Concurrent Chemoradiotherapy Research Articles

A new treatment approach of toripalimab in combination with concurrent platinum-based chemoradiotherapy for locally advanced cervical cancer: A phase II clinical trial.

This study investigated the efficacy and safety of toripalimab in combination with concurrent platinum-based chemoradiation in patients with untreated locally advanced cervical cancer. Eligible patients received toripalimab 240 mg once every 3 weeks in combination with concurrent platinum-based chemoradiotherapy, followed by the maintenance of toripalimab once every 6 weeks up to 1 year. The primary endpoint was objective response rate (ORR). Secondary endpoints included 2-year and 3-year progression-free survival (PFS) rates, 3-year overall survival (OS) rate, and safety. Biomarker analysis of PD-L1 expression and genomic mutational analysis by next-generation sequencing were conducted, as well as PD-L1 expression on tumor biopsies. A total of 82 patients were enrolled. The median follow-up was 21 months (range, 5.2-44.5 months). The ORR and disease control rate were both 87.8% among the 82 patients. Median PFS and OS were not reached. A trend toward longer PFS was observed in the populations with a PD-L1 combined positive score ≥10, low tumor mutation burden and loss of heterozygosity in human leukocyte antigen (HLA LOH) detected populations. A total of 37 patients experienced treatment-related adverse events, of which 17 (20.7%) patients experienced grade 3 or higher adverse events. Collectively, toripalimab plus concurrent platinum-based chemoradiotherapy showed promising antitumor efficacy with acceptable safety profiles in patients with untreated locally advanced cervical cancer.

Prospective longitudinal analysis of imaging-based spatiotemporal tumor habitats in glioblastoma, IDH-wild type: implication in patient outcome using multiparametric physiologic MRI

BackgroundPhysiologic MRI-based tumor habitat analysis has the potential to predict patient outcomes by identifying the spatiotemporal habitats of glioblastoma. This study aims to prospectively validate the cut-off for tumor progression obtained from tumor habitat analysis based on physiologic MRI in ascertaining time-to-progression (TTP) and the site of progression in glioblastoma patients following concurrent chemoradiotherapy (CCRT).MethodsIn this prospective study (ClinicalTrials.gov ID: NCT02613988), we will recruit patients with IDH-wild type glioblastoma who underwent CCRT and obtained immediate post-operative and three serial post-CCRT MRI scans within a three-month interval, conducted using diffusion-weighted imaging and dynamic susceptibility contrast imaging. Voxels from cerebral blood volume and apparent diffusion coefficient maps will be grouped using k-means clustering into three spatial habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue). The spatiotemporal habitats of the tumor will be evaluated by comparing changes in each habitat between the serial MRI scans (post-operative and post-CCRT #1, #2, and #3). Associations between spatiotemporal habitats and TTP will be analyzed using cox proportional hazard modeling. The site of progression will be matched with spatiotemporal habitats.DiscussionThe perfusion- and diffusion-derived tumor habitat in glioblastoma is expected to stratify TTP and may serve as an early predictor for tumor progression in patients with IDH wild-type glioblastoma.Trial registrationClinicalTrials.gov ID: NCT02613988.

Concurrent Chemoradiation ± Atezolizumab (atezo) in Limited-Stage Small Cell Lung Cancer (LS-SCLC): Results of NRG Oncology/Alliance LU005

Concurrent Chemoradiation ± Atezolizumab (atezo) in Limited-Stage Small Cell Lung Cancer (LS-SCLC): Results of NRG Oncology/Alliance LU005

Identifying timing and risk factors for early recurrence of resectable rectal cancer: A single center retrospective study.

