Olaparib with or without bevacizumab versus bevacizumab plus a fluoropyrimidine as maintenance therapy in advanced colorectal cancer: The randomized phase 3 LYNK-003 study.

BACKGROUND: The randomized, open-label, phase III LYNK-003 study assessed the efficacy of first-line maintenance olaparib, alone or in combination with bevacizumab, versus bevacizumab plus a fluoropyrimidine in participants with unresectable or metastatic colorectal cancer (mCRC). We present results of the prespecified interim futility analysis. METHODS: Eligible participants were ≥18 years of age with unresectable or mCRC that had not progressed after induction with first-line bevacizumab plus 5-fluorouracil plus oxaliplatin plus leucovorin (FOLFOX) or capecitabine plus oxaliplatin (CAPOX). Participants were randomly assigned 1:1:1 to olaparib plus bevacizumab, olaparib alone, or bevacizumab plus a fluoropyrimidine (5-fluorouracil or capecitabine). The primary end point was progression-free survival (PFS) per RECIST v1.1 by central review. RESULTS: Between August 2020 and May 2022, 309 participants were assigned to olaparib plus bevacizumab (n = 104), olaparib (n = 107), or bevacizumab plus fluoropyrimidine (n = 98). At interim analysis, with a median follow-up of 7.6 months (range 0.1-19.7 months), the median PFS was 3.7 months (95% CI 2.8-5.3) with olaparib plus bevacizumab (HR 1.52; 95% CI 1.02-2.27; P = 0.982) and 3.5 months (95% CI 2.0-3.7) with olaparib (HR 2.11; 95% CI 1.39-3.18; P = 0.999) versus 5.6 months (95% CI 3.8-5.9) with bevacizumab plus fluoropyrimidine. Treatment-related adverse events occurred in 64 (62%), 52 (50%), and 57 (59%) participants, respectively. There were no treatment-related deaths. CONCLUSION: The LYNK-003 study was stopped prematurely as criteria for futility were met. Maintenance olaparib with or without bevacizumab did not demonstrate clinical efficacy compared with bevacizumab plus a fluoropyrimidine. GOV REGISTRATION: NCT04456699.

Pre-chemoradiotherapy high platelet counts predict jaw osteoradionecrosis in locally advanced nasopharyngeal carcinoma patients.

INTRODUCTION: This retrospective study aimed to investigate if pretreatment platelet (PLT) levels can predict the risk of osteoradionecrosis of the jaw (ORNJ) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) who received concurrent chemoradiotherapy (CCRT). MATERIAL &METHODS: ORNJ instances were identified from LA-NPC patients' pre- and post-CCRT oral exam records. All pretreatment PLT values were acquired on the first day of CCRT. Receiver operating characteristic curve analysis was used to determine the optimal PLT cutoff that divides patients into two subgroups with distinctive ORNJ rates. The primary outcome measure was the association between pretreatment PLT values and ORNJ incidence rates. RESULTS: The incidence of ORNJ was 8.8 % among the 240 LA-NPC patients analyzed. The ideal pre-CCRT PLT cutoff which divided the patients into two significantly different ORNJ rate groups was 285,000 cells/µL (PLT ≤ 285,000 cells/µL (N = 175) vs. PLT > 285,000 cells/µL (N = 65)). A comparison of the two PLT groups revealed that the incidence of ORNJ was substantially higher in patients with PLT > 285,000 cells/L than in those with PLT≤285,000 cells/L (26.2% vs. 2.3 %; P < 0.001). The presence of pre-CCRT ≥3 tooth extractions, any post-CCRT tooth extractions, mean mandibular dose ≥ 34.1 Gy, mandibular V57.5 Gy ≥ 34.7 %, and post-CCRT tooth extractions > 9 months after CCRT completion were also associated with significantly increased ORNJ rates. A multivariate Cox regression analysis demonstrated that each characteristic had an independent significance on ORNJ rates after CCRT. CONCLUSION: An affordable and easily accessible novel biomarker, PLT> 285,000 cells/L, may predict substantially higher ORNJ rates after definitive CCRT in individuals with LA-NPC.

Predictive potential of pan-immune-inflammation value / hemoglobin index as biomarker for osteoradionecrosis risk in locally advanced nasopharyngeal carcinomas.

