Comparison of outcomes between early-stage cervical cancer patients without high-risk factors undergoing adjuvant concurrent chemoradiotherapy and radiotherapy alone after radical surgery.

PURPOSE: For patients with early-stage cervical cancer without high-risk factors, there is no consensus regarding the optimal postoperative treatment regimen and whether postoperative concurrent radiochemotherapy (CCRT) is superior to radiotherapy (RT) alone. PATIENTS AND METHODS: The medical records of patients with stage I-IIA cervical cancer, who underwent radical surgery and postoperative RT or CCRT between June 2012 and December 2017, were retrospectively reviewed. Patients with any high-risk factors, including positive pelvic lymph node(s), positive resection margin(s), and parametrial invasion, were excluded. Patients with large tumors (≥ 4 cm), deep stromal invasion (≥ 1/2), and lymphovascular space involvement were categorized as the intermediate-risk group. Patients without intermediate-risk factors were categorized as the low-risk group. RESULTS: A total of 403 patients were enrolled and divided into 2 groups according to postoperative treatment: RT alone (n = 105); and CCRT (n = 298). For risk stratification, patients were also divided into 2 groups: intermediate-risk (n = 350); and low-risk (n = 53). The median follow-up was 51.7 months. Patients in the intermediate-risk group and those with multiple intermediate-risk factors were more likely to undergo CCRT. For patients who underwent RT alone or CCRT in the intermediate-risk group, 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), and 5-year disease-free survival (DFS) rates were 90.6% and 91.4%, respectively (p = 0.733). Similarly, for patients who underwent RT alone or CCRT in the low-risk group, the 5-year OS rates were 100.0% and 93.5% (p = 0.241), and 5-year DFS rates were 94.4% and 93.5%, respectively (p = 0.736). Adjuvant CCRT or RT were not independent risk factors for either OS or DFS. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those in the RT group (44.0% versus 11.4%, respectively; p < 0.001). There was no significant difference in grade ≥ 3 chronic toxicities of the urogenital and gastrointestinal systems between the CCRT and RT groups. CONCLUSION: There was no significant difference in 5-year OS and DFS rates between patients with early-stage cervical cancer without high-risk factors undergoing postoperative CCRT versus RT alone. Patients who underwent CCRT appeared to develop a higher proportion of grade ≥ 3 acute hematological toxicities than those who underwent RT alone.

Anti-epileptic drug use during adjuvant chemo-radiotherapy is associated with poorer survival in patients with glioblastoma: A nationwide population-based cohort study.

INTRODUCTION: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome. MATERIAL AND METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862). CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.

Influence of neoadjuvant treatment strategy on perioperative outcomes in locally advanced rectal cancer.

AIM: Neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer facilitates tumour downstaging and complete pathological response (pCR). The goal of neoadjuvant systemic chemotherapy (total neoadjuvant chemotherapy, TNT) is to further improve local and systemic control. While some patients forgo surgery, total mesorectal excision (TME) remains the standard of care. While TNT appears to be noninferior to nCRT with respect to short-term oncological outcomes few data exist on perioperative outcomes. Perioperative morbidity including anastomotic leaks is associated with a negative effect on oncological outcomes, probably due to a delay in proceeding to adjuvant therapy. Thus, we aimed to compare conversion rates, rates of sphincter-preserving surgery and anastomosis formation rates in patients undergoing rectal resection after either TNT or standard nCRT. METHODS: An institutional colorectal oncology database was searched from January 2018 to July 2023. Inclusion criteria comprised patients with histologically confirmed rectal cancer who had undergone neoadjuvant therapy and TME. Exclusion criteria comprised patients with a noncolorectal primary, those operated on emergently or who had local excision only. Outcomes evaluated included rates of conversion to open, sphincter-preserving surgery, anastomosis formation and anastomotic leak. RESULTS: A total of 119 patients were eligible for inclusion (60 with standard nCRT, 59 with TNT). There were no differences in rates of sphincter preservation or primary anastomosis formation between the groups. However, a significant increase in conversion to open (p = 0.03) and anastomotic leak (p = 0.03) was observed in the TNT cohort. CONCLUSION: In this series TNT appears to be associated with higher rates of conversion to open surgery and higher anastomotic leak rates. While larger studies will be required to confirm these findings, these factors should be considered alongside oncological benefits when selecting treatment strategies.

