Defining the optimal segmentation method for measuring somatostatin receptor expressing tumor volume on 68Ga-DOTATATE positron emission tomography/computed tomography to predict prognosis in patients with gastroenteropancreatic neuroendocrine tumors.

OBJECTIVE: We aimed to compare different segmentation methods used to calculate prognostically valuable volumetric parameters, somatostatin receptor expressing tumor volume (SRETV), and total lesion somatostatin receptor expression (TLSRE), measured by 68Ga-DOTATATE PET/CT and to find the optimal segmentation method to predict prognosis. PATIENTS AND METHODS: Images of 34 patients diagnosed with gastroenteropancreatic neuroendocrine tumor (GEPNET) who underwent 68Ga-DOTATATE PET/CT imaging were reanalyzed. Four different threshold-based methods (fixed relative threshold method, normal liver background threshold method, fixed absolute standardized uptake value (SUV) threshold method, and adaptive threshold method) were used to calculate SRETV and TLSRE values. SRETV of all lesions of a patient was summarized as whole body SRETV (WB-SRETV) and TLSRE of all lesions of a patient was computed as whole body TLSRE (WB-TLSRE). RESULTS: WB-SRETVs calculated with all segmentation methods were statistically significantly associated with progression-free survival except WB-SRETVat which was calculated using adaptive threshold method. The fixed relative threshold methods calculated by using 45% (WB-SRETV45%) and 60% (WB-SRETV60%) of the SUV value as threshold respectively, were found to have statistically significant highest prognostic value (C-index = 0.704, CI = 0.622-0.786, P = 0.007). Among WB-TLSRE parameters, WB-TLSRE35%, WB-TLSRE40%, and WB-TLSRE50% had the highest prognostic value (C-index = 0.689, CI = 0.604-0.774, P = 0.008). CONCLUSION: The fixed relative threshold method was found to be the most effective and easily applicable method to measure SRETV on pretreatment 68Ga-DOTATATE PET/CT to predict prognosis in GEPNET patients. WB-SRETV45% (cutoff value of 11.8 cm3) and WB-SRETV60% (cutoff value of 6.3 cm3) were found to be the strongest predictors of prognosis in GEPNET patients.

Prediction of nipple involvement in breast cancer after neoadjuvant chemotherapy: Should we rely on breast MRI to preserve the nipple?

BACKGROUND: Indications for nipple sparing mastectomy (NSM) is extending to post-neoadjuvant chemotherapy (NAC) setting. Eligibility for NSM with an optimum tumor-nipple distance (TND) after NAC is unclear. We examined predictive factors for nipple tumor involvement in patients undergoing total mastectomy following NAC. METHODS: Clinical and pathological data from prospectively collected medical records of women with invasive breast carcinoma, who were undergone NAC and total mastectomy with sentinel lymph node biopsy and/or axillary lymph node dissection were analyzed. PreNAC and postNAC magnetic resonance imaging (MRI) views were examined and a cut-off TND value for predicting the negative nipple tumor status was determined. RESULTS: Among 180 women, the final mastectomy specimen analysis revealed that 12 (7%) had nipple involvement as invasive carcinoma. Patients with nipple involvement had more postNAC multifocal/multicentric tumors (p: 0.03), larger tumors on preNAC and postNAC images (p: 0.002 and p < 0.001), shorter median TNDs on preNAC and postNAC images (7 mm-IQR 1.5-14, p: 0.005 and 8.5 mm-IQR 3-15.5, p < 0.001, respectively), more nipple retraction on preNAC and postNAC images (p: 0.007 and p: 0.006) and more nipple areola complex skin thickening (> 2mm) on preNAC and postNAC images (p < 0.001 and p: 0.01). The best likelihood ratios (LR) belonged to the postNAC positivity of the < 20 mm TND, with a + LR of 3.40, and - LR of 0.11 for nipple involvement. PreNAC positivity of the < 20 mm TND also had a similar - LR of 0.14. CONCLUSION: A TND-cut-off  ≥ 2 cm on preNAC and postNAC MRI was shown to be highly predictive of negative nipple tumor involvement.

Preexisting evidence and outcome of phase III trials in gastrointestinal oncology: a systematic review.