Colorectal cancer is a common malignancy and various methods have been introduced to decrease the possibility of recurrence. Early recurrence (ER) is related to worse prognosis. To date, few observational studies have reported on the analysis of rectal cancer. Hence, we reported on the timing and risk factors for the ER of resectable rectal cancer at our institute. To analyze a cohort of patients with local and/or distant recurrence following the radical resection of the primary tumor. Data were retrospectively collected from the institutional database from March 2011 to January 2021. Clinicopathological data at diagnosis, perioperative and postoperative data, and first recurrence were collected and analyzed. ER was defined via receiver operating characteristic curve. Prognostic factors were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. We included 131 patients. The optimal cut off value of recurrence-free survival (RFS) to differentiate between ER (n = 55, 41.9%) and late recurrence (LR) (n = 76, 58.1%) was 8 mo. The median post-recurrence survival (PRS) of ER and LR was 1.4 mo and 2.9 mo, respectively (P = 0.008) but PRS was not strongly associated with RFS (R² = 0.04). Risk factors included age ≥ 70 years [hazard ratio (HR) = 1.752, P = 0.047], preoperative concurrent chemoradiotherapy (HR = 3.683, P < 0.001), colostomy creation (HR = 2.221, P = 0.036), and length of stay > 9 d (HR = 0.441, P = 0.006). RFS of 8 mo was the optimal cut-off value. Although ER was not associated with PRS, it was still related to prognosis; thus, intense surveillance is recommended.

Number of Retrieved Lymph Nodes during Esophagectomy Affects the Outcome of Stage III Esophageal Cancer in Patients Having Had Pre-Operative Chemo-Radiation Therapy.

Background: Lymphadenectomy plays a crucial role in the surgical management of early- stage esophageal cancer. However, few studies have examined lymphadenectomy outcomes in advanced stages, particularly in patients who initially underwent concurrent chemoradiation therapy. This retrospective study investigates the effect of lymphadenectomy in patients diagnosed with AJCC 8th-edition clinical stage III esophageal squamous cell carcinoma who received concurrent preoperative chemoradiation. Methods: Data from 1994 to 2023 were retrieved from our retrospective database. All patients underwent a uniform evaluation and treatment protocol, including preoperative concurrent chemoradiation therapy comprising cisplatin and 5-fluorouracil, followed by esophagectomy. The analysis encompassed clinical T and N stages, tumor location, tumor grade, pathological T and N stages, pathological stage, and the extent of lymph node dissection. Overall survival, "Free-To-Recurrence", and disease-free survival were assessed via Kaplan-Meier survival curves and the Cox regression model for multivariate analysis. Results: The dataset was stratified into two groups according to extent of lymph node dissection, with one group having <15 dissected nodes and the other having ≥15 dissected nodes. The group with <15 nodes exhibited a shorter "Free-To-Recurrence", worse disease-free survival, and lower overall survival. In multiple-variate analysis (Cox regression model), the number of dissected lymph nodes emerged as a significant factor influencing overall survival and freedom from recurrence. Conclusions: The quantity of lymphadenectomy is a crucial determinant for patients with AJCC 8th-edition clinical stage III esophageal squamous cell carcinoma receiving preoperative concurrent chemoradiation.

Unilateral radiotherapy for tonsillar cancer with multiple ipsilateral neck lymph nodes.

For tonsillar cancer with multiple ipsilateral neck lymph nodes, the safety and efficacy of unilateral radiotherapy (RT) have long been a topic of debate. We performed retrospective analyses of patients having ipsilateral neck lymph nodes treated with unilateral RT in two tertiary referral hospitals. This study accrued 29 patients who were diagnosed as well-lateralized tonsillar cancer with multiple ipsilateral neck lymph nodes and underwent unilateral RT from March 2000 to March 2020. Patients underwent treatment with one of the following options or a combination of them: induction chemotherapy, surgery, RT, and concurrent chemoradiotherapy. We analyzed the recurrence pattern and survival with special attention to contralateral neck failure. Also, treatment-related toxicities were compared with a 1:1 matched cohort of those who received bilateral RT, using propensity score matching analysis. At a median follow-up of 68 months, no contralateral neck failure was observed. Five-year actuarial locoregional recurrence-free survival, distant metastasis-free survival, and overall survival were 85.6%, 91.8%, and 92.7%, respectively. Both the acute and chronic grade 2 xerostomia occurred in 10.3% of the patients. When the toxicity for unilateral RT was compared to that of bilateral RT using a propensity score-matched cohort, a significantly lower rate of acute xerostomia was observed in unilateral RT group (55.1% vs. 82.7%, p=0.002), primarily at grade 2 level (10.3% vs. 51.7%, respectively). The results of our study suggest that unilateral RT can be safely performed in well-lateralized tonsillar cancer patients with multiple ipsilateral neck lymph nodes.

