The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

[Endoscopic response evaluation in gastrointestinal cancers after neoadjuvant chemora- diotherapy].

Neoadjuvant chemoradiotherapy has emerged as the standard treatment for locally advanced rectal cancer, esophageal cancer and gastroesophageal junction cancer which can not only improve the rate of local control but also induce pathological complete response in some patients. For patients who have achieved clinical complete response after neoadjuvant therapy, the watch & wait strategy and organ preservation could reduce unnecessary surgery and minimize the risk of postoperative complications, meanwhile greatly improve patients' quality of life without affecting the oncologic outcome. At present, a variety of methods, including white light endoscopy, endoscopic forceps biopsy, image enhanced endoscopy, endoscopic ultrasound, endoscopic ultrasound guided fine needle aspiration, endoscopic submucosal dissection, artificial intelligence assisted technology, etc., have become important assistance for the evaluation of tumor response after neoadjuvant chemoradiotherapy and have been widely used in clinical practice. This review will briefly introduce the application of the endoscopic approaches mentioned above and some novel endoscopic techniques and developing trends in response evaluation for patients with locally advanced rectal cancer, esophageal cancer and gastroesophageal junction cancer patients receiving neoadjuvant chemoradiotherapy.

[Endoscopic full-thickness resection in near clinical complete response rectal cancer after neoadjuvant therapy].

Objective: To investigate the safety and feasibility of endoscopic full-thickness resection (EFTR) in the treatment of near-clinical complete response (near-cCR) rectal cancer after neoadjuvant therapy. Methods: A 74-year-old female patient with cT3N0M0 stage rectal adenocarcinoma who refused radical surgery for rectal cancer underwent neoadjuvant chemoradiotherapy (5 cycles of CapeOx chemotherapy and concurrent radiotherapy for 25 sessions) after multidisciplinary team discussion. One month after completing neoadjuvant treatment, reassessment including digital rectal examination, colonoscopy, and pelvic enhanced magnetic resonance imaging suggested near-cCR. Despite this, the patient requested rectal-preserving therapy. Subsequently, EFTR was performed five weeks after completion of neoadjuvant treatment. Postoperatively, supportive care including fasting, antimicrobial therapy, and nutritional support was provided. The patient started a liquid diet on the 6th day postoperatively and was discharged on the 13th day. Results: Pathological analysis revealed tubular adenoma with low-grade epithelial dysplasia, with negative margins and negative involvement of the base. During one-year follow-up, there were no signs of local regrowth or distant metastasis, and satisfactory anal function was observed. Conclusion: EFTR is safe and feasible in patients with near-cCR rectal cancer after neoadjuvant therapy. This approach should be considered after thorough evaluation of the patient's condition.

Conditional survival and annual hazard of death in older patients with esophageal cancer receiving definitive chemoradiotherapy.

BACKGROUND: Definitive chemoradiotherapy is one of the primary treatment modalities for older patients with esophageal cancer (EC). However, the evolution of prognosis over time and the factors affected non-EC deaths remain inadequately studied. We examined the conditional survival and annual hazard of death in older patients with EC after chemoradiotherapy. METHODS: We collected data from patients aged 65 or older with EC registered in the Surveillance, Epidemiology, and End Results database during 2000-2019. Conditional survival was defined as the probability of survival given a specific time survived. Annual hazard of death was defined the yearly event rate. Restricted cubic spline (RCS) analysis identified the association of age at diagnosis with mortality. RESULTS: Among 3739 patients, the 3-year conditional overall survival increased annually by 7-10%. Non-EC causes accounted for 18.8% of deaths, predominantly due to cardio-cerebrovascular diseases. The hazard of death decreased from 40 to 10% in the first 6 years and then gradually increased to 20% in the tenth year. Non-EC causes surpassed EC causes in hazard starting 5 years post-treatment. RCS indicated a consistent increase in death hazard with advancing age, following a linear relationship. The overall cohort was divided into two groups: 65-74 and ≥ 75 years old, with the ≥ 75-year-old group showing poorer survival and earlier onset of non-EC deaths (HR = 1.36, 95% CI: 1.15-1.62, P < 0.001). Patients with early-stage disease (I-II) had higher risks of death from non-EC causes (HR = 0.82, 95% CI: 0.68-0.98, P = 0.035). Tumor histology had no significant impact on non-EC death risk (HR = 1.17, 95% CI: 0.98-1.39, P = 0.081). CONCLUSIONS: Survival probability increases with time for older patients with EC treated with chemoradiotherapy. Clinicians and patients should prioritize managing and preventing age-related comorbidities, especially in older cohorts and those with early-stage disease.

