Postoperative Chemoradiotherapy Research Articles

Gastric Radiotherapy in the UK – Current Practice and Opinion on Future Directions

Gastric radiotherapy (RT) is more commonly practiced in the US compared to the UK, where postoperative chemoradiotherapy (CRT) is reserved for selected high-risk patients, and preoperative CRT is not standard of care pending the results of phase 3 trials, TOPGEAR and CRITICSII. CRT for inoperable, non-metastatic gastric cancer is also not recommended in the UK, despite being listed in NCCN guidelines. Recent systematic review of definitive gastric CRT (dCRT) conducted by the authors found median overall survival of 11-26.4 months, clinical complete response rates of 8-45% and acceptable rates of ≥G3 toxicity, supporting further research. Given these promising findings and perceived low uptake of gastric RT in the UK, we set out to establish current UK practice, opinion and RT technique to inform the development of a UK gastric RT protocol and future clinical trials. A 19 question survey was developed. Following local ethical approval and pilot by 4 clinical oncologists, the final survey was distributed electronically on 13/12/22 to UK Consultant Clinical Oncologists specializing in esophago-gastric (OG) cancer. Responses were anonymous. Survey was closed 6/2/23 and data analyzed using JISC/spreadsheet software. A total of 43 clinicians completed the survey. For gastric cancer, 28.6%, 7.1% and 9.5% would agree/strongly agree with use of postoperative (postopRT), preoperative (preopRT) or definitive RT (dRT) respectively, compared to 26.2%, 45.2% and 46.6% for type III gastro-esophageal junction tumors. 93% had prescribed palliative gastric RT in the last 3 years compared to 40.5% postopRT, 16.7% dRT and 9.5% preopRT. Main reasons for infrequent use were; rarely indicated within standard UK practice 88.4%, lack of UK gastric RT protocol 53.5%, toxicity concerns 44.2%. 45Gy/25# was most commonly used for preopRT (66%) and postopRT (86%), and 50Gy/25# for dRT (58%). 96% use IMRT/VMAT, 85% CT simulation with IV/oral contrast, 69% gastric filling protocol and 54% 4DCT. When ranked out of 10 (1 = low 10 = high), clinician confidence in accurately delineating gastric volumes mean rank was 4.33 for postopRT, with 9% rating ≥8/10, and 4.52 for dCRT/preopRT with 17% rating ≥8/10. However, 48.8% were experienced in outlining upper abdominal nodes and 62.8% duodenum. 93% would find a detailed outlining protocol useful, 81.4% wanted some form of peer review, 76.7% a nodal atlas, and 74.4% a workshop with an expert. 77.6% would be supportive of a future clinical trial of dCRT, with 23.4% needing more supporting evidence. No-one would not support a future trial in this setting. Gastric RT is not often practiced in the UK, due to lacking evidence and toxicity concerns. Given the growing evidence and supportive OG community, it is time to consider a trial of dCRT in the UK, which must include detailed RT protocols, atlases and educational materials to improve clinician confidence and ensure good RT quality assurance.

Patterns of Failure for Poor Response to Neoadjuvant Chemotherapy in Gastric Cancer