BACKGROUND: A minority of phase III trials in gastrointestinal oncology are positive. We assessed the association between their outcome and the level and characteristics of preexisting evidence. METHODS: EMBASE, PubMed, and proceedings from international meetings were searched for phase III gastrointestinal cancer trials (gastroesophageal, hepatocellular, biliary tract, pancreatic, small bowel, colorectal, anal, stromal, and neuroendocrine) between January 2000 and June 2020. Trials investigating anticancer drugs for advanced disease, with superiority design and standard treatments as control were eligible. The highest level of preexisting evidence was retrieved from the main study report. RESULTS: A total of 193 phase III trials were included, and 69 (35.8%) met their primary endpoint. Positivity rates were as follows: gastroesophageal 37%, colorectal 48%, pancreatic 17.1%, hepatocellular 20%, neuroendocrine 75%, and both biliary tract and GIST 60%. No information about preexisting evidence was found for 44 trials (22.8%). For the remaining 149, preexisting evidence consisted of phase II studies in 123 cases (82.6%) and phase I studies in 26 cases (17.4%). The probability of success was 34.1%, 35.8%, and 35.7%, respectively (P = .934). No parameter from prior studies predicted the outcome of phase III trials except ß < .2 (P = .048). A numerically increased success rate was observed for phase III trials preceded by positive phase II studies (41.9% vs 18.5%, P = .2). CONCLUSIONS: There does not appear to be an association between level of prior evidence and success of phase III gastrointestinal cancer trials. These data, along with the high phase III failure rate, highlight the need to improve the drug development process in this setting.

Regorafenib in combination with immune checkpoint inhibitors for mismatch repair proficient (pMMR)/microsatellite stable (MSS) colorectal cancer.

Immune checkpoint inhibitors (ICIs) have marked a new era of cancer treatment, showing remarkable efficacy in a wide range of solid malignancies. In colorectal cancer (CRC), however, the therapeutic potential of ICIs is limited to the small group (≈5%) of patients with mismatch repair deficient (dMMR)/high microsatellite instable (MSI-H) tumours, which are characterised by high mutational/neo-antigen burden, and an inflammatory tumour microenvironment with abundant tumour-infiltrating lymphocytes. Over the last few years, research has focused on immuno-modulatory strategies that could overcome the inherent resistance to ICIs that is observed in the vast group (≈95%) of patients with mismatch repair proficient (pMMR)/microsatellite stable (MSS) tumours. Among these, the combination of ICIs with multi-kinase inhibitors has gained traction in preclinical studies and clinical trials. Thanks to their multiple targets and mechanisms of action, generally involving key cancer pathways such as oncogenesis, angiogenesis, metastasis, and tumour immunity, these agents can exert synergistic effects with ICIs, eventually turning inherently cold cancers into hot tumours, that can be efficiently recognised and targeted by an activated immune system. Regorafenib is routinely used for chemorefractory CRC with limited efficacy. Preliminary evidence, however, suggests that this multi-kinase inhibitor could be an optimal combination partner for ICIs. In this review article, we explain the biological rationale underlying the synergism between regorafenib and ICIs, discuss the available clinical data in CRC, and take a glance into future perspectives by presenting ongoing trials and possible research developments in this setting.

Real-world assessment of quality-of-life in patients with breast cancer treated with adjuvant endocrine therapy.

Objective: The aim of this study was to investigate quality-of-life (QoL) in breast cancer (BC) patients treated with adjuvant endocrine therapy (AET). Methods: We designed a cross-sectional study of 233 BC patients treated with AET and used the Functional Assessment of Cancer Therapy - Breast questionnaire. Results: No significant difference was observed between endocrine agents. Duration of AET did not affect QoL. In the entire cohort, multivariate analysis determined age (p = 0.034) and switching treatment from tamoxifen to aromatase inhibitors (p = 0.049) as significant positive coefficients of QoL, while comorbidity (p = 0.072) tended to be associated with lower scores. Education level (p = 0.001) and chemotherapy (p = 0.04) were significant predictors of QoL in the tamoxifen group, while comorbidity (p = 0.04), surgery type (p = 0.02), radiotherapy (p = 0.006) and stage (p = 0.009) had a significant impact on QoL in aromatase inhibitors group. Conclusion: Evaluating the well-being of BC patients by QoL questionnaires is of great importance to identify particular subgroups that may require supportive care.