Risk Factors for Distant Metastasis in Extrahepatic Bile Duct Cancer after Curative Resection (KROG 1814).

PURPOSE: Risk factors predicting distant metastasis (DM) in extrahepatic bile duct cancer (EHBDC) patients treated with curative resection were investigated. MATERIALS AND METHODS: Medical records of 1,418 EHBDC patients undergoing curative resection between Jan 2000 and Dec 2015 from 14 institutions were reviewed. After resection, 924 patients (67.6%) were surveilled without adjuvant therapy, 297 (21.7%) were treated with concurrent chemoradiotherapy (CCRT) and 148 (10.8%) with CCRT followed by chemotherapy. To exclude the treatment effect from innate confounders, patients not treated with adjuvant therapy were evaluated. RESULTS: After a median follow-up of 36.7 months (range, 2.7 to 213.2 months), the 5-year distant metastasis-free survival (DMFS) rate was 57.7%. On multivariate analysis, perihilar or diffuse tumor (hazard ratio [HR], 1.391; p=0.004), poorly differentiated histology (HR, 2.014; p < 0.001), presence of perineural invasion (HR, 1.768; p < 0.001), positive nodal metastasis (HR, 2.670; p < 0.001) and preoperative carbohydrate antigen (CA) 19-9 ≥ 37 U/mL (HR, 1.353; p < 0.001) were significantly associated with inferior DMFS. The DMFS rates significantly differed according to the number of these risk factors. For validation, patients who underwent adjuvant therapy were evaluated. In patients with ≥ 3 factors, additional chemotherapy after CCRT resulted in a superior DMFS compared with CCRT alone (5-year rate, 47.6% vs. 27.7%; p=0.001), but the benefit of additional chemotherapy was not observed in patients with 0-2 risk factors. CONCLUSION: Tumor location, histologic differentiation, perineural invasion, lymph node metastasis, and preoperative CA 19-9 level predicted DM risk in resected EHBDC. These risk factors might help identifying a subset of patients who could benefit from additional chemotherapy after resection.

Long-Term Total Neoadjuvant Therapy Leads to Impressive Response Rates in Rectal Cancer: Results of a German Single-Center Cohort.

Intensified preoperative chemotherapy after (chemo)radiotherapy, (Total Neoadjuvant Therapy-TNT), increases pathological complete response (pCR) rates and local control. In cases of clinically complete response (cCR) and close follow-up, non-operative management (NOM) is feasible. We report early outcomes and toxicities of a long-term TNT regime in a single-center cohort. Fifteen consecutive patients with distal or middle-third locally advanced rectal cancer (UICC stage II-III) were investigated, who received neoadjuvant chemoradiotherapy (total adsorbed dose: 50.4 Gy in 28 fractions and two concomitant courses 5-fluorouracil (250 mg/m2/d)/oxaliplatin (50 mg/m2), followed by consolidating chemotherapy (nine courses of FOLFOX4). NOM was offered if staging revealed cCR 2 months after TNT, with resection performed otherwise. The primary endpoint was complete response (pCR + cCR). Treatment-related side effects were quantified for up two years after TNT. Ten patients achieved cCR, of whom five opted for NOM. Ten patients (five cCR and five non-cCR) underwent surgery, with pCR confirmed in the five patients with cCR. The main toxicities comprised leukocytopenia (13/15), fatigue (12/15) and polyneuropathy (11/15). The most relevant CTC °III + IV events were leukocytopenia (4/15), neutropenia (2/15) and diarrhea (1/15). The long-term TNT regime resulted in promising response rates that are higher than the response rates of short TNT regimes. Overall tolerability and toxicity were comparable with the results of prospective trials.

Adjuvant chemotherapy does not improve cancer-specific survival for pathologic stage II/III rectal adenocarcinoma after neoadjuvant chemoradiotherapy and surgery: evidence based on long-term survival analysis from SEER data.