OBJECTIVE: We aimed to investigate whether the Pan-Immune-Inflammation-Value/Hemoglobin (PIV/Hb) index could predict the risk of osteoradionecrosis (ORN) in patients receiving concurrent chemoradiotherapy (CCRT) for locally advanced nasopharyngeal cancer (LA-NPC). MATERIALS AND METHODS: This retrospective analysis included LA-NPC patients who underwent CCRT and pre-CCRT oral exams at our institution's Departments of Radiation Oncology and Dentistry between January 2010 and December 2022. The relationship between ORN rates and PIV-Hb levels was explored using receiver operating characteristic curve analysis. The primary objective was to establish a correlation between pre-CCRT PIV-Hb levels and ORN rates, while the secondary objective was to identify other risk factors for ORN. RESULTS: Of 249 eligible patients, 21 (8.4 %) were diagnosed with ORN. The optimal pre-CCRT PIV/Hb cutoff was 73.8, which divided patients into two subgroups with distinctive ORN risk estimates: Group 1: PIV/Hb < 73.8 (N = 206), and Group 2: PIV/Hb ≥ 73.8 (N = 43). The results of the comparative analysis indicated that the cohort with PIV/Hb ≥ 73.8 exhibited substantially higher rates of ORN than the PIV/Hb < 73.8 cohort (44.2 % vs. 1.0 %; P < 0.001). The multivariate logistic regression analysis indicated that the pretreatment PIV/Hb ≥ 73.8 was independently associated with higher ORN rates (P < 0.001). CONCLUSION: The results of our current investigation indicate that higher levels of pretreatment PIV/Hb were associated with a significant independent increase in ORN rates in LA-NPC patients who received CCRT.

The Use of Pre-Chemoradiotherapy Total Masseter Muscle Volume as a Novel Predictor of Radiation-Induced Trismus in Locally Advanced Nasopharyngeal Carcinoma Patients.

BACKGROUND: We sought to determine whether pretreatment total masseter muscle volume (TMMV) measures can predict radiation-induced trismus (RIT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving concurrent chemoradiotherapy (C-CRT). METHODS: We retrospectively reviewed the medical records of LA-NPC patients who received C-CRT and had pretreatment maximum mouth openings (MMO) greater than 35 mm. MMO of 35 mm or less after C-CRT were considered RIT. We employed receiver operating characteristic (ROC) curve analysis to explore the correlation between pre-treatment TMMV readings and RIT status. RESULTS: Out of the 112 eligible patients, 22.0% of them received a diagnosis of RIT after C-CRT. The optimal TMMV cutoff that was significantly linked to post-C-CRT RIT rates was determined to be 35.0 cc [area under the curve: 79.5%; sensitivity: 75.0%; and specificity: 78.6%; Youden index: 0.536] in the ROC curve analysis. The incidence of RIT was significantly higher in patients with TMMV ≤ 5.0 cc than in those with TMMV > 35.0 cc [51.2% vs. 8.7%; Odds ratio: 6.79; p < 0.001]. A multivariate logistic regression analysis revealed that pre-C-CRT MMO ≤ 41.6 mm (p = 0.001), mean masticatory apparatus dose V56.5 ≥ 34% group (p = 0.002), and TMMV ≤ 35 cc were the independent predictors of significantly elevated rates of RIT. CONCLUSION: The presence of a smaller pretreatment TMMV is a reliable and independent novel biological marker that can confidently predict higher RIT rates in LA-NPC patients who receive C-CRT.

Worth of pan-immune-inflammation value in trismus prediction after concurrent chemoradiotherapy for nasopharyngeal carcinomas.

OBJECTIVE: Radiation-induced trismus (RIT), one of the rare but serious side effects of concurrent chemoradiotherapy (C-CRT), is difficult to predict with high accuracy. We aimed to examine whether the pretreatment pan-immune-inflammation value (PIV) measures predict RIT in patients with locally advanced nasopharyngeal carcinoma (LA-NPC) receiving C-CRT. METHODS: Data of patients with LA-NPC who underwent C-CRT and had maximum mouth openings (MMO) > 35 mm were reviewed. Any MMO of 35 mm or less after C-CRT was considered RIT. All PIV values were computed using the complete blood count test results: PIV = (Platelets × Monocytes × Neutrophils) ÷ Lymphocytes. The receiver operating characteristic analysis was employed to dissect a possible association between pre-treatment PIV readings and RIT status. Confounding variables were tested for their independent relationship with the RIT rates using logistic regression analysis. RESULTS: The research comprised 223 participants, and RIT was diagnosed in 46 (20.6%) at a median time from C-CRT to RIT of 10 months (range: 5-18 months). Pre-C-CRT PIV levels and RIT rates were analyzed using receiver operating characteristic curve analysis, with 830 being the optimal cutoff (area under the curve: 92.1%; sensitivity: 87.5%; specificity: 85.5%; Youden index: 0.730). RIT was significantly more prevalent in the PIV > 830 cohort than its PIV ≤ 830 counterpart (60.3% vs. 5%; hazard ratio 5.79; P < 0.001). Multivariate logistic regression analysis revealed that advanced T-stage (P = 0.004), masticatory apparatus dose V58Gy≥%32 (P = 0.003), and PIV > 830 (P < 0.001) were independently linked with significantly elevated rates of RIT. CONCLUSION: The presence of elevated pre-C-CRT PIV is a unique biological marker that independently predicts increased RIT rates in LA-NPC undergoing C-CRT.