Radiotherapy plus temozolomide with or without anlotinib in H3K27M-mutant diffuse midline glioma: A retrospective cohort study.

BACKGROUND: Besides the hallmark of H3K27M mutation, aberrant amplifications of receptor tyrosine kinases (RTKs) are commonly observed in diffuse midline glioma (DMG), a highly malignant brain tumor with dismal prognosis. Here, we intended to evaluate the efficacy and safety of a multitarget RTK inhibitor anlotinib in patients with H3K27M-DMG. METHODS: A total of 40 newly diagnosed H3K27M-DMG patients including 15 with anlotinib and 25 without anlotinib treatment were retrospectively enrolled in this cohort. Progression-free survival (PFS), overall survival (OS), and toxicities were assessed and compared. RESULTS: The median PFS and OS of all patients in this cohort were 8.5 months (95% CI, 6.5-11.3) and 15.5 months (95% CI, 12.6-17.1), respectively. According to the Response Assessment in Neuro-Oncology (RANO) criteria, the disease control rate in the anlotinib group [93.3%, 95% confidence interval (CI), 70.2-98.8] was significantly higher than those without anlotinib (64%, 95% CI: 40.5-79.8, p = 0.039). The median PFS of patients with and without anlotinib was 11.6 months (95% CI, 7.8-14.3) and 6.4 months (95% CI, 4.3-10.3), respectively. Both the median PFS and OS of DMG patients treated with anlotinib were longer than those without anlotinib in the infratentorial patients (PFS: 10.3 vs. 5.4 months, p = 0.006; OS: 16.6 vs. 8.7 months, p = 0.016). Multivariate analysis also indicated anlotinib (HR: 0.243, 95% CI: 0.066-0.896, p = 0.034) was an independent prognosticator for longer OS in the infratentorial subgroup. In addition, the adverse events of anlotinib administration were tolerable in the whole cohort. CONCLUSIONS: This study first reported that anlotinib combined with Stupp regimen is a safe and feasible regimen for newly diagnosed patients with H3K27M-DMG. Further, anlotinib showed significant efficacy for H3K27M-DMG located in the infratentorial region.

Six versus four or five cycles of first-line etoposide and platinum-based chemotherapy combined with thoracic radiotherapy in patients with limited-stage small-cell lung cancer: A propensity score-matched analysis of a prospective randomized trial.

OBJECTIVES: The recommended treatment for limited-stage small-cell lung cancer (LS-SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4-6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS-SCLC who received either 6 cycles or 4-5 cycles of EP chemotherapy combined with TRT. MATERIALS AND METHODS: In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS-SCLC patients who received 4-6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4-5 cycles. To assess overall survival (OS) and progression-free survival (PFS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: Among the 265 LS-SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4-5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4-5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6-53.1 months) vs. 22.7 months (95% CI, 20.8-29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7-30.5 months) vs. 12.0 months (95% CI, 9.8-14.2 months), respectively, p = 0.006]. The two-year and five-year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4-5 cycles group, respectively. CONCLUSION: Patients diagnosed with LS-SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4-5 cycles.

Prognostic implications of combining EGFR-TKIs and radiotherapy in Stage IV lung adenocarcinoma with 19-Del or 21-L858R mutations: A real-world study.

