Survival outcomes in patients with gastric and gastroesophageal junction adenocarcinomas treated with perioperative chemotherapy with or without preoperative radiotherapy.

BACKGROUND: Perioperative chemotherapy (POC) is one standard approach for the treatment of resectable cancers of the stomach and gastroesophageal junction (GEJ), whereas there has been growing interest in preoperative therapies. The objective of the current study was to compare survival between patients treated with preoperative chemoradiotherapy and adjuvant chemotherapy (PCRT) with those receiving POC using a large database. METHODS: The National Cancer Data Base was queried for patients diagnosed between 2004 and 2013 with American Joint Committee on Cancer clinical group stage IB to stage IIIC (excluding T2N0 disease) adenocarcinoma of the stomach or GEJ. Patients treated with definitive surgery and POC with or without preoperative radiotherapy of 41 to 54 Gy were included. Overall survival (OS) was defined from the date of definitive surgery and estimated using the Kaplan-Meier method. A total of 14 patient and treatment variables were used for propensity score matching (PSM). RESULTS: A total of 1048 patients were analyzed: 53.2% received POC and 46.8% received PCRT. The primary tumor site was the GEJ in 69.1% of patients and stomach in 30.9% of patients. The median age of the patients was 60 years, and the median follow-up was 25.8 months. The use of PCRT was associated with a greater pathologic complete response rate of 13.1% versus 8.2% (P = .01). POC was associated with a decreased risk of death in unmatched groups (hazard ratio [HR], 0.83; P = .043). Using PSM cohorts, POC decreased the risk of death with a median OS of 45.1 months versus 31.4 months (HR, 0.70; P = .016). The 2-year OS rate was 72.9% versus 62.5% and the 5-year OS rate was 40.7% versus 33.1% for POC versus PCRT, respectively. Survival favored POC in PSM gastric (HR, 0.41; P = .07) and GEJ (HR, 0.77; P = .08) patient subgroups. CONCLUSIONS: The addition of preoperative radiotherapy to POC appears to be associated with an increased risk of death in patients with resectable gastric and GEJ cancers.

Reduced-volume tumor-bed boost is not associated with inferior local control and survival outcomes in high-risk medulloblastoma.

BACKGROUND: Radiotherapy boost to the entire posterior fossa (PF) is standard of care for high-risk (H-R) medulloblastoma patients; the utility of tumor bed (TB)-only boost is unclear. The purpose of this study was to examine the impact of PF versus TB boost volume on tumor control and survival in the H-R medulloblastoma population. METHODS: Single-institution records for patients with H-R medulloblastoma were reviewed. The median craniospinal irradiation dose was 36 Gy (range, 23.4-45 Gy), and boost doses to either PF or TB were 54 to 55.8 Gy. PF (local) failures were scored as in-field, marginal (between 80% and 95% isodose lines), or distant. Kaplan-Meier methods and Cox proportional hazards were used to assess the impact of radiation boost technique on local control (LC) and survival endpoints. RESULTS: Thirty-two patients with H-R medulloblastoma were treated between 1990 and 2015, with a median follow-up length of 5.12 years. Twenty-two patients received PF boost, and 10 received TB boost. Patient and disease characteristic were comparable between groups. A total of 11 PF failures occurred, including 3 isolated LFs (2 in the PF and 1 in the TB group). Most PF failures were in-field: three of four in the TB group and six of seven in the PF group; the remainder were marginal failures. TB boost was not associated with inferior LC (hazard ratio [HR] 0.86, log-rank P = 0.81) or overall survival (HR 1.40, P = 0.56) compared with PF boost. CONCLUSION: Reduced-volume radiotherapy boost to the TB does not appear to compromise LC or survival in patients with H-R medulloblastoma; it may reduce the risk of ototoxicity.

Musculoskeletal outcomes and the effect of radiation to the vertebral bodies on growth trajectories for long-term survivors of high-risk neuroblastoma.