Breast cancer (BC) remains the most common cancer among women worldwide. Hormone receptor-positive (estrogen receptor- and/or progesterone receptor-positive) BC represents 70% of all cases. Advances in the treatment of disease lead to improved patient survival. As a result, quality-of-life (QoL) becomes a major concern in clinical practice. This study aimed to assess the impact of socio-demographic, clinical and treatment-related factors on QoL among patients with BC treated with adjuvant endocrine therapy. We used the Functional Assessment of Cancer Therapy ­ Breast questionnaire to evaluate QoL. In the entire cohort, multivariate analysis determined age and switching treatment from tamoxifen to aromatase inhibitors to be significant positive coefficients of QoL, while comorbidity tended to be associated with lower scores. Education level and chemotherapy were significant determinants of QoL in the tamoxifen group, while comorbidity, surgery type, radiotherapy and disease stage had a significant impact on QoL in the aromatase inhibitor group. These findings can be utilized to identify certain subgroups that may need greater supportive care.

Effect of Adjuvant Chemotherapy in Stage III Cervical Cancer Patients Treated with Concurrent Chemoradiation: A Multicenter Study.

INTRODUCTION: A significant proportion of cervical cancer (CC) patients are diagnosed at a locally advanced stage. Concurrent chemoradiotherapy (CCRT) is the cornerstone of treatment for patients with locally advanced CC. However, the role of adjuvant chemotherapy (AC) after CCRT is controversial. In this study, we analyzed the efficacy of AC after CCRT in stage III CC patients. METHODS: We performed a multicenter, retrospective analysis of 139 International Federation of Gynecology and Obstetrics stage III CC patients treated with CCRT of whom 45.3% received AC. Our goal was to determine the impact of AC on survival in these patients. RESULTS: Five-year progression-free survival (PFS) was 37.5% and 16% in patients receiving CCRT with and without AC, respectively (p = 0.008). Median PFS was 30.9 months (CI 95% 14.8-46.9) and 16.6 months (CI 95% 9.3-23.9) in patients receiving CCRT with and without AC, respectively. Five-year overall survival (OS) was 78.2% and 28.4% in patients receiving CCRT with and without AC, respectively (p < 0.001). Median OS was 132.2 months (CI 95, %66.5-197.8) and 34.9 months (CI 95% 23.1-46.7) in patients receiving CCRT with and without AC, respectively. CONCLUSION: Our study suggests that AC provides OS and PFS benefit in stage III CC patients. Larger studies are needed to identify subgroups of patients who would benefit from AC.

Prognostic Value of Tissue-Resident Memory T Cells and Tumor Microenvironmental Features in Resected Pancreatic Adenocarcinoma

Background: Pancreatic ductal adenocarcinoma differs from other solid tumors with its unique immunosuppressive microenvironment and non-immunogenic feature. There are not many studies in the literature investigating the effect of these features on prognosis. Aims: To investigate the prognostic value of tissue-resident memory T cells, tumor microenvironment features, and tumor-associated immune cells in resected pancreatic ductal adenocarcinomas. Study Design: Retrospective cross-sectional study. Methods: Of 138 patients diagnosed with pancreatic ductal adenocarcinoma between 2011 and 2018, 81 were included in the study. Specimens from operated patients were reassessed separately as peritumoral and intratumoral areas for tissue resident memory cells and tumor microenvironmental elements (tumor infiltrating lymphocytes, tumor stroma, CD204+ macrophages, PDL1+ immune cells). Disease-free survival and overall survival were defined from the date of operation to the date of recurrence and the date of first diagnosis to the date of death, respectively. If the patient was alive, the last visit date was taken into account. Results: The median age at diagnosis was 63 (range: 40-78). The median follow-up period was 18.9 months (range: 1.4-80.4 months). Median overall survival was 23.7 months (1.4-80.4 months) and median disease-free survival was 10.8 months (1.4-74.4 months). Patients with higher intra-tumoral tissue-resident memory cell counts had a longer survival trend than those having lower values (25.6 months vs. 18 months, respectively, P = .84). According to microenvironmental evaluations, lower stromal score (defined as stroma having less desmoplasia and rich in cells) and presence of peritumoral Crohn's-like inflammatory response were associated with higher survival (29.2 months vs. 19.7 months for low vs. high stromal scores, respectively, P = .16 and 30.2 months vs. 18.1 months for the presence of Crohn's-like inflammatory response P = .13). Decreased survival was observed in tumors with increased CD204+ tumor-associated macrophages which were immunosuppressive elements of the microenvironment (12 months vs. 26.3 months for intra-tumoral assessment, P = .29). Conclusion: Tissue-resident memory T cells and other microenvironmental features may be prognostic in resectable pancreatic ductal adenocarcinomas. Further studies with larger cohorts are needed for validation.