OBJECTIVE: To elucidate the potential benefits of combining radiotherapy and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) for individuals with Stage IV lung adenocarcinoma (LUAD) harboring either exon 19 deletion (19-Del) or exon 21 L858R mutation (21-L858R). METHODS: In this real-world retrospective study, 177 individuals with Stage IV LUAD who underwent EGFR-TKIs and radiotherapy at Shandong Cancer Hospital from June 2012 to August 2017 were included. The main focus of this real-world study was overall survival (OS). RESULTS: The clinical characteristics of patients with Stage IV LUAD harboring 19-Del were similar to those harboring 21-L858R (p > 0.05). Overall, the patients had a median OS (mOS) of 32.0 months (95% confidence interval [CI]: 28.6-35.5). Subsequently, multivariate analysis indicated that both EGFR mutations and thoracic radiotherapy were independent predictors of OS (p = 0.001 and 0.013). Furthermore, subgroup analysis highlighted a longer OS for the 19-Del group compared to the 21-L858R group, especially when EGFR-TKIs were combined with bone metastasis or thoracic radiotherapy (mOS: 34.7 vs. 25.1 months and 51.0 vs. 29.6 months; p = 0.0056 and 0.0013, respectively). However, no significant differences were found in OS when considering patients who underwent brain metastasis radiotherapy (mOS: 34.7 vs. 25.1 months; p = 0.088). CONCLUSIONS: Patients with Stage IV LUAD harboring 19-Del experience a notably prolonged OS following combined therapy with EGFR-TKIs and radiotherapy, while this OS benefit is observed despite the absence of substantial differences in the clinical characteristics between the 19-Del and 21-L858R groups.

Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC): a prospective cohort study protocol.

INTRODUCTION: Radical chemoradiotherapy represents the gold standard for locally advanced cervical cancer. However, despite significant progress in improving local tumour control, distant relapse continues to impact overall survival. The development of predictive and prognostic biomarkers is consequently important to risk-stratify patients and identify populations at higher risk of poorer treatment response and survival outcomes. Exploratory study of using Magnetic resonance Prognostic Imaging markers for Radiotherapy In Cervix cancer (EMPIRIC) is a prospective exploratory cohort study, which aims to investigate the role of multiparametric functional MRI (fMRI) using diffusion-weighed imaging (DWI), dynamic contrast-enhanced (DCE) and blood oxygen level-dependent imaging (BOLD) MRI to assess treatment response and predict outcomes in patients undergoing radical chemoradiotherapy for cervical cancer. METHODS AND ANALYSIS: The study aims to recruit 40 patients across a single-centre over 2 years. Patients undergo multiparametric fMRI (DWI, DCE and BOLD-MRI) at three time points: before, during and at the completion of external beam radiotherapy. Tissue and liquid biopsies are collected at diagnosis and post-treatment to identify potential biomarker correlates against fMRI. The primary outcome is to evaluate sensitivity and specificity of quantitative parameters derived from fMRI as predictors of progression-free survival at 2 years following radical chemoradiotherapy for cervical cancer. The secondary outcome is to investigate the roles of fMRI as predictors of overall survival at 2 years and tumour volume reduction across treatment. Statistical analyses using regression models and survival analyses are employed to evaluate the relationships between the derived parameters, treatment response and clinical outcomes. ETHICS AND DISSEMINATION: The EMPIRIC study received ethical approval from the NHS Health Research Authority (HRA) on 14 February 2022 (protocol number RD2021-29). Confidentiality and data protection measures are strictly adhered to throughout the study. The findings of this study will be disseminated through peer-reviewed publications and scientific conferences, aiming to contribute to the growing body of evidence on the use of multiparametric MRI in cervical cancer management. TRIAL REGISTRATION NUMBER: NCT05532930.

Radiomics signature for dynamic changes of tumor-infiltrating CD8+ T cells and macrophages in cervical cancer during chemoradiotherapy.