PURPOSE: Adjuvant chemotherapy is controversial in rectal cancer, especially after neoadjuvant chemoradiotherapy (NCRT). This retrospective study aims at evaluating adjuvant chemotherapy's long-term survival benefits in stage II and stage III rectal adenocarcinoma (RC). METHODS: This study obtained data from the Surveillance, Epidemiology, and End Results (SEER) database registered between 2010 and 2015. The survival analyses used the Kaplan-Meier method and were compared by log-rank test. The factors that affect survival outcomes were analyzed by univariate and multivariate Cox regression. The propensity score matching (1:4) was used to ensure the balance of variables between different groups. RESULTS: The median follow-up time for overall patients was 64 months. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates were 51.3% and 67.4% in the adjuvant chemotherapy (-) group and 73.9% and 79.6% in the adjuvant chemotherapy ( +) group (p < 0.001, p = 0.002). However, subgroup analysis showed adjuvant chemotherapy after NCRT improved the 5-year OS but not CSS rates in stage II and stage III RC (p = 0.003, p = 0.004; p = 0.29, p = 0.3). Univariate and multivariate analyses found adjuvant chemotherapy after NCRT was an independent prognosis factor of OS but not CSS (HR 0.8, 95%CI 0.7-0.92, p < 0.001; p = 0.276). CONCLUSION: The survival benefits from adjuvant chemotherapy were associated with the status of NCRT for pathological stage II and III RC. For patients who did not receive NCRT, adjuvant chemotherapy is needed to significantly improve long-term survival rates. However, adjuvant chemotherapy after NCRT did not significantly improve long-term CSS.

Long-Term Toxic Effects, Swallow Function, and Quality of Life on MC1273: A Phase 2 Study of Dose De-escalation for Adjuvant Chemoradiation in Human Papillomavirus-Positive Oropharyngeal Cancer.

PURPOSE: Patients with human papillomavirus oropharyngeal cancer are highly curable but risk significant long-term toxic effects with standard therapy. This study investigated a de-escalation strategy of decreased adjuvant radiation therapy and chemotherapy after transoral robotic surgery, and reports on long-term functional and quality of life (QOL) outcomes. METHODS AND MATERIALS: Eligible patients had a p16-positive oropharyngeal cancer and ≤10 pack-year smoking history and underwent surgery followed by treatment with either 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks with weekly docetaxel (15 mg/m2) if they had intermediate pathologic risk factors or 36 Gy in 1.8-Gy fractions twice per day over 2 weeks with the same chemotherapy if they had extranodal extension. Toxic effects, swallow function, and QOL were measured longitudinally. RESULTS: Seventy-nine patients (89.9% male) were treated and eligible for toxic effect and functional evaluation. Dry mouth was the most common grade 1 toxic effect at 1 year (55.6%), 2 years (53.3%), and 3 years (49.2%). The cumulative rates of grade 2 toxic effects at 1, 2, and 3 years were 1.4%, 6.7%, and 6.8%, respectively. There were only 2 grade 3 toxic effects at ≥1 year, including a grade 3 fatigue at 2.5 years, and a grade 3 superficial soft tissue fibrosis at 4 years. There were no grade 4 to 5 toxic effects. No patients were percutaneous endoscopic gastrostomy-dependent. Swallow function improved by 12 months posttreatment. QOL improved over time by all measurement tools and most patients returned to baseline level of function and QOL. CONCLUSIONS: De-escalated adjuvant therapy for select patients with human papillomavirus oropharyngeal cancer resulted in low rates of long-term toxic effects, excellent swallow outcomes, and preservation of global and xerostomia-related QOL.

Development and validation of a 6-gene signature for the prognosis of loco-regional control in patients with HPV-negative locally advanced HNSCC treated by postoperative radio(chemo)therapy.

PURPOSE: The aim of this study was to develop and validate a novel gene signature from full-transcriptome data using machine-learning approaches to predict loco-regional control (LRC) of patients with human papilloma virus (HPV)-negative locally advanced head and neck squamous cell carcinoma (HNSCC), who received postoperative radio(chemo)therapy (PORT-C). MATERIALS AND METHODS: Gene expression analysis was performed using Affymetrix GeneChip Human Transcriptome Array 2.0 on a multicentre retrospective training cohort of 128 patients and an independent validation cohort of 114 patients from the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG). Genes were filtered based on differential gene expression analyses and Cox regression. The identified gene signature was combined with clinical parameters and with previously identified genes related to stem cells and hypoxia. Technical validation was performed using nanoString technology. RESULTS: We identified a 6-gene signature consisting of four individual genes CAV1, GPX8, IGLV3-25, TGFBI, and one metagene combining the highly correlated genes INHBA and SERPINE1. This signature was prognostic for LRC on the training data (ci = 0.84) and in validation (ci = 0.63) with a significant patient stratification into two risk groups (p = 0.005). Combining the 6-gene signature with the clinical parameters T stage and tumour localisation as well as the cancer stem cell marker CD44 and the 15-gene hypoxia-associated signature improved the validation performance (ci = 0.69, p = 0.001). CONCLUSION: We have developed and validated a novel prognostic 6-gene signature for LRC of HNSCC patients with HPV-negative tumours treated by PORT-C. After successful prospective validation the signature can be part of clinical trials on the individualization of radiotherapy.