Assessment of Prognostic Factors and Adjuvant Treatment Modalities in Adult Head and Neck Soft Tissue Sarcoma Patients Treated With Upfront Surgery.

Objectives Head and neck soft tissue sarcomas (HNSTSs) are a heterogeneous group of rare tumors. Surgical resection with negative margins remains the standard primary treatment for patients with HNSTS. The role of chemotherapy (CT) and radiotherapy (RT) remains controversial. In this multicenter study, we aimed to demonstrate the real-world assessing prognostic factors and the effect of adjuvant treatment modalities in adult patients with HNSTS treated with upfront surgery. Methods We included a total of 47 patients who underwent curative-intent resection of a primary HNSTS between 2000 and 2019. Results The median follow-up was 29 months. The median age of patients was 51 years, and 66% of patients were male. The median relapse-free survival (RFS) of the study population was 31 months (range: 1.0-61.1 months), and the median overall survival (OS) was 115 months (range: 60.8-169.2 months). The univariable analysis revealed that treatment modalities showed a significant impact on RFS (p = 0.021); however, no difference was found in its impact on OS (p = 0.137). R0 resection did not showed impact on RFS (p = 0.130), but a significant association was found with OS (p = 0.004). In multivariable analysis, T stage of the tumor (hazard ratio [HR]: 3.834; 95% CI: 1.631-9.008; p = 0.002) and treatment with surgery and sequential RT and CT (HR: 0.115; 95% CI: 0.035-0.371; p < 0.001) were independent factors associated with RFS. R0 resection was independently associated with OS (HR: 4.902; 95% CI: 1.301-18.465; p = 0.019). Conclusion Our study revealed that R0 resection improved OS, and T3-4 stage of tumor was a negative independent factor for RFS in surgically resected HNSTS patients. The use of sequential CT and RT after resection was associated with a better RFS, which emphasizes the importance of multidisciplinary evaluation of the treatment of HNSTS. Randomized prospective studies are needed.

Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?

PURPOSE: Neoadjuvant chemotherapy is the standard front-line treatment modality in locally advanced breast cancer. Achieving pathological complete response (pCR) is a significant prognostic factor for prolonged disease-free and overall survival. Insulin resistance is defined as a pathological condition in which insulin effect is impaired in peripheral target tissues such as the skeletal muscle, liver, and adipose tissue. The relationship between breast cancer and insulin resistance is controversial. In this study, our aim is to evaluate the role of insulin resistance, body mass index (BMI), metabolic syndrome, and inflammation markers to predict complete response in breast cancer patients who underwent neoadjuvant treatment. METHODS: Data from 55 locally advanced non-diabetic breast cancer patients, treated with neoadjuvant chemotherapy between 2015 and 2017, were retrospectively evaluated. Homeostatic model assessment, IR = insulin resistance (HOMA-IR) was calculated by using the obtained insulin and fasting blood glucose values before neoadjuvant chemotherapy (fasting insulin × fasting glucose/405). We considered a cut-off of 2.5 for insulin resistance. The systemic inflammatory index (SII), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. RESULTS: Twenty-five patients had no insulin resistance. The most common pathologic subtype (56%) was hormone receptor (HR) positive and human epidermal growth factor receptor-2 (Her-2)-negative invasive ductal carcinoma. Sixteen (29%) patients had a pathological complete response (pCR). We found that the probability of pCR in patients with insulin resistance was 4.7 times lower than that in patients without insulin resistance [OR: 4.7 (95%CI 1.7-17.2), p = 0.01]. CONCLUSION: Our results revealed that insulin resistance may have a negative effect on pathological complete response (pCR) following neoadjuvant therapy particularly with hormone-positive and Her-2-negative cases of non-diabetic breast cancer.

Prognostic Value of the Pace of Tumor Progression as Assessed by Serial 18F-FDG PET/CT Scan and Liquid Biopsy in Refractory Colorectal Cancer: The CORIOLAN Trial.