BACKGROUND: Our previous study suggests that tumor CD8+ T cells and macrophages (defined as CD68+ cells) infiltration underwent dynamic and heterogeneous changes during concurrent chemoradiotherapy (CCRT) in cervical cancer patients, which correlated with their short-term tumor response. This study aims to develop a CT image-based radiomics signature for such dynamic changes. METHODS: Thirty cervical squamous cell carcinoma patients, who were treated with CCRT followed by brachytherapy, were included in this study. Pre-therapeutic CT images were acquired. And tumor biopsies with immunohistochemistry at primary sites were performed at baseline (0 fraction (F)) and immediately after 10F. Radiomics features were extracted from the region of interest (ROI) of CT images using Matlab. The LASSO regression model with ten-fold cross-validation was utilized to select features and construct an immunomarker classifier and a radiomics signature. Their performance was evaluated by the area under the curve (AUC). RESULTS: The changes of tumor-infiltrating CD8+T cells and macrophages after 10F radiotherapy as compared to those at baseline were used to generate the immunomarker classifier (AUC= 0.842, 95% CI:0.680-1.000). Additionally, a radiomics signature was developed using 4 key radiomics features to predict the immunomarker classifier (AUC=0.875, 95% CI:0.753-0.997). The patients stratified based on this signature exhibited significant differences in treatment response (p = 0.004). CONCLUSION: The radiomics signature could be used as a potential predictor for the CCRT-induced dynamic alterations of CD8+ T cells and macrophages, which may provide a less invasive approach to appraise tumor immune status during CCRT in cervical cancer compared to tissue biopsy.

Lymph node volume predicts survival in esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery.

Large primary tumor volume has been identified as a poor prognostic factor of esophageal squamous cell carcinoma (ESCC) treated with definitive concurrent chemoradiotherapy (CCRT). However, when neoadjuvant CCRT and surgery are adopted, the prognostic impact of primary tumor and lymph node (LN) volume on clinical outcomes in ESCC remains to be elucidated. This study included 107 patients who received neoadjuvant CCRT and surgery for ESCC. The volume of the primary tumor and LN was measured using radiotherapy planning computed tomography scans, and was correlated with overall survival (OS), disease-free survival (DFS), and cancer failure pattern. The median OS was 24.2 months (IQR, 11.1-93.9) after a median follow-up of 18.4 months (IQR, 8.1-40.7). The patients with a baseline LN volume > 7.7 ml had a significantly worse median OS compared to those with smaller LN volume (18.8 vs. 46.9 months, p = 0.049), as did those with tumor regression grade (TRG) 3-5 after CCRT (13.9 vs. 86.7 months, p < 0.001). However, there was no association between OS and esophageal tumor volume (p = 0.363). Multivariate analysis indicated that large LN volume (HR 1.753, 95% CI 1.015-3.029, p = 0.044) and high TRG (HR 3.276, 95% CI 1.556-6.898, p = 0.002) were negative prognostic factors for OS. Furthermore, large LN volume was linked to increased locoregional failure (p = 0.033) and decreased DFS (p = 0.041). In conclusion, this study demonstrated that large LN volume is correlated with poor OS, DFS, and locoregional control in ESCC treated with neoadjuvant CCRT and esophagectomy.

Durvalumab in combination with chemoradiotherapy in patients with head and neck squamous cell carcinoma: Results from the Phase 1 CLOVER study.

BACKGROUND: The Phase 1 CLOVER study (NCT03509012) assessed durvalumab in combination with concurrent chemoradiotherapy (cCRT) in patients with advanced solid tumors; we report results from the head and neck squamous cell carcinoma (HNSCC) cohort. METHODS: Patients with histologically/cytologically confirmed locally advanced HNSCC, eligible for definitive cCRT and not considered for primary surgery, received durvalumab plus cisplatin and concurrent external beam radiation. Objectives were to assess safety/tolerability and preliminary efficacy. RESULTS: Eight patients were enrolled. The most frequent any-cause adverse events (AEs) were nausea and radiation skin injury (each n = 5); most frequent grade 3/4 AEs were lymphopenia and stomatitis (each n = 3). No patients had dose-limiting toxicities. Objective response rate was 71.4% (5/7 patients; four complete responses, one partial response); disease control rate was 85.7% at 18 weeks and 83.3% at 48 weeks. CONCLUSIONS: Durvalumab plus cCRT was tolerable and active in patients with unresected, locally advanced HNSCC.