Chemotherapy versus chemoradiotherapy for FIGO stages IB1 and IIA1 cervical squamous cancer patients with lymphovascular space invasion: a retrospective study.

PURPOSE: To evaluate the impact of different adjuvant therapy on IB1 and IIA1 stage cervical squamous cell cancer patients with lymphovascular space invasion. It also aimed to analyze the relationship between lymphovascular space invasion and other clinical pathological characteristics on IB1 and IIA1 stage cervical squamous cell cancer patients. METHODS: This retrospective observational study collected data of FIGO stages IB1 and IIA1 squamous cervical cancer patients at the First Affiliated Hospital of Chongqing Medical University between 2014 and 2018. A correlation analysis between lymphovascular space invasion and other clinical or pathological factors was conducted. Prognosis analysis of patients with lymphovascular space invasion were performed to assess associations between clinical-pathological characteristics and survival. RESULTS: A total of 357 women were identified including 110 (30.8%) with lymphovascular space invasion, 247 (69.2%) without lymphovascular space invasion. Both middle 1/3 cervical stromal invasion (p = 0.000) and deep 1/3 cervical stromal invasion (p = 0.000) were independently associated with lymphovascular space invasion. Among lymphovascular space involved women, tumor differentiation (P = 0.001) and postoperative therapy (P = 0.036) had a significant influence on disease recurrence. Multivariate analysis showed that lymph node metastasis (P = 0.017), poorer tumor differentiation (P = 0.036) and postoperative chemotherapy alone (P = 0.021) can increase the risk of tumor relapse. CONCLUSION: Our study suggested that the presence of deep stromal invasion independently increases the risk of lymphovascular space invasion. Compared with chemotherapy, chemoradiotherapy seems to improve progression-free survival in squamous cervical cancer patients with lymphovascular space invasion.

Preoperative versus postoperative chemo-radiotherapy for locally advanced gastric cancer: a multicenter propensity score-matched analysis.

BACKGROUND: Peri-operative chemo-radiotherapyplayed important rolein locally advanced gastric cancer. Whether preoperative strategy can improve the long-term prognosis compared with postoperative treatment is unclear. The study purpose to compare oncologic outcomes in locally advanced gastric cancer patients treated with preoperative chemo-radiotherapy (pre-CRT) and postoperative chemo-radiotherapy (post-CRT). METHODS: From January 2009 to April 2019, 222 patients from 2 centers with stage T3/4 and/or N positive gastric cancer who received pre-CRT and post-CRT were included. After propensity score matching (PSM), comparisons of local regional control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were performed using Kaplan-Meier analysis and log-rank test between pre- and post-CRT groups. RESULTS: The median follow-up period was 30 months. 120 matched cases were generated for analysis. Three-year LC, DMFS, DFS and OS for pre- vs. post-CRT groups were 93.8% vs. 97.2% (p = 0.244), 78.7% vs. 65.7% (p = 0.017), 74.9% vs. 65.3% (p = 0.042) and 74.4% vs. 61.2% (p = 0.055), respectively. Pre-CRT were significantly associated with DFS in uni- and multi-variate analysis. CONCLUSION: Preoperative CRT showed advantages of oncologic outcome compared with postoperative CRT. TRIAL REGISTRATION: ClinicalTrial.gov NCT01291407 , NCT03427684 and NCT04062058 , date of registration: Feb 8, 2011.

Prognosis of Interval Distant Metastases After Neoadjuvant Chemoradiotherapy for Esophageal Cancer.