INTRODUCTION: Decision making in refractory colorectal cancer (rCRC) is challenging, with limited data available to predict patient outcome. We conducted a study to assess the pace of cancer progression as a potential prognostic and decision tool. METHODS: CORIOLAN was a prospective, single-center, single-arm trial recruiting refractory CRC patients with an ECOG performance status of ≤1 and an estimated life expectancy of ≥12 weeks. 18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan and blood sample collection were carried out at baseline and after 2 weeks with no cancer treatment given between these timepoints. The primary objective was to evaluate the association between pace of cancer progression as defined by changes of the whole-body metabolically active tumor volume (WB-MATV) and overall survival (OS). Exploratory objectives included evaluation of the prognostic value of circulating cell-free DNA (cfDNA), circulating tumor cells (CTCs) and carcinoembryonic antigen (CEA). RESULTS: 47 eligible patients who had received a median number of 5 (range 2-8) prior treatments were enrolled. At the time of analysis, 45 deaths had occurred, with 26% of patients dying within 12 weeks. The median OS was 6.3 months (range 0.4-14.3). The median relative delta between WB-MATV at baseline and 2 weeks was +21%. Changes of WB-MATV, however, failed to predict OS (hazard ratio (HR) 1.3, p = 0.383). Similarly, no association was observed between changes of any of the circulating biomarkers investigated and prognosis. By contrast, high WB-MATV (4.2 versus 9.4 months; HR 3.1, p = 0.003), high CEA (4.4 versus 7.0 months; HR 1.9, p = 0.053), high cfDNA (4.7 versus 7.0 months; HR 2.2, p = 0.015) and high CTC count (3.3 versus 7.5 months; HR 6.5, p < 0.001) at baseline were associated with worse OS. CONCLUSIONS: In this study, approximately 1 out of 4 refractory CRC patients who were judged to have a life expectancy >12 weeks actually died within 12 weeks. Baseline assessment of WB-MATV, cfDNA, CTCs and CEA, but not early change evaluation of the same, may help to refine patient prognostication and guide management decisions.

Feasibility and clinical impact of routine molecular testing of gastrointestinal cancers at a tertiary centre with a multi-gene, tumor-agnostic, next generation sequencing panel.

BACKGROUND: High-throughput sequencing technologies are increasingly used in research but limited data are available on the feasibility and value of these when routinely adopted in clinical practice. MATERIAL AND METHODS: We analyzed all consecutive cancer patients for whom genomic testing by a 48-gene next-generation sequencing (NGS) panel (Truseq Amplicon Cancer Panel, Illumina) was requested as part of standard care in one of the largest Belgian cancer networks between 2014 and 2019. Feasibility of NGS was assessed in all study patients, while the impact of NGS on the decision making was analyzed in the group of gastrointestinal cancer patients. RESULTS: Tumor samples from 1064 patients with varying tumor types were tested, the number of NGS requests increasing over time (p < .0001). Success rate and median turnaround time were 91.4% and 12.5 days, respectively, both significantly decreasing over time (p ≤ .0002). Non-surgical sampling procedure (OR 7.97, p < .0001), tissue from metastatic site (OR 2.35, p = .0006) and more recent year of testing (OR 1.79, p = .0258) were independently associated with NGS failure. Excluding well-known actionable or clinically relevant mutations which are recommended by international guidelines and commonly tested by targeted sequencing, 57/279 (20.4%) assessable gastrointestinal cancer patients were found to have tumors harboring at least one actionable altered gene according to the OncoKB database. NGS results, however, had a direct impact on management decisions by the treating physician in only 3 cases (1.1%). CONCLUSIONS: Our findings confirm that NGS is feasible in the clinical setting with acceptably low failure rates and rapid turnaround time. In gastrointestinal cancers, however, NGS-based multiple-gene testing adds very little to standard targeted sequencing, and in routine practice the clinical impact of NGS panels including genes which are not routinely recommended by international guidelines remains limited.

QT interval prolongation related to afatinib treatment in a patient with metastatic non-small-cell lung cancer.

