Perioperative Chemotherapy in Elderly Patients with Locally Advanced Adenocarcinoma of the Stomach and the Esophagogastric Junction: A Retrospective Cohort Analysis of Toxicity and Efficacy at the National Center for Tumor Diseases, Heidelberg.

OBJECTIVE: Esophagogastric cancer occurs more frequently in older patients, but these are underrepresented in clinical studies establishing the current treatment standards for perioperative chemotherapy in locally advanced disease. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens. METHODS: Using a prospectively generated database, we analyzed 63 patients aged ≥70 years undergoing perioperative chemotherapy for locally advanced esophagogastric cancer. The information included Eastern Cooperative Oncology Group (ECOG) performance status, comorbidity index, body mass index, regimen of chemotherapy, toxicity, dosage adjustments, date of surgery, application of adjuvant treatment, date of progression, and date of death. Survival times were calculated. RESULTS: The median age was 73 years. 96.8% of the patients received an oxaliplatin-containing regimen. In 17.5% of the patients, the dosage was reduced, and treatment was previously permanently stopped in 7.9%; 80% of the patients underwent curatively intended surgery, but only 27.5% of those undergoing resection started adjuvant treatment. Major histological regression was observed in 21.6% of the patients. The median survival was 19.1 months. Significantly improved survival times were observed for patients undergoing surgery (p = 0.008) and for patients with a triplet therapy (p = 0.004). Survival was worse for patients aged ≥75 years. CONCLUSION: perioperative treatment is feasible and effective in elderly patients with esophagogastric cancer.

Palliative chemotherapy for pancreatic adenocarcinoma: a retrospective cohort analysis of efficacy and toxicity of the FOLFIRINOX regimen focusing on the older patient.

BACKGROUND: Pancreatic cancer occurs more frequently in older patients, but these are underrepresented in the phase III clinical studies that established the current treatment standards. This leads to uncertainty regarding the treatment of older patients with potentially toxic but active regimens like FOLFIRINOX. METHODS: We conducted a retrospective analysis of patients treated according to the FOLFIRINOX protocol at our institution between 2010 and 2014 with a focus on older patients. RESULTS: Overall survival in our cohort was 10.2 months. Only 43% of patients did not need dose adaptations, but dose reductions did not lead to an inferior survival. We did not find evidence that patients aged 65 years and older deemed fit enough for palliative treatment had more toxicities or a worse outcome than younger patients. CONCLUSION: We conclude that treatment with the FOLFIRINOX protocol in patients with pancreatic cancer should not be withhold from patients solely based on their chronological age but rather be based on the patient's performance status and comorbidities.

Hepatitis B virus infection is associated with deletion of chromosome 8p in multiple myeloma.

Serological analyses within epidemiological cohort and case-control studies indicate to an association between HBV infection and risk of multiple myeloma (MM). To verify the relationship with an independent approach, we investigated the correlation between HBV positivity and chromosomal aberrations within 680 patients of the National Center for Tumor Diseases Heidelberg for which the serological HBV status (HBsAg and anti-HBc) and FISH data for five gains (1q21, 9q34, 11q23, 15q22, 19q13), five losses (6q21, 8p21, 13q14, 17p13, 22q11), and three IgH translocations [t(4,14), t(11,14), t(14,16)] were available. Deletion of 8p21 and 13q14 were shown associated with HBV positivity within hepatocellular carcinoma in other investigations. In the present evaluation, the odds ratio for loss of 8p21 was significantly elevated (OR = 2.74, 95% CL = 1.36-5.50, P = 0.0048) and for loss of 13q14 non-significantly increased (OR = 1.40, 95% CL = 0.74-2.65) in anti-HBc positive patients. The results provide further support for a role of HBV infection in the pathogenesis of MM.

Human papillomavirus as prognostic marker with rising prevalence in neck squamous cell carcinoma of unknown primary: A retrospective multicentre study.

Patients with neck squamous cell carcinomas of unknown primary tumour (NSCCUP) present with lymph node metastasis without evidence for a primary tumour. Most patients undergo an aggressive multimodal treatment, which induces severe, potentially unnecessary toxicity. Primary tumours of NSCCUP can be hidden in the oropharynx. Human papillomavirus (HPV) is causally involved in a subgroup of oropharyngeal squamous cell carcinomas (OPSCC) associated with early lymph node metastasis and good prognosis. Detection of markers for HPV transformation in NSCCUP could allow focussing on the oropharynx in primary tumour search and could be of value for choice and extent of treatment. In a retrospective multicentre study (Germany, Italy and Spain), we analysed metastatic lymph nodes from 180 NSCCUP patients for the presence of HPV DNA, HPV E6*I mRNA and cellular p16INK4a overexpression, a surrogate marker for HPV-induced transformation. HPV status, defined as positivity for viral mRNA with at least one additional marker, was correlated with clinical parameters and survival outcome. A substantial proportion (16%) of NSCCUP were HPV-driven, mainly by HPV16 (89%). HPV prevalence increased with year of diagnosis from 9% during 1998-2004 to 23% during 2005-2014 (p = 0.007). HPV-driven NSCCUP had significantly better overall and progression-free survival rates (p ≤ 0.008). Based on this survival benefit, it is contended that HPV RNA status should be included in NSCCUP diagnosis and in therapeutic decision-making. Deintensification of radiation in patients with HPV-driven NSCCUP, while concurrently concentrating on the oropharynx appears to be a promising therapeutic strategy, the efficacy of which should be assessed in prospective trials. To our knowledge, this is the largest study on HPV in NSCCUP.