BACKGROUND: In esophageal cancer patients, distant metastases develop between the start of neoadjuvant chemoradiotherapy and planned surgery, so-called interval metastases. The primary aim of this study was to assess management, overall survival (OS), and prognostic factors for OS in these patients. A secondary aim was to compare OS with synchronous metastatic patients. METHODS: Esophageal cancer patients with interval distant metastases were identified from the Netherlands Cancer Registry (2010 to 2017). Management was categorized into metastasis-directed therapy (MDT), primary tumor resection, or best supportive care (BSC). The OS was calculated from the diagnosis of the primary tumor. Prognostic factors affecting OS were studied using Cox proportional hazard models. Propensity score-matching (1:3) generated matched cases with synchronous distant metastases. RESULTS: In all, 208 patients with interval metastases were identified: in 87 patients (42%) MDT was initiated; in 10%, primary tumor resection only; in 7%, primary tumor resection plus MDT; and in 41%, BSC. Median OS was 10 months (interquartile range, 8.6 to 11.1). Compared with BSC, superior OS was independently associated with MDT (hazard ratio [HR] 0.36; 95% confidence interval [CI], 0.26 to 0.49), primary tumor resection (HR 0.55; 95% CI, 0.33 to 0.94), and primary tumor resection plus MDT (HR 0.20; 95% CI, 0.10 to 0.38). Worse OS was independently associated with signet ring cell carcinoma (HR 1.92; 95% CI, 1.12 to 3.28) and poor differentiation grade (HR 1.96; 95% CI, 1.35 to 2.83). The OS was comparable between matched patients with interval and synchronous distant metastases (10.2 versus 9.4 months, P = .760). CONCLUSIONS: In esophageal cancer patients treated with neoadjuvant chemoradiotherapy with interval distant metastases, the OS was poor and comparable to that of synchronous metastatic patients.

Impact of Dose-Escalated Chemoradiation on Quality of Life in Patients With Locally Advanced Rectal Cancer: 2-Year Follow-Up of the Randomized RECTAL-BOOST Trial.

PURPOSE: Dose-escalated chemoradiation (CRT) for locally advanced rectal cancer did not result in higher complete response rates but initiated more tumor regression in the randomized RECTAL-BOOST trial (Clinicaltrials.gov NCT01951521). This study compared patient reported outcomes between patients who received dose-escalated CRT (5 × 3 gray boost + CRT) or standard CRT for 2 years after randomization. METHODS AND MATERIALS: Patients with locally advanced rectal cancer who were participating in the RECTAL-BOOST trial filled out European Organisation for Research and Treatment of Cancer QLQ-C30 and CR29 questionnaires on quality of life (QoL) and symptoms at baseline, 3, 6, 12, 18, and 24 months after start of treatment. Between-group differences in functional QoL domains were estimated using a linear mixed-effects model and expressed as effect size (ES). Symptom scores were compared using Mann-Whitney U test. RESULTS: Patients treated with dose-escalated CRT (boost group, n = 51) experienced a significantly stronger decline in global health at 3 and 6 months (ES -0.4 and ES -0.4), physical functioning at 6 months (ES -1.1), role functioning at 3 and 6 months (ES -0.8 and ES -0.6), and social functioning at 6 months (ES -0.6), compared with patients treated with standard CRT (control group, n = 64). The boost group reported significantly more fatigue at 3 and 6 months (83% vs 66% respectively 89% vs 76%), pain at 3 and 6 months (67% vs 36% respectively 80% vs 44%), and diarrhea at 3 months (45% vs 29%) compared with the control group. From 12 months onwards, QoL and symptoms were similar between groups, apart from more blood/mucus in stool in the boost group. CONCLUSIONS: In patients with locally advanced rectal cancer, dose-escalated CRT resulted in a transient deterioration in global health, physical, role, and social functioning and more pain, fatigue and diarrhea at 3 and 6 months after start of treatment compared with standard CRT. From 12 months onwards, the effect of dose-escalated CRT on QoL largely resolved.

Analysis of Post-operative Adjuvant Chemotherapy Versus Adjuvant Chemoradiation Therapy Outcomes in Non-metastatic Cholangiocarcinoma: an NCDB Review.