High pre-chemoradiotherapy pan-immune-inflammation value levels predict worse outcomes in patients with stage IIIB/C non-small-cell lung cancer.

BACKGROUND AND OBJECTIVES: We explored the prognostic usefulness of the pan-immune-inflammation value (PIV) in patients with stage IIIB/C non-small-cell lung cancer (NSCLC) who underwent concurrent chemoradiotherapy (CCRT). METHODS AND PATIENTS: For all patients, the PIV was calculated using platelet (P), monocyte (M), neutrophil (N), and lymphocyte (L) measures obtained on the first day of CCRT: PIV = P × M × N ÷ L. Using receiver operating characteristic (ROC) curve analysis, we searched for the existence of an ideal cutoff that may partition patients into two groups with unique progression-free- (PFS) and overall survival (OS) results. The primary endpoint of this retrospective cohort research was to determine whether there were any significant relationships between pretreatment PIV measures and post-CCRT OS outcomes. RESULTS: The present research included a total of 807 stage IIIB/C NSCLC patients. According to ROC curve analysis, the ideal PIV cutoff was 516 [area under the curve (AUC): 67.7%; sensitivity: 66.4%; specificity: 66.1%], which divided the whole cohort into two: low PIV (L-PIV: PIV < 516; N = 436) and high PIV (H-PIV: PIV ≥ 516; N = 371). The comparisons between the PIV groups indicated that either the median PFS (9.2 vs. 13.4 months; P < 0.001) or OS (16.7 vs. 32.7 months; P < 0.001) durations in the H-PIV group were substantially inferior to their L-PIV counterpart. Apart from the H-PIV (P < 0.001), the N3 nodal stage (P = 0.006), IIIC disease stage (P < 0.001), and receiving only one cycle of concurrent chemotherapy (P = 0.005) were also determined to be significant predictors of poor PFS (P < 0.05, for each) and OS (P < 0.05, for each) outcomes in univariate analysis. The multivariate analysis findings revealed that all four variables had independent negative impacts on PFS (P < 0.05, for each) and OS (P < 0.05, for each). CONCLUSIONS: The findings of this hypothesis-generating retrospective analysis claimed that the novel PIV was an independent and steadfast predictor of PFS and OS in stage IIIB/C NSCLC patients.

Predicting Teeth Extraction after Concurrent Chemoradiotherapy in Locally Advanced Nasopharyngeal Cancer Patients Using the Novel GLUCAR Index.

To evaluate the value of the newly created GLUCAR index in predicting tooth extraction rates after concurrent chemoradiotherapy (C-CRT) in locally advanced nasopharyngeal carcinomas (LA-NPCs). Methods: A total of 187 LA-NPC patients who received C-CRT were retrospectively analyzed. The GLUCAR index was defined as 'GLUCAR = (Fasting Glucose × CRP/Albumin Ratio) by utilizing measures of glucose, C-reactive protein (CRP), and albumin obtained on the first day of C-CRT. Results: The optimal GLUCAR cutoff was 31.8 (area under the curve: 78.1%; sensitivity: 70.5%; specificity: 70.7%, Youden: 0.412), dividing the study cohort into two groups: GLUCAR ˂ 1.8 (N = 78) and GLUCAR ≥ 31.8 (N = 109) groups. A comparison between the two groups found that the tooth extraction rate was significantly higher in the group with a GLUCAR ≥ 31.8 (84.4% vs. 47.4% for GLUCAR ˂ 31.8; odds ratio (OR):1.82; p < 0.001). In the univariate analysis, the mean mandibular dose ≥ 38.5 Gy group (76.5% vs. 54.9% for <38.5 Gy; OR: 1.45; p = 0.008), mandibular V55.2 Gy group ≥ 40.5% (80.3 vs. 63.5 for <40.5%, p = 0.004, OR; 1.30), and being diabetic (71.8% vs. 57.9% for nondiabetics; OR: 1.23; p = 0.007) appeared as the additional factors significantly associated with higher tooth extraction rates. All four characteristics remained independent predictors of higher tooth extraction rates after C-CRT in the multivariate analysis (p < 0.05 for each). Conclusions: The GLUCAR index, first introduced here, may serve as a robust new biomarker for predicting post-C-CRT tooth extraction rates and stratifying patients according to their tooth loss risk after treatment.

Pretreatment Masseter Muscle Volume Predicts Survival in Locally Advanced Nasopharyngeal Carcinoma Patients Treated with Concurrent Chemoradiotherapy.