Impact of Surveillance Imaging in Patients With HPV-Associated Oropharyngeal Carcinoma Treated With Definitive Radiation and Chemotherapy.

Surveillance imaging for HPV-associated oropharyngeal carcinomas (OPCs) differs among physicians and institutions. Surveillance imaging can detect disease progression earlier, but can also contribute to anxiety and cost, without proven survival benefits. We sought to determine practice patterns of surveillance imaging and the number of surveillance scans needed to detect one recurrence in patients with HPV-associated OPCs. We performed a retrospective cohort study between 2017 and 2019 (median follow-up: 39.9mo) of consecutive patients with locally advanced HPV-associated OPC who received definitive concurrent chemoradiotherapy (CRT) with 70Gy at a single institution. Patients were followed post-CRT and their surveillance scans were recorded. Recurrences were classified as detected by first post-treatment scans, surveillance scans, clinical exams, or incidental findings. The number of surveillance scans needed to detect 1 recurrence was determined by dividing the number of surveillance scans by the number of recurrences detected by surveillance scans. Among 276 patients with a median follow-up of 39.9 months, there were 28 recurrences. Of all recurrences, 11 (39.3%) were detected by the first post-treatment scan, 11 (39.3%) by surveillance scan, 5 (17.9%) by clinical exam, and 1 (3.6%) was incidentally found. A total of 694 surveillance scans were taken. The number of surveillance scans needed to detect 1 recurrence was 64 overall, 45 within 2 years, and 248 beyond 2 years from treatment. First post-treatment scans and surveillance scans detected more recurrences than clinical exams. A high burden of surveillance scans is needed to detect 1 recurrence, especially beyond 2 years from treatment.

Predicting osteoradionecrosis risk in patients with locoregionally advanced nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy: The value of the CARWL index.

Osteoradionecrosis (ORN) is a severe complication that can arise in patients with nasopharyngeal carcinoma due to the aggressive nature of chemoradiotherapy treatment. The purpose of our study was to assess the utility of the recently introduced CARWL index, which integrates the C-reactive protein-to-albumin ratio (CAR) and significant weight loss (SWL), in predicting the risk of ORN in patients with locoregionally advanced nasopharyngeal cancer (LA-NPC) undergoing concurrent chemoradiotherapy (CCRT). We conducted a retrospective cohort analysis on 304 patients with LA-NPC treated with CCRT. Patients were categorized into CARWL index groups based on CAR (cut-off: 3.0) and SWL (weight loss > 5% over the past six months): CARWL-0 (CAR < 3.0, SWL ≤ 5%), CARWL-1 (CAR < 3.0 with SWL > 5% or CAR ≥ 3.0 with SWL ≤ 5%), and CARWL-2 (CAR ≥ 3.0 and SWL > 5%). The primary endpoint was the incidence of ORN in each CARWL index group. At a median follow-up of 67.2 months, 28 patients (9.2%) developed ORN. The incidence of ORN was 2.1%, 9.4%, and 16.3% in the CARWL-0, CARWL-1, and CARWL-2 groups, respectively (P < 0.001). Multivariate analysis identified smoking status (HR: 2.58, P = 0.034), N-stage (HR: 1.96, P = 0.008), T-stage (HR: 1.84, P = 0.017), pre-CCRT tooth extraction status (HR: 5.81, P < 0.001), post-CCRT tooth extraction status (HR: 6.82, P < 0.001), mandibular V55.8 Gy (HR: 6.12, P < 0.001), and CARWL score (HR: 5.67, P = 0.002) as significant predictors of ORN. The CARWL index is a reliable predictive tool for evaluating the risk of ORN in LA-NPC patients undergoing CCRT. If further validated, its use in clinical settings could aid in the early identification of high-risk patients and enable the implementation of personalized preventive strategies.