Peri-operative chemotherapy has emerged as the standard of care in the treatment of locally advanced gastric cancer. Improved treatment strategies are needed for patients with a poor response to neoadjuvant chemotherapy and postoperative chemoradiation has been proposed as a potential method of treatment intensification. We aimed to describe the patterns of failure for patients with no or partial response (NR, PR) to pre-operative chemotherapy. We retrospectively reviewed charts of patients with locally advanced gastric cancer treated at our institution from 2008 to 2022 with pre-operative chemotherapy followed by surgery with a D2 resection. We excluded patients who received pre-operative or post-operative radiation therapy, or patients who had a complete response (CR) following neoadjuvant chemotherapy. Cumulative incidence of locoregional failure (LRF) and distant metastases (DM) were calculated from the time of diagnosis with competing risk analysis with death as a competing risk and censored at the last follow up. Overall survival (OS) was analyzed using Kaplan-Meier. A total of 57 patients were identified and 60% are male. Median follow-up time was 31.3 months (range 6.9-181.5 months), and the median age at diagnosis was 68 years old (range 30-86). The most used pre-operative chemotherapy regimen was FLOT (38.6%), followed by FOLFOX (29.8%), and ECF/ECX/EOX (19.3%), and a majority of patients (57.9%) received adjuvant chemotherapy. The most common histology was adenocarcinoma (85.9%), and 61.4% of patients had poorly differentiated disease. Thirty-three (57.9%), and 9 patients (15.8%) were characterized as PR and NR to neoadjuvant therapy by pathology, respectively. The distribution of pathologic stages following neoadjuvant chemotherapy were as follows: 17 patients (29.8%) with Stage IA-B, 12 patients (21.1%) with Stage IIA-B, 15 patients (26.3%) with Stage IIIA, 9 patients (15.8%) with Stage IIIB, and 3 patients (5.3%) with Stage IIIC disease. Two patients had positive lymph nodes with a T0 primary tumor. Median OS was 51.4 months (95% confidence interval [CI] 39.8-68.4) for the entire cohort, and 92.1 months (95% CI 34.6-73.0) versus 42.8 months (95% CI 23.1-88.0) for patients with a PR, and NR, respectively (p = 0.14). The 2-year cumulative incidence of LRF and DM was 7.4% (95% CI 0.4-14.3) and 36.3% (95% CI 23.6-49.1), respectively. Of the five patients who experienced LRF, three of the patients also eventually or concurrently developed DM. 60% of these patients would have had their first site of recurrence covered by standard post-operative radiation treatment volumes. Patients with locally advanced gastric cancer who do have less than a CR to chemotherapy have poor outcomes due to high rates of DM. Adjuvant locoregional therapy such as radiation is unlikely to affect survival while DM is the predominant pattern of progression. Further studies are needed to identify adjuvant therapies to improve distant control.

Adjuvant Concurrent Chemoradiotherapy vs. Radiotherapy Alone in Cervical Cancer Patients with Intermediate-Risk Factors after Radical Surgery

For early-stage cervical cancer patients with intermediate-risk factors, there is no consensus about whether postoperative concurrent chemoradiotherapy (CCRT) is superior to radiotherapy (RT) alone. We retrospectively reviewed medical records of stage I-IIA cervical cancer patients underwent radical surgery and postoperative RT or CCRT from June 2012 to December 2017. Patients with any of the high-risk factors including positive pelvic lymph node, positive resection margin, and parametrial invasion were excluded. Patients with any of the intermediate-risk factors including large tumor size (≥4cm), deep stromal invasion (≥1/2), and lymphovascular space involvement were included. 1:1 propensity score matching was performed to balance baseline variables between patients receiving RT and CCRT. A total of 350 patients were enrolled (84 underwent RT alone and 266 underwent CCRT). The median follow-up period was 50.4 months. For patients underwent RT alone and CCRT, the 5-year overall survival (OS) rates were 93.4% and 93.8% (p = 0.741), the 5-year disease-free survival (DFS) rates were 90.6% and 91.4% (p = 0.733), respectively. 83 pairs of patients were enrolled based on propensity score matching. Similarly, there was no significant difference between OS or DFS rates of those matched patients. For patients with single intermediate-risk factor who received RT alone (n = 58) and CCRT (n = 132), the 5-year OS rates were 94.2% and 95.7% (p = 0.636), the 5-year DFS rates were 92.8% and 94.1% (p = 0.637). For patients with multiple intermediate-risk factors who received RT alone (n = 26) and CCRT (n = 134), the 5-year OS rates were 91.8% and 91.7% (p = 0.761), the 5-year DFS rates were 85.4% and 88.4% (p = 0.717). The cox regression analysis also indicated that adjuvant CCRT or RT was not an independent prognostic factor for OS or DFS. Otherwise, patients underwent CCRT seemed to develop a higher proportion of grade 3 or higher acute hematologic toxicities than RT group (45.5% and 14.3%, p<0.001). There was no significant difference in OS and DFS between cervical cancer patients with intermediate-risk factors receiving postoperative CCRT and RT alone. Patients underwent CCRT seemed to develop a higher proportion of severe hematologic toxicities than RT alone. To a certain extent, CCRT is not superior to RT alone for intermediate-risk patients.