BACKGROUND: Each year, approximately 8000 cases of cholangiocarcinoma are recorded in the USA. Surgical resection is considered to be the only curative option. Despite surgery as a curative approach, many patients will require adjuvant therapies in the form of chemotherapy (ChT) or chemoradiotherapy (CRT). As such, we sought to analyze outcomes in patients with non-metastatic cholangiocarcinoma receiving adjuvant ChT or CRT following surgical resection. METHODS: We queried the National Cancer Database (NCDB) for patients with a diagnosis of non-metastatic cholangiocarcinoma between the years 2010 and 2015 who underwent adjuvant ChT or CRT following surgery. Overall survival (OS) was calculated using Kaplan Meier method. Cox proportional hazard ratios were used to identify predictors of overall survival, and logistic regression was used to identify predictors of receiving each treatment. RESULTS: A total of 875 patients were identified who met the above eligibility criteria. Of these patients, 818 received adjuvant chemotherapy alone with 57 patients receiving adjuvant chemoradiation therapy. The median OS in patients receiving CRT was 19.8 months versus 11.9 months for ChT (p value < 0.0238). The 1- and 5-year survival rates between ChT and CRT were 50% vs 61% and 6% vs 13%, respectively (hazard ratio 0.7005; 95% CI 0.51-0.97; p value < 0.0294). CONCLUSION: The results of this study suggest a potential benefit of chemoradiation therapy in the adjuvant setting, although the trends appear to show rare utilization. Given the limitations of our study, prospective corroboration is warranted.

Initial treatment and survival in Danish patients diagnosed with non-small-cell lung cancer (2005-2015): SCAN-LEAF study.

Aim: To describe initial treatment patterns and survival of patients diagnosed with non-small-cell lung cancer (NSCLC) in Denmark, before immune checkpoint inhibitor and later-generation tyrosine kinase inhibitor use. Patients & methods: Adults diagnosed with incident NSCLC (2005-2015; follow-up: 2016). Initial treatments and overall survival (OS) are reported. Results: 31,939 NSCLC patients (51.6% stage IV) were included. Increasing use of curative radiotherapy/chemoradiation for stage I, II/IIIA and IIIB NSCLC coincided with improved 2-year OS. Systemic anticancer therapy use increased for patients with stage IV non-squamous NSCLC (53.0-60.6%) but not squamous NSCLC (44.9-47.3%). 1-year OS improved in patients with stage IV non-squamous NSCLC (23-31%) but not squamous NSCLC (22-25%). Conclusion: Trends indicated improved OS as treatments evolved between 2005 and 2015, but the effect was limited to 1-year OS in stage IV disease.

Overall survival benefit of osimertinib and clinical value of upfront cranial local therapy in untreated EGFR-mutant nonsmall cell lung cancer with brain metastasis.

Osimertinib, as a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), showed more potent efficacy against brain metastasis (BM) in untreated EGFR-mutant nonsmall cell lung cancer (NSCLC) in the FLAURA study. However, the overall survival (OS) benefit of osimertinib and clinical value of cranial local therapy (CLT) in these patients remain undetermined. Here we conducted a retrospective study involving untreated EGFR-mutant NSCLC patients with BMs receiving first-line osimertinib or first-generation EGFR-TKIs. Upfront CLT was defined as CLT performed before disease progression to the first-line EGFR-TKIs. Pattern of treatment failure and survival outcomes were extensively investigated. Among the 367 patients enrolled, first-generation EGFR-TKI was administered in 265, osimertinib in 102 and upfront CLT performed in 140. Patients receiving osimertinib had more (P < .001) and larger BMs (P = .003) than those receiving first-generation EGFR-TKIs. After propensity score matching, osimertinib was found to prolong OS (37.7 vs 22.2 months, P = .027). Pattern of failure analyses found that 51.8% of the patients without upfront CLT developed their initial progressive disease (PD) in the brain and 59.0% of the cranial PD occurred at the original sites alone, suggesting potential clinical value of upfront CLT. Indeed, upfront stereotactic radiosurgery (SRS) and/or surgery was associated with improved OS among those receiving first-generation EGFR-TKIs (P = .019) and those receiving osimertinib (P = .041). In summary, compared to first-generation EGFR-TKIs, osimertinib is associated with improved OS in untreated EGFR-mutant NSCLC with BMs. Meanwhile, upfront SRS and/or surgery may provide extra survival benefit, which needs to be verified in future studies.

Cervical cancer treatment in Rwanda: Resource-driven adaptations, quality indicators, and patient outcomes.