Image-based artificial intelligence for the prediction of pathological complete response to neoadjuvant chemoradiotherapy in patients with rectal cancer: a systematic review and meta-analysis.

OBJECTIVE: Artificial intelligence (AI) holds enormous potential for noninvasively identifying patients with rectal cancer who could achieve pathological complete response (pCR) following neoadjuvant chemoradiotherapy (nCRT). We aimed to conduct a meta-analysis to summarize the diagnostic performance of image-based AI models for predicting pCR to nCRT in patients with rectal cancer. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A literature search of PubMed, Embase, Cochrane Library, and Web of Science was performed from inception to July 29, 2023. Studies that developed or utilized AI models for predicting pCR to nCRT in rectal cancer from medical images were included. The Quality Assessment of Diagnostic Accuracy Studies-AI was used to appraise the methodological quality of the studies. The bivariate random-effects model was used to summarize the individual sensitivities, specificities, and areas-under-the-curve (AUCs). Subgroup and meta-regression analyses were conducted to identify potential sources of heterogeneity. Protocol for this study was registered with PROSPERO (CRD42022382374). RESULTS: Thirty-four studies (9933 patients) were identified. Pooled estimates of sensitivity, specificity, and AUC of AI models for pCR prediction were 82% (95% CI: 76-87%), 84% (95% CI: 79-88%), and 90% (95% CI: 87-92%), respectively. Higher specificity was seen for the Asian population, low risk of bias, and deep-learning, compared with the non-Asian population, high risk of bias, and radiomics (all P < 0.05). Single-center had a higher sensitivity than multi-center (P = 0.001). The retrospective design had lower sensitivity (P = 0.012) but higher specificity (P < 0.001) than the prospective design. MRI showed higher sensitivity (P = 0.001) but lower specificity (P = 0.044) than non-MRI. The sensitivity and specificity of internal validation were higher than those of external validation (both P = 0.005). CONCLUSIONS: Image-based AI models exhibited favorable performance for predicting pCR to nCRT in rectal cancer. However, further clinical trials are warranted to verify the findings.

MRI-based volumetric tumor parameters before and during chemoradiation predict tumor recurrence and patient survival in locally advanced cervical cancer: a subgroup analysis of a phase II prospective trial.

BACKGROUND: This subgroup analysis of a prospective phase II trial aimed to identify valuable and accessible prognostic factors for overall survival (OS) and progression-free survival (PFS) of patients with locally advanced cervical cancer (LACC). METHODS: Patients with FIGO II to IVA cervical cancer were assessed in this study. All patients underwent concurrent chemoradiotherapy (CCRT) followed by brachytherapy. Tumor parameters based on MRI scans before and during CCRT were evaluated for Overall survival (OS) and Progression-free survival (PFS). RESULTS: A total of 86 patients were included in this analysis with a median follow-up period of 31.7 months. Three-year OS and PFS rates for all patients were 87.1% and 76.5%, respectively. Univariate Cox regression analysis showed that restaging tumor size (rTS) over 2.55 cm (p < 0.001), initial tumor volume (iTV) over 55.99 cc (p < 0.001), downstaging (p = 0.042), and restaging tumor volume (rTV) over 6.25 cc (p = 0.006) were significantly associated with OS. rTS (p < 0.001), iTV (p < 0.001), downstaging (p = 0.027), and rTV (p < 0.001) were identified as significant prognostic factors for PFS. In the stepwise multivariable analysis, only rTS > 2.55 cm showed statistically significant with OS (HR: 5.47, 95% CI 1.80-9.58, p = 0.035) and PFS (HR: 3.83, 95% CI 1.50-11.45; p = 0.025). CONCLUSIONS: Initial tumor size and restaging tumor volume that are easily accessible during radiotherapy provide valuable prognostic information for cervical cancer. MRI-based measurable volumetric scoring system can be readily applied in real-world practice of cervical cancer. CLINICAL TRIAL INFORMATION: This study is a subgroup analysis of prospective trial registered at ClinicalTrials.gov Identifier: NCT02993653.

Less than whole uterus irradiation for patients with locally advanced cervical cancer.