Joint modeling of longitudinal health-related quality of life during concurrent chemoradiotherapy period and long-term survival among patients with advanced nasopharyngeal carcinoma

BackgroundTo investigate the prognosis of longitudinal health-related quality of life (HRQOL) during concurrent chemoradiotherapy (CCRT) on survival outcomes in patients with advanced nasopharyngeal carcinoma (NPC).MethodsDuring 2012–2014, 145 adult NPC patients with stage II-IVb NPC were investigated weekly using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORCT QLQ-C30) during their CCRT period. The effects of longitudinal trends of HRQOL on survival outcomes were estimated using joint modeling, and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were reported as a 10-point increase in HRQOL scores.ResultsAfter a median follow-up of 83.4 months, the multivariable models showed significant associations of longitudinal increasing scores in fatigue and appetite loss during the CCRT period with distant metastasis-free survival: 10-point increases in scores of fatigue and appetite loss domains during CCRT period were significantly associated with 75% (HR: 1.75, 95% CI: 1.01, 3.02; p = 0.047) and 59% (HR: 1.59, 95% CI: 1.09, 2.59; p = 0.018) increase in the risk of distant metastasis, respectively. The prognostic effects of the longitudinal HRQOL trend on overall survival and progress-free survival were statistically non-significant.ConclusionIncreases in fatigue and appetite loss of HRQOL during the CCRT period are significantly associated with high risks of distant metastasis in advanced NPC patients. Nutritional support and psychological intervention are warranted for NPC patients during the treatment period.

Association of MORC2 expression with progression-free survival in cervical cancer patients treated with concurrent chemoradiotherapy.

MORC family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein, and has been proposed as a prognostic biomarker associated with survival in some types of human cancer, but the role of MORC2 in cervical cancer remains unknown. Here, we investigated the role of MORC2 expression in predicting the survival outcomes of locally advanced cervical cancer patients treated with cisplatin-based concurrent chemoradiotherapy (CCRT). In this retrospectively study, we detected MORC2 immunohistochemical expression on 55 biopsies from patients who underwent CCRT. The association between the MORC2 expression and various clinicopathological characteristics were analyzed, as were association between MORC2 expression and locoregional failure and progression-free survival (PFS) of cervical cancer patients. MORC2 expression was positively associated with pelvic node metastasis and locoregional failure. Higher MORC2 expression was a significant indicator of worse PFS. Our results suggest that MORC2 expression may be a prognostic indicator in patients with locally advanced cervical cancer undergoing CCRT.

Role of Extrafascial Hysterectomy Following Concurrent Chemoradiation in Patients Diagnosed with Adenocarcinoma of Cervix Stage IB2-IIB

Role of Extrafascial Hysterectomy Following Concurrent Chemoradiation in Patients Diagnosed with Adenocarcinoma of Cervix Stage IB2-IIB

A case of metachronous triple primary carcinoma complicated with pulmonary tuberculosis: Case report and review.

Multiple primary malignant neoplasms with tuberculosis are rare. The interaction between tuberculosis and tumor remains unclear. Moreover, the treatment of multiple primary tumors combined with tuberculosis is relatively complicated. Herein, we report a case of metachronous triple primary carcinoma complicated with pulmonary tuberculosis. This report aims to analyze the clinical characteristics of 3 primary tumors combined with tuberculosis. We report the long-term survival of this patient after personalized treatment and this patient have a good quality of life. A 55-year-old male patient was diagnosed with squamous cell carcinoma of the lower thoracic esophagus (cT4bN1M0 IVA) and received concurrent chemoradiotherapy, followed by 2 cycles consolidate chemotherapy. During the follow-up, he was diagnosed with secondary tuberculosis (TB) and accepted anti-TB treatment. During anti-TB treatment, he was diagnosed with squamous cell carcinoma of the oropharynx (cT1N0M0 I P16(-)), then he received radical radiation therapy. However, within a year, the patient was diagnosed with oral squamous cell carcinoma (cT3N0M0 IIIA). He accepted an individualized chemotherapy with paclitaxel combined with capecitabine. Moreover, immunohistochemistry of the patient's 3 biopsies indicated positive P53 expression. Since the patient suffered from esophageal cancer, oropharyngeal cancer, and oral floor cancer, no tumor recurrence or metastasis was observed. And he has a good quality of life. Tuberculosis, TP53 mutation, radiotherapy, smoking, and drinking history may be risk factors for multiple primary tumors. The treatment of multiple primary tumors combined with pulmonary tuberculosis is complicated. Individualized treatment allows patients to achieve long-term survival while also having a good quality of life. Limitations in this case: surgery may be an alternative strategy for the patient, but the patient refused surgery.