Predictive value of diffusion MRI-based parametric response mapping for prognosis and treatment response in glioblastoma

BackgroundEarly detection of treatment response is important for the management of patients with malignant brain tumors such as glioblastoma to assure good quality of life in relation to therapeutic efficacy. AimTo investigate whether parametric response mapping (PRM) with diffusion MRI may provide prognostic information at an early stage of standard therapy for glioblastoma. Materials and methodsThis prospective study included 31 patients newly diagnosed with glioblastoma WHO grade IV, planned for primary standard postoperative treatment with radiotherapy 60Gy/30 fractions with concomitant and adjuvant Temozolomide. MRI follow-up including diffusion and perfusion weighting was performed at 3 T at start of postoperative chemoradiotherapy, three weeks into treatment, and then regularly until twelve months postoperatively. Regional mean diffusivity (MD) changes were analyzed voxel-wise using the PRM method (MD-PRM). At eight and twelve months postoperatively, after completion of standard treatment, patients were classified using conventional MRI and clinical evaluation as either having stable disease (SD, including partial response) or progressive disease (PD). It was assessed whether MD-PRM differed between patients having SD versus PD and whether it predicted the risk of disease progression (progression-free survival, PFS) or death (overall survival, OS). A subgroup analysis was performed that compared MD-PRM between SD and PD in patients only undergoing diagnostic biopsy. MGMT-promotor methylation status (O6-methylguanine-DNA methyltransferase) was registered and analyzed with respect to PFS, OS and MD-PRM. ResultsOf the 31 patients analyzed: 21 were operated by resection and ten by diagnostic biopsy. At eight months, 19 patients had SD and twelve had PD. At twelve months, ten patients had SD and 20 had PD, out of which ten were deceased within twelve months and one was deceased without known tumor progression. Median PFS was nine months, and median OS was 17 months. Eleven patients had methylated MGMT-promotor, 16 were MGMT unmethylated, and four had unknown MGMT-status. MD-PRM did not significantly predict patients having SD versus PD neither at eight nor at twelve months. Patients with an above median MD-PRM reduction had a slightly longer PFS (P = 0.015) in Kaplan-Maier analysis, as well as a non-significantly longer OS (P = 0.099). In the subgroup of patients only undergoing biopsy, total MD-PRM change at three weeks was generally higher for patients with SD than for patients with PD at eight months, although no tests were performed. MGMT status strongly predicted both PFS and OS but not MD-PRM change. ConclusionMD-PRM at three weeks was not demonstrated to be predictive of treatment response, disease progression, or survival. Preliminary results suggested a higher predictive value in non-resected patients, although this needs to be evaluated in future studies.

LOW-GRADE GLIOMAS IN OLDER PATIENTS: A MATCHED PROPENSITY-SCORING ANALYSIS TO DETERMINE SEIZURE OUTCOMES AND PROGNOSIS

Abstract AIMS Low-grade gliomas (LGG) are associated with significant morbidity and age is assumed to be a negative prognostic factor. The aim of this study was to compare outcomes between older patients with LGGs and a matched cohort of younger patients. METHOD Retrospective review of WHO grade II LGGs from 2009-2022. Propensity-score matching (1:3 matching) was used to compare older (≥65 years old) and matched younger controls (&amp;lt;65 years old). The two groups were matched by age, gender, presenting seizures, Karnofsky performance status, location, extent of resection, use of awake neurosurgical monitoring, histology subtype and post-operative chemoradiotherapy. Survival analysis was performed using Kaplan-Meier survival curves and log-rank test. RESULTS 40 patients were included - 10 older and 30 young. The median age was 70.0 and 48.5 years, respectively, with no differences in other demographic variables. Following resection, the older group had a shorter seizure-free period (median 2.5 vs. 10.9 months) and worse 1-year seizure-free rates (25.0% vs. 50.0%). Other outcomes were also worse in the older group including a shorter overall survival (median 95.0 vs. 117.0 months) and shorter progression-free survival (median 24.0 vs. 61.0 months). CONCLUSIONS In this novel study, we present the first matched analysis to evaluate outcomes in older patients with LGGs. We report worse seizure outcomes, overall survival and progression-free survival in these patients. Larger longitudinal multicentre studies will more accurately assess post-operative seizure-control and prognostic outcomes in between these groups.