BACKGROUND AND PURPOSE: Muscle loss is a significant indicator of cancer cachexia and is associated with a poor prognosis in cancer patients. Given the absence of comparable studies, the current retrospective study sought to examine the correlation between the total masseter muscle volume (TMMV) before treatment and the survival outcomes in locally advanced nasopharyngeal cancer (LA-NPC) patients who received definitive concurrent chemoradiotherapy (CCRT). METHODS: A three-dimensional segmentation model was used to determine the TMMV for each patient by analyzing pre-CCRT magnetic resonance imaging. The optimal TMMV cutoff values were searched using receiver operating characteristic (ROC) curve analyses. The primary and secondary endpoints were the relationship between the pre-CCRT TMMV measures and overall survival (OS) and progression-free survival (PFS), respectively. RESULTS: Ninety-seven patients were included in this study. ROC curve analyses revealed 38.0 cc as the optimal TMMV cutoff: ≤38.00 cc (n = 42) and >38.0 cc (n = 55). Comparisons between the two groups showed that the TMMV>38.0 cc group had significantly longer PFS [Not reached (NR) vs. 28; p < 0.01] and OS (NR vs. 71; p < 0.01) times, respectively. The results of the multivariate analysis demonstrated that the T-stage, N-stage, number of concurrent chemotherapy cycles, and TMMV were independent associates of PFS (p < 0.05 for each) and OS (p < 0.05 for each) outcomes, respectively. CONCLUSION: The findings of the current retrospective research suggest that pretreatment TMMV is a promising indicator for predicting survival outcomes in LA-NPC patients receiving definitive CCRT.

The Prognostic Value of the Novel Global Immune-Nutrition-Inflammation Index (GINI) in Stage IIIC Non-Small Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy.

BACKGROUND: We sought to determine the prognostic value of the newly developed Global Immune-Nutrition-Inflammation Index (GINI) in patients with stage IIIC non-small cell lung cancer (NSCLC) who underwent definitive concurrent chemoradiotherapy (CCRT). METHODS: This study was conducted on a cohort of 802 newly diagnosed stage IIIC NSCLC patients who underwent CCRT. The novel GINI created first here was defined as follows: GINI = [C-reactive protein × Platelets × Monocytes × Neutrophils] ÷ [Albumin × Lymphocytes]. The receiver operating characteristic (ROC) curve analysis was used to determine the optimal pre-CCRT GINI cut-off value that substantially interacts with the locoregional progression-free (LRPFS), progression-free (PFS), and overall survival (OS). RESULTS: The optimal pre-CCRT GINI cutoff was 1562 (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%; Youden index: 0.406). Patients presenting with a GINI ≥ 1562 had substantially shorter median LRPFS (13.3 vs. 18.4 months; p < 0.001), PFS (10.2 vs. 14.3 months; p < 0.001), and OS (19.1 vs. 37.8 months; p < 0.001) durations than those with a GINI < 1562. Results of the multivariate analysis revealed that the pre-CCRT GINI ≥ 1562 (vs. <1562), T4 tumor (vs. T3), and receiving only 1 cycle of concurrent chemotherapy (vs. 2-3 cycles) were the factors independently associated with poorer LRPS (p < 0.05 for each), PFS (p < 0.05 for each), and OS (p < 0.05 for each). CONCLUSION: The newly developed GINI index efficiently divided the stage IIIC NSCLSC patients into two subgroups with substantially different median and long-term survival outcomes.

High Measures of Pre-Chemoradiotherapy Platelet-to-Albumin Ratio Indicates Poor Prognosis in Locally Advanced Pancreatic Cancer Patients.

Purpose: In a lack of similar research, we meant to retrospectively investigate the prognostic significance of pre-chemoradiotherapy (C-CRT) platelet-to-albumin ratio (PAR) on the survival results of locally advanced unresectable pancreatic adenocarcinoma (LAPC) patients. Patients and Methods: The present analysis included 139 LAPC patients who received C-CRT in total. The utility of pre-C-CRT cutoff(s) reshaping survival data was explored using receiver operating characteristic (ROC) curve analysis. The primary and secondary objectives were the associations between PAR levels and overall survival (OS) and progression-free survival (PFS) outcomes. Results: At a median follow-up of 15.7 months (95% CI: 11.6-19.8), the overall cohort's median and 5-year OS rates were 14.4 months (95% CI: 11.8-17) and 14.7%, respectively, while the corresponding PFS rates were 7.8 months (95% CI: 6.5-9.1) and 11.2%. Because the ROC curve analysis found 4.9 as the optimal PAR cutoff for both OS and PFS [area under the curve (AUC): 75.4%; sensitivity: 72.4%; specificity: 70.3%], we divided the patients into two PAR cohorts: PAR<4.9 (N=60) and PAR≥4.9 (N=79). Comparative analysis per PAR group exhibited significantly worse OS (11.2 vs 18.6 months, and 9.8% vs 20.9% at 5 years, P=0.003) and DFS (7 vs 14.3 months, and 7.6% vs 16.2% at 5 years, P=0.001) with PAR≥4.9 versus PAR<4.9, respectively. In multivariate analysis, the N0 nodal status, CA 19-9≤90 U/mL, and PAR<4.9 were found to be independent predictors of improved OS and PFS. Conclusion: The pre-C-CRT high PAR (≥4.9) robustly and independently prognosticated significantly worse OS and PFS results in inoperable LAPC patients who underwent definitive C-CRT.