INTRODUCTION: Current consensus guidelines for definitive cervical cancer intensity modulated radiation therapy (IMRT) recommend inclusion of the entire uterus within the clinical target volume, however this is debated. We aimed to evaluate outcomes of patients with cervical cancer who were treated with less than whole uterus irradiation. METHODS: We identified 109 patients with FIGO Stage IB-IVA cervical cancer treated definitively with concurrent chemoradiation, including IMRT and brachytherapy, from 2010 to 2022 at a single institution where the practice was to include the gross cervix tumor with an internal target volume with differences in bladder filing accounted for, plus additional 5 mm planning target volume (PTV) margin. Local, regional, and distant recurrences were analyzed using competing risk methods, and a Wilcoxon rank sum test was performed to assess differences in dose to organs at risk based on the proportion of the uterus included in the PTV, with the median proportion of the uterus included (75 %) used as the cut-point. RESULTS: The median follow-up time was 65 months (range 3-352 months). The 2-year cumulative incidence of LR for the entire cohort was 4.2 % (95 % confidence interval [CI] 1.3-9.7). Compared with patients who had ≥ 75 % of the uterus included in the PTV, patients who had < 75 % of the uterus included in the PTV had significantly lower bowel D200cc (p = 0.02). The cumulative incidence of local failure (LR) was not significantly different between the two groups. CONCLUSIONS: Including less than the whole uterus for definitive cervix cancer IMRT does not seem to compromise local control. Less than whole uterus irradiation could be considered for carefully selected cervix cancer patients to decrease bowel dose and possible treatment-related toxicity.

Long-term outcomes of definitive radiation with volumetric modulated arc therapy and concurrent chemotherapy for squamous cell carcinoma of the anus in a regional Australian cancer centre.

INTRODUCTION: Concurrent chemoradiotherapy is the standard of care in the curative intent treatment of squamous cell carcinoma (SCC) of the anus. Volumetric arc therapy (VMAT) is a highly conformal radiation therapy technique that has been implemented to reduce toxicity for these patients. However, there are few reports evaluating the long-term outcomes of VMAT. Thus, we evaluated the survival and toxicity outcomes of anal cancer patients treated in our regional cancer centre undergoing curative intent chemoradiotherapy using VMAT and following the Australian EviQ guidelines. METHODS: All consecutive patients treated with the VMAT technique for curative-intent definitive chemoradiotherapy for anal SCC at our institution from 2013 until 2022 were retrospectively reviewed for survival and toxicity outcomes. Kaplan-Meier estimates of locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were obtained. RESULTS: In total, 44 patients were analysed. The median follow-up was 48.9 months (Range 7.8-107). 97.7% of patients completed the prescribed radiation therapy and 88.6% chemotherapy. Five patients (11.4%) recurred. Four (9.1%) had isolated local failures, and one (2.3%) had an isolated distant failure. There were no regional nodal failures. The Kaplan-Meier estimates for locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were 90.3%, 97.7%, 88.1%, 97.1% and 87% at 3 years, and 90.3%, 97.7%, 88.1%, 93.0% and 72.3% at 5 years, respectively. Acute grade 3 genitourinary (GU), gastrointestinal (GI) and skin toxicities occurred in 2.2%, 6.8% and 13.6% of patients, respectively. There were no acute grade 4 toxicities. Late grade 2 GU and GI toxicities occurred in 6.8% and 11.3% of patients, respectively. There were no late grade 3 or 4 toxicities or treatment-related deaths. The 5 -year colostomy-free survival rate was 86.4%. CONCLUSION: Outcomes for anal SCC after definitive chemoradiotherapy using VMAT in our regional cancer centre results in low rates of grade 3/4 toxicity, high rates of organ preservation and excellent survival outcomes.

Durvalumab in combination with chemoradiotherapy for patients with unresectable stage III non-small-cell lung cancer: Results from the phase 1 CLOVER study.