OBJECTIVE: Most cervical cancer cases and deaths occur in low- and middle-income countries, yet clinical research from these contexts is significantly underrepresented. We aimed to describe the treatment quality, resource-driven adaptations, and outcomes of cervical cancer patients in Rwanda. METHODS: A retrospective cohort study was conducted of all patients with newly diagnosed cervical cancer enrolled between April 2016 and June 2018. Data were abstracted from medical records and analyzed using descriptive statistics, Kaplan Meier methods, and Cox proportional hazards regression. RESULTS: A total of 379 patients were included; median age 54 years, 21% HIV-infected. A majority (55%) had stage III or IV disease. Thirty-four early-stage patients underwent radical hysterectomy. Of 254 patients added to a waiting list for chemoradiation, 114 ultimately received chemoradiation. Of these, 30 (26%) received upfront chemoradiation after median 126 days from diagnosis, and 83 (73%) received carboplatin/paclitaxel while waiting, with a median 56 days from diagnosis to chemotherapy and 207 days to chemoradiation. There was no survival difference between the upfront chemoradiation and prior chemotherapy subgroups. Most chemotherapy recipients (77%) reported improvement in symptoms. Three-year event-free survival was 90% with radical hysterectomy (95% CI 72-97%), 66% with chemoradiation (95% CI 55-75%), and 12% with chemotherapy only (95% CI 6-20%). CONCLUSIONS: Multi-modality treatment of cervical cancer is effective in low resource settings through coordinated care and pragmatic approaches. Our data support a role for temporizing chemotherapy if delays to chemoradiation are anticipated. Sustainable access to gynecologic oncology surgery and expanded access to radiotherapy are urgently needed.

Physical activity programmes for patients undergoing neo-adjuvant chemoradiotherapy for rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Patients diagnosed with localized rectal cancer should undergo Neoadjuvant Radio-Chemotherapy (NACRT) followed, a few weeks later, by surgical resection. NACRT is known to cause significant decline in the physical and psychological health of patients. This literature review aims to summarize the effects of a prehabilitation programme during and/or after NACRT but before surgery. METHODS: Articles included in this review have been selected by two independent researchers on Pubmed, Google Scholar, and Cochrane databases with the following terms: "Rectal Cancer AND Physical Activity" and "Exercise AND Rectal Cancer." RESULTS: We obtained 560 articles. We selected 12 of these, representing 7 series but only one randomized study, constituting 153 patients in total. Most studies included have considerable variation in their prehabilitation programmes, in terms of supervision, training content, frequency, intensity, duration, and temporality, in regard to NACRT and surgery. Implementing a prehabilitation programme during NACRT seems feasible and safe, with adherence ranging from 58% to 100%. VO2max (maximal oxygen consumption during incremental exercise) was improved in three of the studies during the prehabilitation programme. No significant difference in the step count, 6-minute-walk test, or quality of life was seen. CONCLUSIONS: Prehabilitation programmes during NACRT for localized rectal cancer patients are safe and feasible; however, due to considerable variation in the prehabilitation programmes and their small size, impact on fitness, quality of life, and surgical outcome are unknown. Larger randomized studies are needed.

Strategies to Improve the Antitumor Effect of Immunotherapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC), one of the most fatal malignancies in the world, is usually diagnosed in advanced stages due to late symptom manifestation with very limited therapeutic options, which leads to ineffective intervention and dismal prognosis. For a decade, tyrosine kinase inhibitors (TKIs) have offered an overall survival (OS) benefit when used in a first-line (sorafenib and lenvatinib) and second-line setting (regorafenib and cabozantinib) in advanced HCC, while long-term response remains unsatisfactory due to the onset of primary or acquired resistance. Recently, immunotherapy has emerged as a promising therapy in the treatment of several solid tumors, such as melanoma and non-small cell lung cancer. Moreover, as the occurrence of HCC is associated with immune tolerance and immunosurveillance escape, there is a potent rationale for employing immunotherapy in HCC. However, immunotherapy monotherapy, mainly including immune checkpoint inhibitors (ICIs) that target checkpoints programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and the cytotoxic T lymphocyte antigen-4 (CTLA-4), has a relatively low response rate. Thus, the multi-ICIs or the combination of immunotherapy with other therapies, like antiangiogenic drugs and locoregional therapies, has become a novel strategy to treat HCC. Combining different ICIs may have a synergistical effect attributed to the complementary effects of the two immune checkpoint pathways (CTLA-4 and PD-1/PD-L1 pathways). The incorporation of antiangiogenic drugs in ICIs can enhance antitumor immune responses via synergistically regulating the vasculature and the immune microenvironment of tumor. In addition, locoregional treatments can improve antitumor immunity by releasing the neoplasm antigens from killed tumor cells; in turn, this antitumor immune response can be intensified by immunotherapy. Therefore, the combination of locoregional treatments and immunotherapy may achieve greater efficacy through further synergistic effects for advanced HCC. This review aims to summarize the currently reported results and ongoing trials of the ICIs-based combination therapies for HCC to explore the rational combination strategies and further improve the survival of patients with HCC.