Hematological Parameters at Baseline: A Novel Prognostic Factor for Cervical Cancer Patients Undergoing Concurrent Chemoradiotherapy in South India.

Introduction In cervical cancer treatment, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and albumin-globulin ratio (AGR) are being studied as potential prognostic markers for predicting the effectiveness of concurrent chemoradiotherapy (CCRT). This study aims to investigate the relationship between these biomarkers and survival outcomes in cervical cancer patients undergoing CCRT. Materials and methods This retrospective study was conducted at Amrita Institute of Medical Sciences between January 2016 and December 2019. It included patients at any stage who received definitive CCRT and were followed for at least two years post-treatment. Patients who had initial surgery and those lost to follow-up were excluded. Results The study included 123 patients with a median age of 68. Most patients had stage IIB (39%) and squamous cell carcinoma (76.4%). With a median follow-up of 56 months, the five-yearoverall survival (OS) was 66.8%, progression-free survival (PFS) was 94%, and recurrence-free survival (RFS) was 81.2%.AGR (p = 0.001), NLR (p = 0.0001), and PLR (p = 0.001) were found to be significantly associated with OS, NLR (p = 0.002) and AGR (p = 0.001) significantly affected RFS, while only PLR (p = 0.02) significantly affected PFSon univariate analysis. NLRsignificantly impacted OS (p = 0.003) and RFS(p = 0.03) on multivariate analysis. Conclusion The results of our study showed that increased NLR and elevated levels of albumin indicate a higher likelihood of mortality. Furthermore, a higher NLR was linked to an increased probability of recurrence in patients with cervical cancer who received primary treatment with CCRT. Therefore, the identification of predictive biomarkers could significantly improve the assessment of progression risk, aiding in the selection of the most suitable treatment and personalized therapy.

Durvalumab after chemoradiotherapy for locoregional recurrence of completely resected non-small-cell lung cancer (NEJ056).

Locoregional recurrence of non-small-cell lung cancer (NSCLC) after complete resection lacks standard treatment. Durvalumab after chemoradiotherapy (CRT) or CRT alone is often selected in daily clinical practice for patients with locoregional recurrence; however, the therapeutic efficacy of these treatments remains unclear, and we aimed to assess this. This retrospective observational study used data from patients with NSCLC diagnosed with locoregional recurrence after complete resection who subsequently underwent concurrent CRT followed by durvalumab (CRT-D group) or CRT alone (CRT group). We employed propensity score analysis with inverse probability treatment weighting (IPTW) to adjust for various confounders and evaluate efficacy in the CRT-D group. After IPTW adjustment, the CRT-D group contained 119 patients (64.7% male; 69.7% adenocarcinoma), and the CRT group contained 111 patients (60.5% male; 73.4% adenocarcinoma). Their mean ages were 66 and 65 years, respectively. The IPTW-adjusted median progression-free survival was 25.4 and 11.5 months for the CRT-D and CRT groups, respectively (hazard ratio, 0.44; 95% confidence interval, 0.30-0.64); the median overall survival was not reached in either group favoring CRT-D (hazard ratio, 0.49; 95% confidence interval, 0.24-0.99). Grade 3 or 4 adverse events were observed in 48.8% of patients during CRT, 10.7% after initiating durvalumab maintenance therapy in the CRT-D group, and 57.3% in the CRT group. Overall, the sequential approach of CRT followed by durvalumab is a promising treatment strategy for locoregional recurrence of NSCLC after complete resection.

