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Patients with retinoblastoma and chromosome 13q deletions have increased chemotherapy-related toxicities.

ABSTRACT: A total of 5-10% of patients with retinoblastoma (RB) harbor deletion of the long arm (q) chromosome 13 (13q-). The treatment-related toxicities in this population have not been described.Sixty-eight RB patients on a single institutional protocol (RET5) from 2005 to 2010 were reviewed. Genetic screening identified 11 patients (seven female) with 13q-. Patients with early (Reese-Ellsworth [R-E] group I-III) disease (6/23 with 13q-) received eight courses of vincristine/carboplatin (VC). Patients with advanced (R-E group IV-V) bilateral disease (2/27 with 13q-) received two courses of vincristine/topotecan (VT) followed by nine courses of alternating VT/VC. Patients undergoing upfront enucleation received histopathology-based chemotherapy: intermediate risk (2/8 with 13q-) or high risk (1/10 with 13q-). Dose reductions were mandated for >7 day delay in two consecutive courses following hematologic toxicity. Grades 3 and 4 hematologic, infectious, and gastrointestinal toxicities were compared between RET5 patients with and without 13q-.Demographics were similar between groups. When present, prolonged neutropenia (median 7 days, range 0-14 days) delayed chemotherapy and resulted in more frequent dose reductions among 13q- patients (5/11) than non-13q- patients (4/57) (P < 0.01). GI toxicity was similar between groups (5/11 13q- vs. 13/57 non-13q-; P = 0.14), but halted chemotherapy in one 13q- patient. Infectious complications and disease outcomes were similar between groups. At follow-up, all patients are alive (median 6.1 years, range 7.6 months-9.5 years).13q- RB patients had a higher incidence of neutropenia requiring chemotherapy dose reductions, but did not have increased treatment failure.

SUBMITTER: Brennan RC

PROVIDER: S-EPMC5683082 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Patients with retinoblastoma and chromosome 13q deletions have increased chemotherapy-related toxicities.

Brennan Rachel C RC Qaddoumi Ibrahim I Billups Catherine A CA Kaluzny Tracy T Furman Wayne L WL Wilson Matthew W MW

Pediatric blood & cancer 20160713 11

<h4>Background</h4>A total of 5-10% of patients with retinoblastoma (RB) harbor deletion of the long arm (q) chromosome 13 (13q-). The treatment-related toxicities in this population have not been described.<h4>Methods</h4>Sixty-eight RB patients on a single institutional protocol (RET5) from 2005 to 2010 were reviewed. Genetic screening identified 11 patients (seven female) with 13q-. Patients with early (Reese-Ellsworth [R-E] group I-III) disease (6/23 with 13q-) received eight courses of vinc ...[more]

PMID: 27409525

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Project description:BACKGROUND:The relationship between chemotherapy-related toxicities and prognosis is unclear. Previous studies have examined the association of myelosuppression parameters or neuropathy with survival and reported conflicting results. This study aims to investigate 13 common chemotherapy toxicities and their association with relapse-free survival and breast cancer-specific survival. METHODS:Chemotherapy-related toxicities were collected prospectively for 6,248 women with early-stage breast cancer from four randomised controlled trials (NEAT; BR9601; tAnGo; Neo-tAnGo). Cox proportional-hazards modelling was used to analyse the association between chemotherapy-related toxicities and both breast cancer-specific survival and relapse-free survival. Models included important prognostic factors and stratified by variables violating the proportional hazards assumption. RESULTS:Multivariable analysis identified severe neutropenia (grades ?3) as an independent predictor of relapse-free survival (hazard ratio (HR)?=?0.86; 95% confidence interval (CI), 0.76-0.97; P?=?0.02). A similar trend was seen for breast cancer-specific survival (HR?=?0.87; 95% CI, 0.75-1.01; P?=?0.06). Normal/low BMI patients experienced more severe neutropenia (P?=?0.008) than patients with higher BMI. Patients with fatigue (grades ?3) showed a trend towards reduced survival (breast cancer-specific survival: HR?=?1.17; 95% CI, 0.99-1.37; P?=?0.06). In the NEAT/BR9601 sub-group analysis by treatment component, this effect was statistically significant (HR?=?1.61; 95% CI, 1.13-2.30; P?=?0.009). CONCLUSIONS:This large study shows a significant association between chemotherapy-induced neutropenia and increased survival. It also identifies a strong relationship between low/normal BMI and increased incidence of severe neutropenia. It provides evidence to support the development of neutropenia-adapted clinical trials to investigate optimal dose calculation and its impact on clinical outcome. This is important in populations where obesity may lead to sub-optimal chemotherapy doses.

Project description:BACKGROUND:Abundant evidences have shown that newly developed chemotherapy regimens improved 5-year survival rate of colorectal cancer (CRC) patients over the past two decades. However, their impact on risk of death from leading causes among elderly patients is still poorly understood. PATIENTS AND METHODS:A retrospective cohort study of 69 718 elderly CRC patients with their first primary tumors in 1992-2009, identified from the 12 areas of Surveillance, Epidemiology, and End Results-Medicare linked database with their Medicare claims up to 2010. Multivariate Cox regression models were used to assess the effect of newly developed chemotherapy regimens, comorbidities, and chemotherapy related toxicities on cause-specific death and their temporal patterns among elderly CRC patients. RESULTS:The leading causes of death among CRC patients were CRC, circulation disorders, and secondary cancers, which accounted for 51.4%, 25%, and 4.6% of all-cause death, respectively. Patients diagnosed in more recent diagnostic time periods were significantly less likely to die of CRC [period 2: 5-year hazard ratio = 0.94, 95% confidence interval (CI) 0.90-0.97; period 3: 0.86, 0.83-0.90], circulation disorders (period 2: 0.94, 0.88-1.00; period 3: 0.80, 0.75-0.87), and more likely to die of secondary cancer (period 3: 1.42, 1.20-1.68) compared with those diagnosed in period 1. Charlson comorbidities index and the selected pre-existing comorbidities were significantly associated with increased 5-year risk of death from all three leading causes. Both hematological and gastric toxicity were associated with reduced risk of death from CRC and circulation disorders. The association between diagnostic time period and risk reduction in death from CRC depended on chemotherapy treatment (P < 0.0001). Subgroup analyses showed that the chemotherapy-dependent significant risk reduction was seen in patients with stage II-III CRC, patients without comorbidities, and patients without toxicities (P < 0.0001 for all). CONCLUSION:The newly developed chemotherapy regimens were associated with the decreased risk of mortality from CRC.

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Patients with retinoblastoma and chromosome 13q deletions have increased chemotherapy-related toxicities.

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Patients with retinoblastoma and chromosome 13q deletions have increased chemotherapy-related toxicities.

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