PROCARBAZINE, LOMUSTINE, VINCRISTINE FOR THE SECOND LINE TREATMENT OF GLIOBLASTOMA MULTIFORME

Abstract AIMS Most patients with glioblastoma recur despite surgery and post-operative chemoradiation. The optimal second line chemotherapy regime is not known. The aim of this study was to evaluate PCV chemotherapy given as second line treatment for glioblastoma. METHOD Data was collected for all patients with glioblastoma treated with second line PCV between 2009 and 2021 at the Norfolk and Norwich University Hospital. All underwent surgical resection either complete or incomplete resection followed by adjuvant radiotherapy and chemotherapy according to the Stupp or Perry A protocol. All received palliative PCV chemotherapy at recurrence. The Response Assessment in Neuro-Oncology (RANO) criteria were used to assess response to palliative PCV chemotherapy. Patient and disease related characteristics were described. Disease free survival from recurrence to death and survival outcomes were estimated using Kaplan-Meir method. RESULTS 70 patients were evaluated. Overall survival from surgery to death was 290 days (95%CI 245 to 318) Survival from disease progression to death was 182 days (95%CI 131 to 218). Subgroup analysis was performed for patients &amp;lt;65years and &amp;gt;65years. For patients &amp;lt;65 years N=51, median overall survival was 199 days (95%CI 142 to 353) p value 0.1246. For those &amp;gt;65 years N=16, median overall survival was 130.5 days (95%CI 93 to 227) CONCLUSIONS Using PCV as a second line chemotherapy for patients with glioblastoma is a reasonable approach. It is well tolerated and provides benefit for patients &amp;lt;65 years as well as older patients.

Clinical outcomes following observation, post-operative radiation therapy, or post-operative chemoradiation for HPV-associated oropharyngeal squamous cell carcinomas

BackgroundIntermediate and high-risk features (IRFs/HRFs) for locoregional recurrence following initial surgery for oropharyngeal SCCs (OP-SCCs) were defined prior to the known association of HPV with OP-SCC. There are limited reports on practice patterns and outcomes associated with post-operative radiation therapy (PORT) or chemoradiation (POCRT) for HPV-associated OP-SCCs. Materials/Methods:The National Cancer Database was queried for patients with HPV-associated OP-SCCs managed initially with surgery with IRFs or HRFs. IRFs were defined as pT3/T4 disease, pN1-3 disease, and lymphovascular space invasion, and HRFs as positive margins and extranodal extension (ENE). Patients were stratified into no adjuvant therapy, PORT, or POCRT arms. Kaplan-Meier analysis was utilized for comparison of overall survival (OS) between treatment arms followed by a Cox multivariate (MVA) proportional-hazards model and propensity score analyses with inverse probability treatment weighting (IPTW). ResultsWe identified 6,301 patients; 51.2% had IRFs only and 48.8% had HRFs. Regarding treatment, 25.5%, 38.2%, and 36.3% of patients received no RT, PORT, and POCRT, respectively. Patients with IRFs who did not receive RT or CRT had inferior 8-year OS (81.1% vs. 87.8%; p < 0.001) that remained significant on IPTW MVA (hazard ratio (HR) = 1.69 (95% CI: 1.27–2.24; p < 0.001). Among patients with HRFs, 8-year OS was not significantly different between patients receiving PORT vs. POCRT (77.3% vs. 79.2%; p = 0.22) that remained insignificant on IPTW MVA (HR = 0.91(0.72–1.17); p = 0.48). ConclusionA significant proportion of HPV-associated OP-SCC patients with IRFs or HRFs did not receive PORT, which was associated with inferior OS. We did not demonstrate with statistical power that POCRT vs. PORT was associated with superior OS in patients with HRFs, though prospective studies are warranted.

Survival Among Post-Operative Non-Small Cell Lung Cancer Patients Receiving Chemoradiotherapy; A Retrospective Analysis