Omitting surgery in esophageal cancer patients with complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a standard treatment modality for locally-advanced esophageal cancer. However, patients who achieve clinical complete response (cCR) after nCRT have been reported to have better prognosis. Further, the role of surgery in these patients is controversial. Thus, this meta-analysis aimed to evaluate whether surgery is still useful in patients with cCR after nCRT. METHODS: We systematically reviewed the MEDLINE, PubMed, Embase, Cochrane library, and Scopus databases for studies on surgical efficacy in complete responders after concurrent chemoradiotherapy for esophageal cancer. The publication date was set to January 1, 2010-January 31, 2020. The hazard ratio (HR) and risk ratio were used to compare the 2-year overall survival (OS), disease-free survival (DFS), incidence of locoregional failure, distant metastasis, and treatment mortality between the nCRT and nCRT plus surgery groups. RESULTS: Six articles involving 609 patients were included. There was a significant benefit of nCRT for OS (HR = 0.80, 95% confidence interval [CI] 0.64-0.99, p = 0.04), but not for DFS (HR = 1.55, 95% CI 0.35-6.86, p = 0.56). The nCRT group tended to have lower mortality than the nCRT plus surgery group (risk ratio = 0.15, 95% CI 0.02-1.18, p = 0.07). CONCLUSION: Omitting surgery provides better OS in complete responders after nCRT. Adding surgery could increase the morbidity and mortality and decrease the quality of life. Thus, nCRT alone could be a feasible approach for patients with cCR.

Patterns and timing of recurrence in esophageal squamous cell carcinoma patients treated with neoadjuvant chemoradiotherapy plus esophagectomy.

BACKGROUND: Tumor regression grade (TRG) after neoadjuvant therapy is reportedly predictive of prognosis in esophageal cancer patients, as lack of a response to neoadjuvant therapy is associated with a poor prognosis. However, there is little information available on the timing and pattern of recurrence after esophagectomy for thoracic esophageal squamous cell carcinoma (TESCC) that takes into consideration TRG after neoadjuvant chemoradiotherapy (NACRT). Here, in an effort to gain insight into a treatment strategy that improves the prognosis of NACRT non-responders, we evaluated the patterns and timing of recurrence in TESCC patients, taking into consideration TRG after NACRT. METHODS: A total of 127 TESCC patients treated with NACRT and esophagectomy between 2009 and 2017 were enrolled in this observational cohort study. TRGs were assigned based on the proportion of residual tumor cells in the area (TRG1, ≥1/3 viable cancer cells; 2, < 1/3 viable cancer cells; 3, no viable cancer cells). We retrospectively investigated the timing and patterns of recurrence and the prognoses in TESCC patients, taking into consideration TRG after NACRT. RESULTS: The 127 participating TESCC patients were categorized as TRG1 (42 patients, 33%), TRG2 (56 patients, 44%) or TRG3 (29 patients, 23%). The locoregional recurrence rate was higher in TRG1 (36.4%) patients than combined TRG2-3 (7.4%) patients. Patients with TRG3 had better prognoses, though a few TRG3 patients experienced distant recurrence. There were no significant differences in median time to first recurrence or OS among patients with locoregional or distant recurrence. There was a trend toward better OS in TRG2-3 patients with recurrence than TRG1 patients with recurrence, but the difference was not significant. CONCLUSIONS: NACRT non-responders (TRG1 patients) experienced higher locoregional recurrence rates and earlier recurrence with distant or locoregional metastasis. TRG appears to be useful for establishing a strategy for perioperative treatments to improve TESCC patient survival, especially among TRG1 patients. (303 words).