder/prostate tumors nine had initial conservative surgery. Of these nine six are long-term survivors, but only three patients have intact bladders. The girls with tumors of the reproductive organs had an event-free survival of 63%; all patients in this group had hysterectomies. Chemotherapy and radiotherapy have not substituted for radical surgical procedures in most children with bladder or prostate rhabdomyosarcomas. Innovative therapeutic approaches are necessary for this group of patients.

Thirty-nine previously untreated children with rhabdomyosarcoma were managed by a coordinated program of surgery, radiation therapy, and chemotherapy during the years 1960 to 1973. The primary tumor was located in the head and neck (24), chest wall (1), abdomen (1), pelvis (10), and lower extremity (3). Radiation therapy consisted of tumor doses of 5000 to 6000 rads delivered in five to six weeks. Combination chemotherapy with actinomyctin-D, vincristine and cyclophosphamide was used after 1968. Seventeen of 25 cases (68%) treated after 1968 are alive two to five years following treatment. Only four of 14 cases (29%) who received less radical therapy before 1968 are alive. A relatively high incidence of local failure (23%) was noted in spite of adequate doses of radiotherapy. None of the four cases with metastatic disease at the time of diagnosis survived. Major complications were mainly noted in patients with orbital rhabdomyosarcoma. Correlation of absolute survival with dose of irradiation, primary site, extent of disease and histologic subtypes of the tumor are discussed.

Delayed hypersensitivity, as determined by skin reactivity to 2-4 dinitrochlorobenzene (DNCB), was tested in 112 patients prior to their undergoing curative radiotherapy. Of the strong DNCB reactors, 84% had an excellent radiation tumor response, while only 48% of the negative reactors had an equivalent response. Almost twice as many strong DNCB reactors were alive and free of disease (NED) at 6 months (70% vs. 38% for nonreactors). Similarly, the positive DNCB reactors had a median survival of 18 months, compared to 10 months for the nonreactors.

Italian death certification data from 1955 to 1979 for total cancer mortality and 30 cancer sites in the population aged 25 to 74, were analyzed using a log-linear Poisson model to isolate the effects of birth cohort, calendar period of death, and age. The most frequent cohort pattern was characterized by increases up to the generations born between 1920 and 1930, followed by stabilization or a slight decrease. This pattern was evident for total cancer mortality in men, and for several common sites, including larynx, lung, esophagus, bladder, female breast, and ovary. Only four sites (pancreas, pleura, intestines in both sexes, and kidney in men) showed cohort values still rising in more recent generations. Stable cohort and period of death curves were observed for cancers of the prostate and testis, whereas trends were steadily going down for neoplasms of the stomach, and (cervix) uteri. Finally, there were a few discontinuous trends (e.g., in the case of brain neoplasms, leukemias, and lymphomas), which probably reflect different effects of improvements in diagnosis and/or treatment. Period of death values increased for lung and other tobacco related sites (chiefly in males) and, up to the early 1970s, for a few other common sites, including intestines, and the female breast. Downward trends over the calendar period were evident for cancers of the stomach and of the (cervix) uteri. Therefore, total cancer mortality trends over the calendar period of death were moderately increasing for men, and slightly decreasing for women.