Afatinib improves survival in metastatic non-small-cell lung cancer driven by activating epidermal growth factor receptor mutations. QT interval prolongation is a possible side effect of targeted anticancer drugs, but this has not been reported before with afatinib. We report a case of metastatic pulmonary adenocarcinoma with epidermal growth factor receptor exon 19 deletion who was treated with first-line afatinib. The patient was started on afatinib with a total dose of 40 mg/day and experienced grade 3 (>500 ms) QT interval prolongation in the seventh week. Dose was interrupted and then reduced to 30 mg/day after the event repeated. QT prolongation occurred only once with the reduced dose and radiologic oligoprogression was detected. Local therapy was performed and afatinib was continued as 30 mg/day. To the best of our knowledge, this case marks the first QT interval prolongation associated with afatinib. It is prudent to perform a baseline cardiologic evaluation and electrocardiogram monitoring in non-small cell lung cancer patients treated with this drug.

Clinicopathologic Features of Gastroenteropancreatic Neuroendocrine Tumors: A Single-center Experience

Background: Gastroenteropancreatic neuroendocrine tumors, a heterogeneous group of neoplasms, originates from the neuroendocrine system of the gastrointestinal tract and pancreas. There are limited number of studies investigating neuroendocrine tumors in Turkey. Aims: To define the clinicopathologic, demographic, and survival features of patients with gastroenteropancreatic neuroendocrine tumors. Study Design: A retrospective observational cohort study. Methods: We reviewed hospital records of patients and data was analyzed retrospectively. We investigated the clinical, pathological, survival features, and prognosis of patients with gastroenteropancreatic neuroendocrine tumors (n=128) admitted to the medical oncology department between year 2003 and 2014. Survival estimation was performed by the Kaplan-Meier method. Univariate and multivariate Cox regression models were utilized to investigate the prognostic factors for survival. Results: Of 128 patients with gastroenteropancreatic neuroendocrine tumors, 61 (47.7%) were female and 67 (52.3%) were male. The most common site of the tumor was stomach (36.7%), while the most common stage of tumor at diagnosis was stage 4 (40.9%). The median follow-up period was 37 months, while the 3- and 5-year overall survival rates were 78% and 69%, respectively. The factors significantly affecting overall survival rate were clinical stage, grade, presence of metastasis at diagnosis, and Ki-67 proliferation index. These factors were associated with the 3- and 5-year overall survival rate. Moreover, grade (hazard ratio: 8.34, 95% confidence interval: 2.16-32.22, p=0.01) and presence of metastasis at diagnosis (hazard ratio: 3.18, 95% confidence interval: 1.30-7.77, p=0.01) independently predicted overall survival in multivariate model following adjustment for age and gender. Conclusion: Higher-grade and presence of metastasis at diagnosis are negative independent prognostic indicators of survival in patients with gastroenteropancreatic neuroendocrine tumors.

Impact of the Charlson Comorbidity Index on dose-limiting toxicity and survival in locally advanced and metastatic renal cell carcinoma patients treated with first-line sunitinib or pazopanib.

BACKGROUND: Anti-angiogenic tyrosine kinase inhibitors, sunitinib and pazopanib, have proven efficacy in advanced renal cell carcinoma, with specific adverse events occurring during treatment process. Comorbidities can reflect functional status and have prognostic value in oncology patients. We aimed to assess the association of the Charlson Comorbidity Index with severe toxicities and mortality in renal cell carcinoma cases treated with front-line sunitinib or pazopanib. METHODS: Files of locally advanced and metastatic renal cell carcinoma patients who received first-line sunitinib or pazopanib were retrospectively examined. Charlson Comorbidity Index of each patient was calculated. Patients were also stratified into Memorial Sloan-Kettering Cancer Center risk groups. Predictors of dose-limiting toxicity were evaluated with binomial logistic regression analysis. Univariate and multivariate Cox regression models were utilized to determine prognostic factors for survival. RESULTS: The study included 102 patients, 64 were treated with first-line sunitinib and 38 with pazopanib. In 42 patients (41.9%), Charlson Comorbidity Index was 9 or more. Dose-limiting toxicities were significantly more frequent in Charlson Comorbidity Index ≥9 group (69% vs. 40%, p = 0.004), and Charlson Comorbidity Index independently predicted dose-limiting toxicity (Hazard ratio (HR) = 4.30, p = 0.002). After adjusting for other variables, a Charlson Comorbidity Index of ≥9 is also a significant prognostic factor for progression-free (HR = 1.76, p = 0.02) and overall survival (HR = 1.75, p = 0.03). CONCLUSIONS: Charlson Comorbidity Index may be a valuable method to estimate prognosis and optimize therapy in patients with advanced renal cell carcinoma receiving first-line sunitinib or pazopanib.