Cisplatin plus paclitaxel and bevacizumab versus carboplatin plus paclitaxel and bevacizumab for the first-line treatment of metastatic or recurrent cervical cancer.

OBJECTIVE: Cisplatin-paclitaxel and bevacizumab is a frequently used treatment regimen for metastatic or recurrent cervical cancer, and carboplatin-paclitaxel and bevacizumab are also among the recommended regimens. In this study we aimed to evaluate the efficacy of these two regimens for the treatment of metastatic or recurrent cervical cancer. METHODS: Patients with metastatic or recurrent cervical cancer treated with cisplatin-paclitaxel and bevacizumab or carboplatin-paclitaxel and bevacizumab were retrospectively evaluated in this study. The clinical and demographic characteristics of patients in each group were evaluated. Median overall survival, progression-free survival, and response rates between the two groups were compared. RESULTS: A total of 250 patients were included. Overall, the numbers of patients with recurrent disease and metastatic disease were 159 and 91, respectively. The most common histologic subtype was squamous cell carcinoma (83.2%). The median duration of follow-up was 13.6 (range 0.5-86) months. The median progression-free survival was 10.5 (95% CI 9.0 to 11.8) months in the cisplatin-paclitaxel and bevacizumab group (group 1), and 10.8 (95% CI 8.6 to 13.0) months in the carboplatin-paclitaxel and bevacizumab group (group 2) (HR 1.20; 95% CI 0.88 to 1.63; p=0.25). The median overall survival was 19.1 (95% CI 13.0 to 25.1) months in group 1 and 18.3 (95% CI 15.3 to 21.3) months in group 2 (HR 1.28; 95% CI 0.91 to 1.80; p=0.15). CONCLUSIONS: There is no survival difference between cisplatin or carboplatin combined with paclitaxel and bevacizumab in metastatic or recurrent cervical cancer.

Cetuximab-induced rash is associated with overall survival in patients with recurrent/metastatic squamous cell carcinoma of head and neck.

PURPOSE: In this study, we looked for whether treatment-induced rash predicts treatment efficacy in patients with recurrent/metastatic HNSCC treated with Cetuximab and chemotherapy. METHODS: Patients who were treated with platinum-based chemotherapy and cetuximab for the first line treatment of recurrent/metastatic HNSCC were recruited. Presence of rash, hypomagnesemia, hypopotassemia, anemia, neutropenia, thrombocytopenia during treatment and treatment response, date of progression, date of last visit and death were recorded. RESULTS: A total of 138 patients' data were available for analysis. Any grade of rash was detected in 57 (44.5%) of the patients. The incidence of rash was significantly higher in patients with objective response than in patients with disease progression (%56.8 vs %14.3, p < 0.001). Progression free survival was 7.06 months (4.98-9.15) in patients treated with cetuximab and chemotherapy as first line treatment. In the multivariate analysis; rash was significantly correlated with longer PFS (HR 2.136; 95% CI 1.067-4.278; p = 0.032). Progression free survival was 9.65 months in patients who experienced rash, and 6.02 months in patients without rash, (p = 0.019, log-rank test). Overall survival was 11.24 months (9.65-12.82). In multivariate analysis, the survival of patients with rash was significantly longer than patients without rash (HR 1.954; 95% CI 1.162-3.285; p = 0.012). Overall survival was 15.08 months in patients who experienced rash, and 8.61 months in patients without rash (p = 0.05, log-rank test). CONCLUSION: Cetuximab-induced rash is associated with better ORR and longer PFS and OS in patients with recurrent/metastatic HNSCC treated with Cetuximab and platinum-based chemotherapy.

Prechemoradiotherapy Systemic Inflammation Response Index Stratifies Stage IIIB/C Non-Small-Cell Lung Cancer Patients into Three Prognostic Groups: A Propensity Score-Matching Analysis.