INTRODUCTION: For patients with unresectable, stage III non-small-cell lung cancer (NSCLC), current standard of care is concurrent chemoradiotherapy (cCRT) followed by consolidation durvalumab. However, earlier initiation of durvalumab simultaneously with cCRT may increase antitumor activity relative to initiation after cCRT. The phase 1 CLOVER study (NCT03509012) evaluated durvalumab combined with cCRT in patients with advanced solid tumors; we report findings from the NSCLC cohort. METHODS: CLOVER comprised a dose-limiting toxicity (DLT) assessment part, followed by an expansion part. In the NSCLC cohort, patients with previously untreated, unresectable, stage III NSCLC were enrolled in three treatment arms: durvalumab every 4 weeks (Q4W) + cisplatin + etoposide + radiotherapy (Arm 1); durvalumab Q4W + carboplatin + paclitaxel + radiotherapy (Arm 2); or durvalumab Q4W + carboplatin or cisplatin + pemetrexed + radiotherapy (non-squamous histology only; Arm 3). Patients received durvalumab until disease progression or unacceptable toxicity. The primary endpoint was safety and tolerability. RESULTS: Sixty-four patients were enrolled: 21, 22, and 21 in Arms 1, 2, and 3, respectively. One patient in Arm 1 had DLT (grade 3 aspartate aminotransferase increase and grade 4 alanine aminotransferase increase); no DLTs were observed in Arms 2 or 3. Grade 3/4 adverse events occurred in 76.6 % of patients overall; the most common were neutropenia (51.6 %), leukopenia (20.3 %), and anemia (17.2 %). In a post-hoc analysis, 7.8 % of patients had grade 3 pneumonitis/radiation pneumonitis (grouped term) events. Overall, the objective response rate was 60.9 % (95 % confidence interval [CI], 47.9-72.9); median duration of response was 15.8 months (95 % CI, 9.0-not estimable [NE]). Median progression-free survival was 13.4 months (95 % CI, 8.8-20.1) and median overall survival was not reached (95 % CI, 21.9-NE). CONCLUSION: Durvalumab in combination with cCRT was well tolerated, with a manageable safety profile and showed encouraging antitumor activity in patients with unresectable, stage III NSCLC.

Comparison of the Clinical Outcomes of Esophagectomy and Concurrent Chemoradiotherapy in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma.

Background/Aims: The efficacy of concurrent chemoradiotherapy (CCRT) or esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC) is unclear. This study compared the survival and recurrence of patients with locally advanced ESCC after definitive CCRT and surgery. Methods: A retrospective study was conducted on patients with locally advanced ESCC who underwent CCRT or esophagectomy at Kosin University Gospel Hospital from January 2010 to December 2016. The patients' baseline characteristics, pathology, recurrence rate, and three-year/five-year overall survival were obtained. Results: This study evaluated ESCC patients with cT1-T2, N+ or cT3-T4, or N, who were treated by definitive CCRT (n=14) or esophagectomy (n=32). No significant difference was noted between the two groups, except for the location of the cancer and performance state. The respective three- and five-year overall survival rates were 30.8% and 23.1% in the CCRT group and 40.2% and 22.5% in the esophagectomy group (p=0.685). In the CCRT group, three patients (21.4%) had a complete response, and two (66.7%) had a recurrence. In the esophagectomy group, an R0 resection was achieved in 28 (87.5%) patients, and a recurrence occurred in 18 (64.3%). The median disease-free survival in the CCRT and esophagectomy groups was 14 and 17 months, respectively (p=0.882). Conclusions: These results showed no significant difference in survival between the definitive CCRT and surgery as the initial treatment. Nevertheless, larger prospective studies will be needed because of the retrospective nature and small number of patients in this study.

Non-operative management in low-lying rectal cancers undergoing chemoradiation.