OBJECTIVE: Here, we report musculoskeletal outcomes and the impact of radiotherapy dose on vertebral body growth for an institutional series of long-term survivors of high-risk neuroblastoma. METHODS: We conducted a retrospective study of 23 patients who were disease-free and at least 36 months from the end of treatment. The patients were initially treated from July 2003 to May 2012. Patient records were reviewed for growth percentiles (obtained at approximately 6-month intervals from onset of treatment to the last follow-up) and musculoskeletal comorbidities. RT plans and most recent surveillance CT scans were reviewed for locations of in-field vertebral bodies and corresponding vertebral growth patterns. RESULTS: The median follow-up was 7.93 years. The median prescribed radiation dose was 21.6 Gy. Musculoskeletal abnormalities included scoliosis (5 patients), muscular hypoplasia (3), and hypodontia (1). The median growth percentile at treatment onset was 35.5 (range, 4.7-100) versus 10 (0-94.1) at the last follow-up. The median numbers of vertebral bodies encompassed (by at least half of their volume) by the 5-, 10-, 15-, and 20-Gy isodose lines were 7 (mean, 6.78), 7 (6.56), 6 (6.17), and 6 (5.52), respectively. Sixteen patients (70.0%) had in-field abnormalities in vertebral body growth, manifesting as stretches of successive vertebral bodies at the same height, while normally there is a gradual vertebral body height increase progressing caudally down the spinal column. CONCLUSIONS: Musculoskeletal abnormalities, below average height, and stunted in-field vertebral body growth are routine in long-term survivors of high-risk neuroblastoma. Sparing vertebral bodies when feasible may lead to improvement in patient growth trajectories.

Prognostic relevance of human papillomavirus infection in anal squamous cell carcinoma: analysis of the national cancer data base.

BACKGROUND: To examine the prognostic relevance of human papillomavirus (HPV) infection for anal squamous cell carcinoma (ASCC) patients treated with chemoradiation (CRT) in the National Cancer Data Base (NCDB). METHODS: The 2014 NCDB was queried for non-metastatic, histologically confirmed, ASCC patients diagnosed between 2004 and 2013. Patients were required to have HPV status documented in order to be eligible. Patients were then stratified into two groups: HPV+ and HPV-. Univariate analysis (UVA) was performed using the χ2 test for categorical covariates and ANOVA for numerical covariates. Multivariable analysis (MVA) was performed using Cox proportional hazard model for overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were generated for each covariate. To minimize selection bias, propensity score (PS) weighting was implemented to balance OS related variables between the groups including: age, education level, stage, diagnosis year, insurance type, and agent of chemotherapy. RESULTS: A total of 1,063 patients were eligible. Patients were stratified into HPV+ (n=498, 46.8%) and HPV- (n=565, 53.2%). After PS weighting, MVA for OS showed that for men, HPV infection was associated with better OS (HR: 0.60, 95% CI: 0.38-0.96; P=0.034). However, for women, HPV infection did not significantly influence survival (HR: 1.47, 95% CI: 0.96-2.25; P=0.074). CONCLUSIONS: To our knowledge, this is the largest patient series evaluating the impact of HPV infection on OS in patients with anal cancer. We found that HPV infection is associated with a statistically significant better survival for men with ASCC. In contrast, for women, HPV infection did not significantly influence survival.

Radiotherapy and Male Breast Cancer: A Population-based Registry Analysis.