PURPOSE: We explored the prognostic influence of the systemic inflammation response index (SIRI) on the survival outcomes of stage IIIB/C non-small-cell lung cancer (NSCLC) patients who underwent concurrent chemoradiotherapy. METHODS: Present propensity score-matching (PSM) analysis comprised 876 stage IIIB/C NSCLC patients who received 1-3 cycles of platinum-based doublets concurrent with thoracic radiotherapy from 2007 to 2017. The primary and secondary objectives were the relationships between the SIRI values and overall (OS) and progression-free survival, respectively. Propensity scores were calculated for SIRI groups to adjust for confounders and to facilitate well-balanced comparability between the SIRI groups by creating 1 : 1 matched study groups. RESULTS: The receiver operating characteristic curve analysis identified an optimal SIRI cutoff at 1.9 for OS (AUC: 78.8%; sensitivity: 73.7%; specificity: 70.7%) and PFS (AUC: 80.5%; sensitivity: 75.8%; specificity: 72.9%) and we grouped the patients into two PSM cohorts: SIRI < 1.9 (N = 304) and SIRI ≥ 1.9 (N = 304), respectively. The SIRI ≥ 1.9 cohort had significantly worse median OS (P < 0.001) and PFS (P < 0.001) than their SIRI < 1.9 companions. The further combination of SIRI with disease stage exhibited that the SIRI-1 (IIIB and SIRI < 1.9) and SIRI-3 (IIIC and SIRI ≥ 1.9) cohorts had the best and worst outcomes, respectively, with SIRI-2 cohort (IIIB and SIRI ≥ 1.9 or IIIC and SIRI < 1.9) being remained in between (P < 0.001 for OS and PFS, separately). In multivariate analysis, the two- and three-laddered stratifications per the 1.9 cutoffs and SIRI groups retained their independent significance, individually. CONCLUSIONS: The SIRI ≥ 1.9 independently prognosticated significantly worse OS and PFS results and plated the stage IIIB/C patients into three fundamentally distinct prognostic groups.

Baseline Low Prognostic Nutritional Index Predicts Poor Survival in Locally Advanced Nasopharyngeal Carcinomas Treated With Radical Concurrent Chemoradiotherapy.

BACKGROUND: To retrospectively assess the impact of prognostic nutritional index (PNI) on survival outcomes of patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated with concurrent chemoradiotherapy (CCRT). METHODS: This study incorporated 154 patients with LA-NPC who received exclusive cisplatinum-based CCRT. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of pretreatment PNI cutoffs influencing survival results. The primary end point was the interaction between the overall survival (OS) and PNI values, while cancer-specific survival (CSS) locoregional progression-free survival (LR-PFS), distant metastasis-free survival (DMFS), and PFS were the secondary end points. RESULTS: A rounded PNI cutoff value of 51 was identified in ROC curve analyses to exhibit significant link with CSS, OS, DMFS, and PFS outcomes, but not LR-PFS. Patients grouping per PNI value (≥51 [N = 95] vs <51 [N = 49]) revealed that PNI < 51 group had significantly shorter median CSS (P < .001), OS (P < .001), DMFS (P < .001), and PFS (P < .001) times than the PNI ≥ 51 group, and the multivariate results confirmed the PNI < 51 as an independent predictor of poor outcomes for each end point (P < .05 for each). The unfavorable impact of the low PNI was also continued at 10-year time point with survival rates of 77.9% versus 42.4%, 73.6% versus 33.9%, 57.9% versus 27.1%, and 52.6% versus 23.7% for CSS, OS, DMFS, and PFS, respectively. Additionally, we found that PNI < 51 was significantly associated with higher rates of weight loss >5% over past 6 months (49.2% versus 11.6%; P = .002) compared to PNI < 51 group. CONCLUSION: Low pre-CCRT PNI levels were independently associated with significantly reduced CSS, OS, DMFS, and PFS outcomes in patients with LA-NPC treated with definitive CCRT.

Systemic Inflammation Response Index Predicts Survival Outcomes in Glioblastoma Multiforme Patients Treated with Standard Stupp Protocol.

OBJECTIVES: We endeavored to retrospectively assess the prognostic merit of pretreatment systemic immune response index (SIRI) in glioblastoma multiforme (GBM) patients who underwent postoperative partial brain radiotherapy (RT) and concurrent plus adjuvant temozolomide (TMZ), namely, the Stupp protocol. METHODS: The records of 181 newly diagnosed GBM patients who received the postoperative Stupp protocol were retrospectively analyzed. The SIRI value for each eligible patient was calculated by utilizing the platelet, neutrophil, and lymphocyte measures obtained on the first day of treatment: SIRI = Neutrophils × Monocytes/Lymphocytes. The ideal cutoff values for SIRI connected with the progression-free- (PFS) and overall survival (OS) results were methodically searched through using the receiver operating characteristic (ROC) curve analysis. Primary and secondary end-points constituted the potential OS and PFS distinctions among the SIRI groups, respectively. RESULTS: The ROC curve analysis labeled the ideal SIRI cutoffs at 1.74 (Area under the curve (AUC): 74.9%; sensitivity: 74.2%; specificity: 71.4%) and 1.78 (AUC: 73.6%; sensitivity: 73.1%; specificity: 70.8%) for PFS and OS status, individually. The SIRI cutoff of 1.78 of the OS status was chosen as the common cutoff for the stratification of the study population (Group 1: SIRI ≤ 1.78 (N = 96) and SIRI > 1.78 (N = 85)) and further comparative PFS and OS analyses. Comparisons between the two SIRI cohorts manifested that the SIRI ≤ 1.78 cohort had altogether significantly superior median PFS (16.2 versus 6.6 months; P < 0.001) and OS (22.9 versus 12.2 months; P < 0.001) than its SIRI > 1.78 counterparts. The results of multivariate Cox regression analyses ratified the independent and significant alliance between a low SIRI and longer PFS (P < 0.001) and OS (P < 0.001) durations, respectively. CONCLUSIONS: Present results firmly counseled the pretreatment SIRI as a novel, sound, and independent predictor of survival outcomes in newly diagnosed GBM patients intended to undergo postoperative Stupp protocol.