PURPOSE: To evaluate the outcomes of post-neoadjuvant chemoradiation (NACTRT) wait-and-watch Strategy (WWS) in distal rectal cancers. MATERIALS AND METHODS: All consecutive patients from December 2012 to 2019 diagnosed with distal rectal tumors (T2-T4 N0-N+) having a complete or near-complete response (cCR or nCR, respectively) post-NACTRT and wishing for the non-surgical treatment option of WWS were included in this study. Patients were observed with 3 monthly magnetic resonance imaging (MRIs), sigmoidoscopies, and digital rectal examination for 2 years and 6 monthly thereafter. Organ preservation rate (OPR), local regrowth rate (LRR), non-regrowth recurrence-free survival (NR-RFS) and overall survival (OAS) were estimated using the Kaplan-Meier method, and factors associated with LRR were identified on univariate and multivariate analysis using the log-rank test (P < 0.05 significant). RESULTS: Sixty-one consecutive patients post-NACTRT achieving cCR[44 (72%)] and nCR[17 (28%)], respectively, were identified. All patients received pelvic radiotherapy at a dose of 45-50Gy conventional fractionation and concurrent capecitabine. An additional boost dose with either an external beam or brachytherapy was given to 39 patients. At a median follow-up of 39 months, 11 (18%) patients had local regrowth, of which seven were salvaged with surgery and the rest are alive with the disease, as they refused surgery. The overall OPR, NR-RFS, and OS were 83%, 95%, and 98%, respectively. Seven (11%) patients developed distant metastasis, of which six underwent metastatectomy and are alive and well. LRR was higher in patients with nCR versus cCR (P = 0.05). CONCLUSION: The WWS is a safe non-operative alternative management for selected patients attaining cCR/nCR after NACTRT with excellent outcomes.

Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Predicting Complete Pathological Response in Rectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy.

BACKGROUND Pathologic response after neoadjuvant therapy has been shown to improve outcomes in rectal cancer. Inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), have been studied to predict pathologic response and survival. This study aimed to evaluate the association between NLR and pathological response as well as outcome in patients with rectal cancer who underwent neoadjuvant chemoradiotherapy (nCRT). MATERIAL AND METHODS We retrospectively analyzed 187 patients with rectal cancer treated with nCRT followed by surgery between 2016 and 2020. The NLR was calculated using archival complete blood count records. Postoperative pathology reports were recorded. The NLR cut-off was determined by receiver operating characteristic curve. Kaplan-Meier survival curves and univariate and multivariate Cox regression analyses were used to analyze the relationship between NLR and clinicopathologic data to predict survival and prognosis. RESULTS An NLR >3.63 at diagnosis was the optimal cut-off value for predicting progression. Near-complete response rates were higher in patients with NLR <3.63 (38%) than in those with NLR >3.63 (18%) (P=0.035). The NLR <3.63 group had a significantly higher 5-year progression-free survival rate compared to the NLR >3.63 group (63.6% vs 40.1%, respectively; P=0.007). The NLR <3.63 group also had a higher 5-year overall survival (OS) rate than the NLR >3.63 group (72.3% vs 63.1%, respectively), but the difference was not statistically significant (P=0.077). CONCLUSIONS Our study showed a higher near-complete response rate in rectal cancer patients with NLR <3.63 receiving nCRT. This finding supports that a low preoperative NLR is a good prognostic factor in indicating pathological response.

Current and future perspectives in unresectable locally advanced esophageal squamous cell cancer (Review).

Definitive concurrent chemoradiotherapy has been the main standard treatment method for unresectable locally advanced esophageal squamous cell cancer (ESCC) since 1999. However, several disadvantages continue to be associated with this type of treatment, including a high local failure rate (reaching ~50% within 3 years) and a median overall survival (OS) time of 16.9 months. In addition, the 5­year overall survival rate of patients remains relatively low, at only ~21% for patients with ESCC with TNM stage T1­3N0­1M0. Burgeoning clinical trials and continually updating treatment modalities are currently in the process of being developed for the treatment of unresectable locally advanced ESCC. Compared with definitive concurrent chemoradiotherapy alone, clinical trials that have examined the efficacy of induction therapy, consolidation therapy, immunotherapy and targeted therapy have observed a prolonged median progression­free survival and OS. Salvage surgery can also bring benefits to some patients. Therefore, the present review aimed to provide a comprehensive overview on the latest progress that is being made in the development of treatment strategies for unresectable locally advanced ESCC, taking into account the several new challenges that need to be overcome.