Background: Despite being the second most frequent malignancy, lung cancer is the main reason for cancer-related fatalities. In this study, patients who underwent surgery for Non-Small Cell Lung Cancer and received adjuvant chemoradiotherapy will be evaluated. Patients and Methods: The data of 123 eligible patients who were operated with the diagnosis of Non-Small Cell Lung Cancer between 2000 and 2020 and who were treated with adjuvant chemoradiotherapy were retrospectively analyzed. Results: Of the 123 patients that were included in the study, 111 (90%) were males and 12 (10%) were females. The mean age was 62.11±8.92 (range:33-77) years. According to histological types, 65 (53%) patients were squamous cell carcinoma, 54 (44%) patients were adenocarcinoma and 4 (3%) patients were large cell carcinoma. Fifty-nine (48%) patients had undergone right lobectomy, 43 (35%) patients left lobectomy, 7 (6%) patients right pneumonectomy and 14 (11%) patients had left pneumonectomy. Mean OS time of all patients was 63.34±5.98 (51.62-75.07) months. One, 2, 3 and 5-year survival rates were 89.9%, 66.9%, 56.3% and 40.9%, respectively. There was a significant correlation between the T stage (p=0.05) of the disease and the chemotherapy protocol (p=0.046) and survival. Conclusion: Complete surgical resection remains the most effective treatment for patients with operable Non-Small Cell Lung Cancer. The high risks of distant recurrence brought on by the presence of metastatic disease that went unnoticed prior to surgery, however, restrict the effectiveness of surgical resection. Therefore, postoperative chemoradiotherapy employing constrained areas and contemporary approaches can be advantageous.

A multicenter retrospective analysis of patients with salivary gland carcinoma treated with postoperative radiotherapy alone or chemoradiotherapy

BackgroundThe aim of this study was to interrogate if the use of postoperative chemoradiotherapy (POCRT) correlated with superior oncological outcomes for certain subgroups of patients with high-risk salivary gland carcinoma (SGC), compared with postoperative radiotherapy (PORT) alone. MethodsThis multicenter retrospective study included 411 patients with surgically resected SGC who underwent PORT (n = 263) or POCRT (n = 148) between 2000 and 2015. Possible correlations of clinical parameters with outcomes were examined using the Kaplan-Meier analysis and Cox proportional-hazards regression model. ResultsThe median follow-up of survivors is 10.9 years. For the entire cohort, adding concurrent chemotherapy to PORT was not associated with OS, PFS, or LRC improvement. However, patients with nodal metastasis who underwent POCRT had significantly higher 10-year OS (46.2% vs. 18.2%, P = 0.009) and PFS (38.7% vs. 10.0%, P = 0.009) rates than those treated with PORT alone. The presence of postoperative macroscopic residual tumor (R2 resection) was identified as an independent prognosticator for inferior OS (P = 0.032), PFS (P = 0.001), and LRC (P = 0.007). Importantly, POCRT significantly correlated with higher 10-year LRC rates in patients with R2 resection (74.2% vs. 40.7%, P = 0.034) or adenoid cystic carcinoma (AdCC, 97.6% vs. 83.6%, P = 0.039). On multivariate analyses, the use of POCRT significantly predicted superior OS (P = 0.037) and PFS (P = 0.013) for node-positive patients and LRC for patients with R2 resection (P = 0.041) or AdCC (P = 0.005). ConclusionsFor surgically resected SGC, POCRT was associated with improved long-term OS and PFS for patients with nodal metastasis and superior LRC for patients with R2 resection or AdCC.

Impact of Positive-Margin Resection of External Auditory Canal Squamous Cell Carcinoma.

Positive-margin resection of external auditory canal squamous cell carcinoma (EAC-SCC) is still a major cause of recurrence. The aim of this study is to examine the clinical impact of positive-margin resection of EAC-SCCs. We retrospectively reviewed 40 surgical cases with en bloc temporal bone resection of EAC-SCC at a tertiary referral center from October 2016 to March 2022. Two-year disease-specific, overall, and disease-free survival rates for all 40 cases reviewed were 85.2%, 88.85%, and 76.96%, respectively. En bloc resection with a negative margin significantly improved patient prognosis (p < 0.001). Positive-margin resection was observed in 9/40 cases (22.5%). Insufficient assessment of preoperative images was the cause in two of these cases. Postoperative lymph node metastasis and distant metastasis were observed in cases in which vascular, lymphatic duct or perineural invasion was found on postoperative pathological examination. In addition, three cases in which no vascular, lymphatic duct, or perineural invasion was found exhibited local recurrence during the follow-up period. Of the nine positive-margin resection cases, only two showed no postoperative recurrence. Once positive-margin resections are confirmed, cases might have a high risk of tumor recurrence, even with the addition of postoperative adjuvant chemoradiotherapy.

Prevalence and Prognostic Significance of PIK3CA Mutation and CNV Status and Phosphorylated AKT Expression in Patients With Cervical Cancer Treated With Primary Surgery.