Half-dose bevacizumab experience in relapsed ovarian cancer patients in Turkey due to formal regulations: similar effectiveness with lower rate of hypertension.

PURPOSE: Ovarian cancer is the fifth leading cause of cancer related death in women. Platin-based doublet regimens plus bevacizumab is standard treatment in relapse. Due to formal regulation of Turkish Ministry of Health, adjuvant bevacizumab has not been reimbursed and clinicians can use bevacizumab at a dose of 7.5 mg/kg/3wk in platin-resistant and sensitive relapse settings. The primary aim of this study was to evaluate 7.5 mg/kg/3wk bevacizumab dosing in platin-resistant and sensitive relapse ovarian cancer and compare these findings with the current literature. METHODS: A total of 106 patients with relapsed ovarian cancer and treated with bevacizumab (bevacizumab is not reimbursed as a part of adjuvant treatment in Turkey) on their first relapse were included. RESULTS: At a median follow-up of 32.1 months (5.3-110.8), 56 (52.8%) patients died. Progression-free survival (PFS) and overall survival (OS) were estimated at 18.8 months (14.4-23.3) vs 29.7 months (24.3-35.1) of the whole group overall survival. We observed that 78.4% of patients treated with primary surgery without neoadjuvant treatment and 59 (57.8%) out of the 102 patients with debulking surgery relapsed. A significant number of patients (81%) treated with primary surgery without neoadjuvant treatment and 59 (76.6 %) had secondary debulking surgery at relapse. In relapse, 38 patients were treated with single agent liposomal doxorubicin (LPD) plus bevacizumab. On the other hand, 68 patients were treated with carboplatin and LPD plus bevacizumab. Multivariate analysis failed to show any clinicopathological characteristics with significant effect on PFS. However, cytoreductive surgery at relapse showed significant effect on OS. Bevacizumab-related toxicities were detected in 23 (21.7%) patients; hypertension, pulmonary embolism, perforation, and other toxicities (nephrotic syndrome in 2, osteonecrosis in 2, cerebrovascular and cardiac ischemia in 3 patients) were seen in 12 (11.3%), 3 (2.8%), 1 (0.9%) and 7 (6.6%) patients, respectively. CONCLUSIONS: In conclusion, our findings showed that 7.5 mg/kg/3week dosing of bevacizumab in relapsed ovarian cancer could have similar effectiveness compared to standard 15 mg/kg/3week dosing. Increase of OS and PFS in patients treated with primary and secondary debulking surgery with no-visible disease was more pronounced. No new safety information was observed but lower rate of grade 3 or above hypertension with similar rate of severe vascular and intestinal complications were detected.

Low Advanced Lung Cancer Inflammation Index Predicts Poor Prognosis in Locally Advanced Nasopharyngeal Carcinoma Patients Treated with Definitive Concurrent Chemoradiotherapy.

PURPOSE: We aimed to retrospectively investigate the prognostic worth of pretreatment advanced lung cancer inflammation index (ALI) in locally advanced nasopharyngeal carcinoma (LA-NPC) patients treated with concurrent chemoradiotherapy (C-CRT). Patients and Methods. A total of 164 LA-NPC patients treated with cisplatinum-based definitive C-CRT were included in this retrospective cohort analysis. The convenience of ideal pre-C-CRT ALI cut-offs affecting survival results was searched by employing the receiver operating characteristic (ROC) curve analyses. The primary endpoint was the link between the ALI groups and overall survival (OS), while cancer-specific survival (CSS), locoregional progression-free survival [LR(PFS)], distant metastasis-free survival (DMFS), and PFS comprised the secondary endpoints. RESULTS: The ROC curve analyses distinguished a rounded ALI cut-off score of 24.2 that arranged the patients into two cohorts [ALI ≥ 24.2 (N = 94) versus < 24.2 (N = 70)] with significantly distinct CSS, OS, DMFS, and PFS outcomes, except for the LRPFS. At a median follow-up time of 79.2 months (range: 6-141), the comparative analyses showed that ALI < 24.2 cohort had significantly shorter median CSS, OS, DMFS, and PFS time than the ALI ≥ 24.2 cohort (P < 0.001for each), which retained significance at 5- (P < 0.001) and 10-year (P < 0.001) time points. In multivariate analyses, ALI < 24.2 was asserted to be an independent predictor of the worse prognosis for each endpoint (P < 0.001for each) in addition to the tumor stage (T-stage) (P < 0.05 for all endpoints) and nodal stage (N-stage) (P < 0.05 for all endpoints). CONCLUSION: As a novel prognostic index, the pretreatment ALI < 24.2 appeared to be strongly associated with significantly diminished survival outcomes in LA-NPC patients treated with C-CRT independent of the universally recognized T- and N-stages.