Efficacy and safety of concurrent chemoradiotherapy with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma: A multi-center propensity-score matched study

BackgroundElderly patients with esophageal cancer can benefit from concurrent chemoradiotherapy (CCRT). However, the optimal concurrent chemotherapy regimen remains undetermined. We aimed to compare the efficacy and safety of CCRT with paclitaxel-based or S-1 regimens in treating elderly patients with esophageal squamous cell carcinoma (ESCC). MethodsFrom January 2016 to November 2022, a total of 349 patients aged 70 and above with ESCC were included. The patient population was divided into two treatment groups: patients receiving paclitaxel-based CCRT were allocated to the TP group, and those receiving S-1 regimen CCRT were allocated to the S-1 group. Propensity score matching (PSM) was used to balance potential biases. Survival outcomes, overall response rate, and treatment-related toxicities were assessed. ResultsAfter PSM, there were 82 patients in each group. The median follow up of the surviving patients was 42.6 months (IQR 28.0–58.8 months). The 2-year overall survival (OS) rate (71.4% vs 65.4%; log-rank P = 0.010) and progression-free survival (PFS) rate (64.4% vs 58.0%; log-rank P = 0.048) were significantly higher in the TP group. Compared with the S-1 group, the TP group experienced a higher rate of grade 3 and above hematologic toxicities, such as leukopenia (47.6% vs 15.9%, P < 0.001) and neutropenia (35.4% vs 6.1%, P < 0.001). One patient in the TP group and two patients in the S-1 group had grade 5 toxic effects. ConclusionsOur findings suggest that paclitaxel-based CCRT was well tolerated in elderly patients with ESCC and provided significant survival benefits over S-1 regimen.

Beyond complete remission: A comparative analysis of long-term laryngeal function in patients with hypopharyngeal and laryngeal cancer following radiotherapy and concurrent chemoradiation.

This study evaluates functional larynx preservation in patients with hypopharyngeal cancer (HPC) and laryngeal cancer (LC) who achieved complete remission following radiotherapy (RT) or concurrent chemoradiation (CCRT). HPC and LC patients treated with RT/CCRT from 1999 to 2017 were retrospectively analyzed. Severe late dysphagia and tracheostomy cases were assessed to determine laryngeal function. Long-term preservation rate of functional larynx and associated factors were evaluated. Of 152 patients (55 HPC, 97 LC), nine developed severe dysphagia, occurring on average 58.2 months post-treatment. HPC and cervical node metastasis significantly increased the risk of laryngeal function impairment (p < 0.001 and p = 0.014, respectively), presenting a continued decline in functional larynx preservation rate beyond 10 years. Patients with HPC and cervical node metastasis demonstrate an increased risk for long-term laryngeal function impairment despite successful oncologic outcomes. This risk extends beyond 10 years, underscoring the need for prolonged monitoring and comprehensive support.

Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial

At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. Merck Sharp & Dohme, a subsidiary of Merck & Co.

Robotic-assisted versus laparoscopic-assisted extended mesorectal excision: a comprehensive meta-analysis and systematic review of perioperative and long-term outcomes.

Concurrent neoadjuvant chemo-radiation (nCRT) with total mesorectal excision (TME) alone sometimes fails to cure lateral lymph node metastasis (LLNM). Therefore, additional lateral lymph node dissection (LLND) can help in the treatment of these patients. This is what we refer to as extended total mesorectal excision (eTME). Such operations (TME alone or eTME) can be performed using conventional laparoscopic techniques and robotic-assisted techniques as well. Our meta-analysis aims to compare the results of robot-assisted (R-eTME) versus laparoscopic-assisted extended mesorectal excision (L-eTME) in terms of short- and long-term outcomes. Databases searched using title and abstract included Medline (via PubMed), Web of Science, Scopus, and Embase, up to February 20, 2024. All studies that documented robotic versus laparoscopic procedures for extended total mesorectal excision (R-eTME versus L-eTME) and reported more than two relevant outcomes, were included in the study. Our meta-analysis demonstrates four significant outcomes (operative time, urinary complications, overall recurrence, and admission days) between the laparoscopic and robotic groups. The robotic approach shows advantages over the laparoscopic approach in these outcomes except for the operative time (minute), which was longer in the robotic group compared to the laparoscopic group. The laparoscopic group is associated with a higher overall recurrence than the robotic group with an Odds Ratio of 2(95% CI, 1-4, p = 0.05). This meta-analysis study showed that the R-eTME group had a lower recurrence rate compared to the L-eTME group. Additionally, hospital admission days increased significantly in the laparoscopic group. Other long-term outcomes did not differ significantly between the two groups. Short-term outcomes were similar, except for more urinary complications in the laparoscopic group. In conclusion, the study suggests that robotic surgery may offer advantages over laparoscopic surgery for eTME. Further research and analysis could provide further insight into the potential benefits of robotic surgery in this procedure, particularly when surgeon experience, center volume, and learning curve are taken into consideration.