Currently, there are limited and conflicting reports on the prognostic utility of PIK3CA and associated pathway markers for cervical cancers treated with primary surgical management. Moreover, current studies are lacking complete characterization of adjuvant treatment with RT and/or chemotherapy. We aimed to document the prevalence, clinicopathologic, adjuvant treatment details, and prognostic value of PI3K/AKT pathway mutations and copy number variation and phosphorylated AKT status in patients with cervical cancers treated with primary surgery. A clinicopathologic review was performed on a retrospective cohort of 185 patients with cervical cancer, treated with primary surgery at a single tertiary institution. Next-generation sequencing and digital PCR was used to determine PI3K/AKT pathway mutational status and PIK3CA copy number variation, respectively, and fluorescent immunohistochemistry measured phosphorylated AKT expression. In all, 179 of 185 (96.8%) of tumors were successfully sequenced; 48 (26.8%) were positive for PI3K/AKT pathway mutations-the majority (n=37, 77.1%) PIK3CA mutations. PIK3CA mutation was associated with pathologically positive lymph nodes [12 (32%) vs. 22 (16%); P =0.022] and indication for postoperative chemoradiotherapy [17 (45.9%) vs. 32 (22.5%); P =0.004]. On multivariable analysis, PIK3CA status was not associated with overall survival ( P =0.103) or progression-free survival ( P =0.240) at 5yrs, nor was PIK3CA copy number variation status. phosphorylated AKT ≤ median significantly predicted for progression-free survival [multivariable hazard ratio 0.39 (0.17-0.89; P =0.025)] but not overall survival ( P =0.087). The correlation of PIK3CA with pathologic positive lymph node status yet lack of association with survival outcomes may be due to the use of adjuvant postoperative therapy. PIK3CA assessment before radical hysterectomy may help identify patients with a higher risk of node-positive disease.

Optimizing maximum resection of glioblastoma: Raman spectroscopy versus 5-aminolevulinic acid.

The objective of this study was to assess and compare the potential of 5-aminolevulinic acid (5-ALA) and Raman spectroscopy (RS) in detecting tumor-infiltrated brain in patients with glioblastoma (GBM). Between July 2020 and October 2021, the authors conducted a prospective clinical trial with 15 patients who underwent neurosurgical treatment of newly diagnosed and histologically verified GBM. A solid contrast-enhancing tumor core and peritumoral tissue were investigated intraoperatively for cancer cells by using 5-ALA and RS to achieve pathology-tailored maximum resection. In each case, a minimum of 10 biopsies were sampled from navigation-guided areas. Two neuropathologists examined the biopsies for the presence of neoplastic cells. The detection performance of 5-ALA and RS alone and in combination was assessed. Pre- and postoperative MRI, Karnofsky Performance Status (KPS), and National Institutes of Health Stroke Scale (NIHSS) scores were compared, and median progression-free survival (PFS) was evaluated. A total of 185 biopsy samples were harvested from the contrast-enhancing tumor core (n = 19) and peritumoral tissue (n = 166). In the tumor core, 5-ALA and RS each showed a sensitivity of 100%. In the peritumoral tissue, 5-ALA was less sensitive than RS in detecting cancer (46% vs 69%) but showed higher specificity (81% vs 57%). When the two methods were combined, the accuracy of tumor detection was increased by about 10%. Pathology-tailored resection led to a 52% increase in resection volume comparing the volume of preoperative contrast enhancement with the postoperative resection cavity on MRI (p = 0.0123). Eloquent brain involvement prevented gross-total resection in 4 patients. Four weeks after surgery, mean KPS (p = 0.7637) and NIHSS scores (p = 0.3146) were not significantly different from preoperative values. Of the 13 patients who had received postoperative chemoradiotherapy, 4 did not show any progression after a median follow-up of 14 months. The remaining 9 patients had a median PFS of 8 months. According to the study data, RS is capable of detecting tumor-infiltrated brain with higher sensitivity but lower specificity than the current standard of 5-ALA. With further technological and workflow advancements, RS in combination with protoporphyrin IX fluorescence may contribute to pathology-tailored glioma resection in the future.