Comparison of Involved Field Radiotherapy versus Elective Nodal Irradiation in Stage IIIB/C Non-Small-Cell Lung Carcinoma Patients Treated with Concurrent Chemoradiotherapy: A Propensity Score Matching Study.

BACKGROUND: We retrospectively compared the incidence of isolated elective nodal failure (IENF) and toxicity rates and survival outcomes after elective nodal irradiation (ENI) versus involved-field RT (IFRT) by employing the propensity score matching (PSM) methodology in stage IIIB/C inoperable non-small-cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). METHODS: Our PSM examination included 1048 stage IIIB/C NSCLC patients treated with C-CRT from January 2007 to December 2016: a total dose of 66 Gy (2 Gy/fraction) radiotherapy and 1-3 cycles of platinum-based doublet chemotherapy concurrently. The primary and secondary endpoints were the IENF and toxicity rates and survival outcomes after ENI versus IFRT, respectively. Propensity scores were calculated for each group to adjust for confounding variables and facilitate well-balanced comparability by creating 1 : 1 matched study groups. RESULTS: The median follow-up was 26.4 months for the whole study accomplice. The PSM analysis unveiled 1 : 1 matched 646 patients for the ENI (N = 323) and IFRT (N = 323) cohorts. Intergroup comparisons discovered that the 5-year isolated ENF incidence rates (3.4% versus 4.3%; P=0.52) and median overall survival (25.2 versus 24.6 months; P=0.69), locoregional progression-free survival (15.3 versus 15.1 months; P=0.52), and progression-free survival (11.7 versus 11.2 months; P=0.57) durations were similar between the ENI and IFRT cohorts, separately. However, acute grade 3-4 leukopenia (P=0.0012), grade 3 nausea-vomiting (P=0.006), esophagitis (P=0.003), pneumonitis (P=0.002), late grade 3-4 esophageal toxicity (P=0.038), and the need for hospitalization (P < 0.001) were all significantly higher in the ENI than in the IFRT group, respectively. CONCLUSION: Results of the present large-scale PSM cohort established the absence of meaningful IENF or survival differences between the IFRT and ENI cohorts and, consequently, counseled the IFRT as the elected RT technique for such patients since ENI increased the toxicity rates.

Low Systemic Inflammation Response Index Predicts Good Prognosis in Locally Advanced Pancreatic Carcinoma Patients Treated with Concurrent Chemoradiotherapy.

BACKGROUND: We investigated the prognostic significance of pretreatment systemic inflammation response index (SIRI) in locally advanced pancreatic carcinoma (LAPC) patients treated with concurrent chemoradiotherapy (CRT). METHODS: Present retrospective cohort analysis investigated consecutive 154 LAPC patients who received radical CRT. The SIRI was defined as: SIRI = neutrophil × monocyte/lymphocyte counts. Ideal SIRI cutoff(s) influencing overall survival (OS) and progression-free survival (PFS) results were sought by using receiver operating characteristic (ROC) curve analysis. The primary endpoint was the interaction between the SIRI and OS results. RESULTS: The median follow-up, PFS, and OS durations were 14.3 (range: 2.9-74.6), 7.9 [%95 confidence interval (CI): 5.7-10.1), and 14.7 months (%95 CI: 11.4-18.0) for the entire cohort, respectively. ROC curve analyses determined the ideal SIRI cutoff that exhibiting a significant link with OS and PFS outcomes at the rounded 1.6 point (AUC: 74.3%; sensitivity: 73.8%; specificity: 70.1%).The SIRI <1.6 patients (N = 58) had significantly superior median PFS (13.8 versus 6.7 months; P < 0.001) and OS (28.6 versus 12.6 months; P < 0.001) lengths than SIRI ≥1.6 patients (N = 96), respectively. Although the N0 (versus N1; P < 0.05) and CA 19-9 ≤90 U/mL (versus >90 U/mL) appeared as the other significant associates of better OS and PFS in univariate analyses, yet the results of multivariate analyses confirmed the SIRI <1.6 as the independent indicator of superior OS and PFS (P < 0.001 for each). CONCLUSION: Pretreatment SIRI is a novel independent prognosticator that may further enhance the conventional tumor-node-metastases staging system in a more precise prediction of the OS and PFS outcomes of LAPC patients after radical CRT.