BACKGROUND: The local-regional management of female breast cancer has been extensively investigated worldwide. The optimal approach for males diagnosed with breast cancer is less clear. We have analyzed the treatment of male breast cancer using a population-based national registry to determine the impact of surgery and radiation therapy on survival. MATERIALS AND METHODS: The Surveillance Epidemiology and End Results (SEER) database was queried to identify males with invasive ductal carcinoma of the breast who underwent primary surgical resection (radical mastectomy, modified radical mastectomy, total mastectomy, or segmental) for the years 1983 to 2002. Demographic, clinical, and pathologic data were culled and analyzed to determine the impact of radiation therapy (RT) following resection. Survival rates were estimated using the Kaplan-Meier method and significance was determined using the log-rank test (P<0.05). Multivariate analysis with the Cox proportional hazards model was performed to determine factors significant for overall (OS) and cause-specific survival (CSS). RESULTS: A total of 1337 patients met the eligibility criteria and were analyzed. Median follow-up was 7.3 years (range, 1 mo to 25 y). Most men underwent modified radical mastectomy (n=1062) with a minority undergoing segmental (n=113). About 329 men received postoperative external beam RT. The median rates of OS and CSS for all men were 10.5 years and not yet reached, respectively. The surgical procedure did not significantly associate with OS or CSS. By stage, RT was associated with improved OS for stage I (P=0.03). There was a trend for improved survival with stage II (P=0.21) and III (P=0.15). RT was not associated with improved CSS by stage. RT improved rates of OS and CSS in N2 patients without reaching statistical significance (P=0.10 and 0.22). On multivariate analysis, advancing age, stage and grade, and no postoperative RT predicted for worse OS. However, when controlled for those with known hormone receptor status (n=978), only the factors of advancing age, stage, grade, and hormone receptor negativity predicted for worse OS. Advancing age, stage, and grade were the only predictors of CSS irrespective of the cohort analyzed. CONCLUSIONS: The primary surgical procedure did not ultimately influence OS or CSS in this population-based registry of males with breast cancer. A statistically nonsignificant improvement with postoperative RT was observed in men with lymph node involvement, larger tumor size, or higher stage. When controlled for age, stage, and grade in multivariate analysis, postoperative RT predicted for improved OS but not CSS. These data suggest a beneficial effect of RT in the postoperative setting. A prospective study is necessary to further elucidate appropriate treatment strategies for men with breast cancer.

Practice patterns of stroke screening and hydroxyurea use in children with sickle cell disease: a survey of health care providers.

Incidence of stroke in sickle cell disease (SCD) has declined with the use of transcranial Doppler ultrasound and chronic transfusion therapy. There is little information regarding their use in genotypes other than HbSS and HbSß. Silent cerebral infarcts (SCIs) have been identified by magnetic resonance imaging (MRI) in SCD patients and it is believed that these may increase the risk of overt stroke. No evidence-based guidelines exist regarding MRI screening for SCIs. Hydroxyurea is a standard therapy in patients with history of acute chest syndrome and severe, recurrent, SCD-associated pain episodes, but has not been established for use with other sickle-associated morbidities. A total of 102 institutions received a survey (with 62 responses) to assess the use of transcranial Doppler ultrasound for stroke screening, use of screening MRI for SCIs, and institutional patterns for prescribing hydroxyurea. Nineteen percent of institutions screen genotypes other than HbSS and HbSß, and 24% use MRI to screen for SCIs. Twenty-six percent of institutions prescribed hydroxyurea in patient found to have SCIs. Results indicate significant variation in stroke screening and hydroxyurea use often correlating with clinic size, number of physician providers, and geographic location. There are currently no evidence-based guidelines to support many of these practices.

Thoracic spinal metastasis of merkel cell carcinoma in an immunocompromised patient: case report.

Study Design Case report. Objective Merkel cell carcinoma (MCC), an uncommon cutaneous neuroendocrine malignancy, is a rare cause of spinal metastasis, with only five cases previously reported. We report a rare case of MCC metastatic to the spine in an immunocompromised patient. Methods A 55-year-old male with previously resected MCC, immunocompromised due to cardiac transplant, presented with sharp mid-thoracic back pain radiating around the trunk to the midline. Computed tomography of the thoracic spine showed a dorsal epidural mass from T6 to T8 with compression of the spinal cord. Laminectomy and subtotal tumor resection were performed, and pathology confirmed Merkel cell tumor through immunohistochemistry staining positive for cytokeratin 20 and negative for thyroid transcription factor-1. Results Further treatment with radiation therapy was initiated, and the patient did well for 4 months after surgery, but returned with a lesion in the cervical spine. He then opted for hospice care. Conclusions With an increasing number of immunocompromised patients presenting with back pain, MCC should be considered in the differential diagnosis of spinal metastatic disease.