Search

BACKGROUND The inclusion of immune checkpoint inhibitors (ICIs) in the treatment of operable stage III non-small-cell lung cancer is becoming a new standard. Programmed death-ligand 1 (PD-L1) protein expression on tumor cells has emerged as the most important biomarker for sensitivity to ICIs targeting the programmed cell death protein 1 (PD-1)-PD-L1 axis. Little is known about the impact of neoadjuvant treatment on PD-L1 expression. PATIENTS AND METHODS We assessed PD-L1 expression by immunohistochemistry (Ventana SP263 assay) on tumor cells in treatment-naive diagnostic tumor samples and matched lung resections from patients with stage III non-small-cell lung cancer included in the Swiss Group for Clinical Cancer Research (SAKK) trials 16/96, 16/00, 16/01, and 16/14. All patients received neoadjuvant chemotherapy (CT) with cisplatin/docetaxel, either as single modality (CT), with sequential radiotherapy [chemoradiation therapy (CRT)] or with the PD-L1 inhibitor durvalumab (CT + ICI). RESULTS Overall, 132 paired tumor samples were analyzed from patients with neoadjuvant CT (n = 69), CRT (n = 33) and CT + ICI (n = 30). For CT and CRT, PD-L1 expression before and after neoadjuvant treatment did not differ significantly (Wilcoxon test, P = 0.94). Likewise, no statistically significant difference was observed between CT and CRT for PD-L1 expression after neoadjuvant treatment (P = 0.97). For CT + ICI, PD-L1 expression before and after neoadjuvant treatment also did not differ significantly (Wilcoxon test, P > 0.99). Event-free survival and overall survival for patients with downregulation or upregulation of PD-L1 expression after neoadjuvant treatment were similar. CONCLUSIONS In our cohort of patients neoadjuvant treatment did not influence PD-L1 expression, irrespective of the specific neoadjuvant treatment protocol. Dynamic change of PD-L1 expression did not correlate with event-free survival or overall survival.

Vinorelbine chemotherapy with granulocyte colony stimulating factor (G CSF) stimulation is a widely applied non myelosuppressive mobilization regimen in Switzerland for myeloma patients but its neurotoxic potential limits its use in patients with bortezomib induced polyneuropathy. In this single center study we alternatively evaluated safety and effectiveness of gemcitabine chemotherapy with G CSF for mobilization of autologous stem cells. Between March 2012 and February 2013 all bortezomib pretreated myeloma patients planned to undergo first line high dose melphalan chemotherapy received a single dose of 1250?mg/m2 gemcitabine with G CSF started on day 4. The 24 patients in this study had received a median of four cycles of bortezomib dexamethason based induction. Bortezomib related polyneuropathy was identified in 21 patients (88) by clinical evaluation and a standardized questionnaire. Administration of gemcitabine mobilization did not induce new or aggravate pre existing neuropathy. Stem cell mobilization was successful in all 24 patients with a single day of apheresis being sufficient in 19 patients (78). The median yield was 9.51×10(6) CD34+ cells/kg. Stem collection could be accomplished at day 8 in 67. Our data suggest that single dose gemcitabine together with G CSF is an effective mobilization regimen in myeloma patients and a safe alternative non myelosuppressive mobilization chemotherapy for myeloma patients with bortezomib induced polyneuropathy.

BACKGROUND: The aim of this multicenter trial was to prospectively evaluate neo-adjuvant chemotherapy followed by extrapleural pneumonectomy (EPP) and radiotherapy, including quality of life as outcome. PATIENTS AND METHODS: Eligible patients had malignant pleural mesothelioma of all histological types, World Health Organization performance status of zero to two and clinical stage T1-T3, N0-2, M0 disease considered completely resectable. Neo-adjuvant chemotherapy consisted of three cycles of cisplatin and gemcitabine followed by EPP. Postoperative radiotherapy was considered for all patients. RESULTS: In all, 58 of 61 patients completed three cycles of neo-adjuvant chemotherapy. Forty-five patients (74%) underwent EPP and in 37 patients (61%) the resection was complete. Postoperative radiotherapy was initiated in 36 patients. The median survival of all patients was 19.8 months [95% confidence interval (CI) 14.6-24.5]. For the 45 patients undergoing EPP, the median survival was 23 months (95% CI 16.6-32.9). Psychological distress showed minor variations over time with distress above the cut-off score indicating no morbidity with 82% (N = 36) at baseline and 76% (N = 26) at 3 months after surgery (P = 0.5). CONCLUSIONS: The observed rate of operability is promising. A median survival of 23 months for patients undergoing EPP compares favourably with the survival reported from single center studies of upfront surgery. This approach was not associated with an increase in psychological distress.

BACKGROUND: The Ca2+-binding protein calretinin (CR), while absent in normal colonocytes, is expressed in the majority of poorly differentiated colon carcinomas, and is hypothesized that mutations in the distal part (from exon 7 to 10) of the CR gene (CALB2) could be responsible for the aberrant CR expression. MATERIALS AND METHODS: Using PCR amplification of genomic DNA and restriction fragment length polymorphism analysis, four single nucleotide polymorphisms (SNPs) were identified in CALB2 intron 9. RESULTS: A significant positive association between the genotype at SNP513 and colon cancer was found: more C/T heterozygotes were found in patients with colon tumors (60%) compared to healthy controls (35%) or patients with lung tumors (38%). Our results indicate that C/T heterozygosity at position 513 is linked to CR expression in colon tumors and colon cancer cell lines, suggesting a link with increased carcinogenesis. CONCLUSION: The SNP513 in human CALB2 may thus be a predictive marker for colon tumors.

Although chemotherapy is considered the cornerstone of treatment for small cell lung cancer (SCLC), the majority of SCLC patients relapse and die of their disease within 2 years of diagnosis. Until newer, more effective drugs are developed, both optimization of available chemotherapeutic regimens and the use of combined chemotherapy/radiotherapy will be required to improve the survival of SCLC patients. Combining ifosfamide, carboplatin, and etoposide, among the most active single agents against SCLC, into the ICE regimen was a logical move that has resulted in improved response and survival rates. In limited and extensive SCLC, respectively, ICE and ICE administered with vincristine (VICE) have achieved overall response rates of 79% to 94% and 77% to 100% and 2-year survival rates of 24% to 33% and 9% to 25%, respectively. Treatment-related toxicities, especially myelosuppression, have hindered efforts to accelerate the administration of ICE and VICE regimens and to incorporate them into combined-modality treatments. However, the use of hematologic support measures, including growth factors and peripheral blood progenitor cells, may pave the way for maximizing the effectiveness of these regimens.