PD-1 and PD-L1 inhibitors in oesophago-gastric cancers.

Oesophago-gastric cancers (OGCs) are aggressive tumours. While better peri-operative strategies, increased number of cytotoxic agents and availability of targeted therapies have improved survival, there remains an unmet need for novel treatment approaches. Immune checkpoint inhibitors (ICIs) have marked a new era in cancer management with unprecedented results in several malignancies. Although OGC lagged behind other solid tumours, evidence has increasingly accumulated supporting the contention that modulation of the anti-cancer host immune response may be beneficial for at least some patients. Many trials have been completed in Eastern and Western countries, some of these leading to the approval of ICIs in the refractory setting, and favorable opinion from regulatory agencies is expected also in treatment-naïve, advanced OGC. Furthermore, studies are evaluating ICIs in the early stage setting and exploring the potential of combination treatments. In this article we discuss the biological bases underlying the successful development of ICIs in OGC and review the available data on PD-1 and PD-L1 monoclonal antibodies in this disease. Also, we present ongoing clinical trials of these ICIs that could shape the future treatment landscape of OGC.

Comparison of two different carboplatin and weekly paclitaxel schedule in elderly advanced non-small cell lung cancer patients.

PURPOSE: In this study our aim was to compare efficacy and toxicity profiles of two different schedule of carboplatin-paclitaxel regimen in elderly advanced non-small cell lung cancer (NSCLC) patients. METHODS: Data from the charts of 59 elderly patients with metastatic NSCLC, treated with weekly paclitaxel combined with two different schedule of carboplatin were collected retrospectively from three medical oncology centers in Turkey between September 2002 to March 2018. No prior systemic therapy or radiotherapy was allowed. Brain metastases were not considered as exclusion criteria unless symptomatic. Patients were analyzed in two treatment groups; CP3 (who received 3 weekly carboplatin and weekly paclitaxel), and CP1 (weekly carboplatin and weekly paclitaxel). Overall survival (OS) was the primary endpoint of the study. Secondary end points were as follows: progression free survival (PFS), response rates (RR), grade 3-4 toxicities, skipped cycles, dose reductions, and treatment discontinuation rates. RESULTS: Twenty-four patients received 3 weekly carboplatin and weekly paclitaxel schedule (CP3) while weekly carboplatin and weekly paclitaxel schedule (CP1) was performed in 35 patients. CP3 had a median OS of 14 months whereas CP1 had 9 months of median OS (p = 0.084). Both treatments (CP3 vs CP1) had similar median PFS (7 months vs 4 months, p = 0.109) and objective RR (20.9% vs 29.4%, p = 0.465). There was an increased incidence of grade 3-4 anemia and grade 3-4 neutropenia in CP3 compared to CP1 (p = 0.003 in both), but no major differences in febrile neutropenia and infection toxicity profiles (p = 0.289 and p = 0.770, respectively). Weekly schedule (CP1) had a tendency of increased grade 3-4 neurotoxicity (33.3% vs 42.9%, p = 0.461). CONCLUSION: Weekly carboplatin and paclitaxel might be more tolerable and is as effective as 3 weekly carboplatin and weekly paclitaxel schedule in metastatic elderly NSCLC patients.

Chordoma: a case series and review of the literature.

BACKGROUND: Chordoma is a rare malignant tumor of the skull base and axial skeleton, with an incidence of less than 0.1/100,000 per year. Patients with advanced chordoma have a poor prognosis due to locoregional recurrence with infiltration and destruction of surrounding bone and soft tissue. Cytotoxic chemotherapy or other systemic therapies have not been proven to be effective for these diseases. Therefore, several molecularly targeted therapies have been proposed as potentially beneficial, including tyrosine kinase inhibitors such as imatinib, sorafenib, lapatinib, and others. CASE PRESENTATION: We present three cases of advanced chordoma treated with molecular targeted therapies: a 52-year-old Caucasian man, a 72-year-old Caucasian woman, and a 38-year-old Caucasian woman. CONCLUSIONS: Chordoma has few systemic treatment options and they have limited benefit. Randomized trials with large patient numbers are unfeasible in this rare disease. Targeted therapy might be a reasonable alternative treatment for chordoma. Still, new treatment strategies are needed for this rare disease.