Plasma Circulating HPV DNA Surveillance in a Patient With Nasopharyngeal Cancer.

Nearly one third of nasopharyngeal carcinomas (NPCs) in the United States are associated with human papillomavirus (HPV). Surveillance for Epstein-Barr virus (EBV)-negative subtypes is customarily based solely on imaging and physical examinations. We present a case of HPV-positive NPC using serial circulating tumor HPV DNA (ctHPVDNA) as a biomarker of disease status. A 58-year-old Caucasian female initially presented with T1N1M0 EBV-negative p16-positive squamous cell carcinoma of the nasopharynx and was treated with concurrent chemoradiation. Regional nodal recurrence identified 7 months post-radiotherapy was treated with salvage left neck dissection. Surveillance was supplemented using a commercially available polymerase chain reaction (PCR)-based ctHPVDNA assay. Rising ctHPVDNA levels at 9 and 10 months post salvage surgery prompted positron emission tomography (PET). Biopsy confirmed recurrence in avid right hilar and paraoesophageal lymph nodes. Following definitive radiotherapy to the involved nodes and concurrent pembrolizumab, posttreatment ctHPVDNA decreased to baseline, but then increased after 6 cycles of pembrolizumab. Follow-up PET found left mediastinal recurrence outside of the prior treatment field, which was treated with concurrent chemoradiation with cetuximab. Again, ctHPVDNA level dropped to baseline but increased 3 months postradiation. PET scan showed a left lung nodule, and the patient received systemic therapy. Plasma ctHPVDNA monitoring correlated well with disease activity in our patient with HPV-positive NPC. ctHPVDNA detected disease earlier than standard surveillance methods and allowed for earlier intervention. Larger studies are needed to validate the utility of HPV biomarker surveillance in NPC.

Bladder preservation with concurrent chemoradiotherapy for muscle-invasive bladder cancer: Retrospective comparison of three regimens

Objectives: The objectives of the study are to evaluate the oncological and functional outcomes of three bladder preservation regimens: radiotherapy alone (RT-alone group), concurrent chemoradiotherapy (CRT) using gemcitabine plus platinum (GP-RT group), and low-dose gemcitabine (LD-Gem-RT group) for muscle-invasive bladder cancer. Methods: The three oncological outcomes, bladder-intact distant metastasis-free survival (BI-DMFS), cancer-specific survival, and overall survival (OS), were compared among RT alone (n = 10), GP-RT (n = 16), and LD-Gem-RT (n = 11) groups. Treatment-related adverse events were evaluated against the Common Terminology Criteria for Adverse Events (version 5.0). In the LD-Gem-RT group, time-course changes in the domains and scales related to the quality of life were evaluated by utilizing three questionnaires. Results: Age was significantly higher in the RT alone group (84 &amp;plusmn; 7.2 years old) than in the GP-RT (74 &amp;plusmn; 9.0) and LD-Gem-RT (75 &amp;plusmn; 6.7) groups (P = 0.016). At a median follow-up of 26 months, the 2-year BI-DMFS rates were 80, 81, and 55% in the RT alone, GP-RT, and LD-Gem-RT groups, respectively, and the 2-year OS rates were 69, 62, and 81%, respectively. In the CRT groups, only the baseline CRP &amp;ge; 1.0 mg/dL was associated with poor survival outcomes. Common early-onset adverse events included diarrhea, urinary frequency, and hematotoxicity. A questionnaire survey in the LD-Gem-RT group revealed patients experienced significant deterioration in the global health status/quality of life and the physical component summary score. Conclusion: We reported the oncological and functional outcomes of bladder preservation therapy using three different regimens, yielding acceptable outcomes.