Evaluation of Response and Toxicity in Patients with Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiation

Purpose: To study the response after neoadjuvant chemoradiation in patients with locally advanced rectal cancer with capecitabine 825 mg/m2 daily PO bid with radiation at a dose of 45Gy/20#/4 weeks, to study the clinical profile of different patients with locally advanced rectal cancer, and to assess the toxicity of patients treated with neoadjuvant chemoradiationtherapy. Materials and Methods: A prospective observational study was conducted in 60 patients with histopathologically proven locally advanced rectal carcinoma from October 2018 to April 2020 . Neoadjuvant chemoradiation was planned with capecitabine 825 mg/m2 PO bid with radiation at a dose of 45 Gy/20#/4 weeks. Radiological response was assessed 6 weeks after treatment completion, and surgery was planned according to the response. Results: Thirty-seven patients underwent definitive surgery. Pathological complete response was observed in one patient, near complete response in seven, partial response in 27, and poor or no response in two patients. Of 37 patients who have undergone surgery, 30% of patients received sphincter preserving surgery. Radiation-induced acute skin and lower gastrointestinal tract lesions were observed. Capecitabine-induced diarrhea, hematological toxicities, and a few patients with hand foot syndrome were observed. Conclusion: In locally advanced rectal cancer, preoperative radio-chemotherapy with capecitabine improves local control and reduces the risks of acute and late toxicity compared to postoperative radiochemotherapy. Thus, preoperative radiochemotherapy with capecitabine is safe and well tolerated in locally advanced rectal cancer, especially in tumors of the lower and middle rectum.

Dosimetric comparison of rectal carcinoma radiation therapy using three dimensional conformal radiation therapy and intensity modulated radiation therapy: an analytical observational study

Rectal cancer is the second most common cancer in large intestine. Recently, preoperative chemoradiotherapy has been generally used in the management of locally advanced rectal cancer on the basis of several benefits proven by clinical studies, in the aspect of better locoregional tumor control, reduced toxicity of normal organs, and an increased chance of preserving the anal sphincter, when compared with postoperative chemoradiotherapy. In this observational study, conducted between January 2017 and December 2021, pursuant to the recommendations of the radiation therapy oncology group (RTOG), all patients underwent CT simulation, a bladder protocol and target contouring. 10 patients were treated with intensity modulated radiotherapy (IMRT) and 10 with three-dimensional conformal radiation therapy (3DCRT). Planned target volume (PTV) coverage, homogeneity index (HI), conformity index (CI), and doses to organs at risk (OAR) were compared. Our findings showed that 3DCRT and IMRT have statistically significant differences in PTV coverage and dosages to OAR (p&lt;0.001), proving that IMRT achieves improved target dose coverage and superior normal tissue avoidance (bladder and intestine) compared to 3DCRT.

Therapeutic evaluation of postoperative chemotherapy and chemoradiotherapy on cardiopulmonary complications in patients with esophageal squamous cell carcinoma

Background: Postoperative chemotherapy (pCT), together with chemoradiotherapy (pCRT), is well used for the treatment of squamous cell carcinoma in the esophagus. However, these adjuvant therapies may cause serious adverse effects resulting in higher postoperative morbidity.&#x0D; Methods: In this study, we aim to assess and compare the postoperative cardiopulmonary complications as a result of pCT and pCRT in patients with esophageal cancer. PCT (n = 182) or pCRT (n = 153) was conducted to treat patients with esophageal cancer.&#x0D; Results: A significantly higher percentage of pneumonia was diagnosed in patients with the pCRT treatment compared with pCT group (P &lt; 0.01). In comparison to the pCT treated group, pCRT treatment patients showed significantly decreased early diastolic filling velocity (P &lt; 0.01) and higher plasma level of N-terminal pro-brain natriuretic peptide (NT-proBNP) (P &lt; 0.01). Moreover, pCRT treatment was associated with higher pneumonia risk and increased NT-proBNP level significantly by a multivariate analysis.&#x0D; Conclusion: pCRT treatment increased the percentage of cardiopulmonary complications in comparison with pCT treatment.

Postoperative radiotherapy alone is as effective as postoperative chemoradiotherapy in patients with pT4aN0 gingival cancer with negative surgical margins.

This study compared the survival outcomes following postoperative chemoradiotherapy (CCRT) and postoperative radiotherapy (RT) alone for patients with gingival cancer with negative surgical margins and only bone invasion. Of the 2579 gingival cancer cases reviewed from 2002 to 2018, 156 were enrolled in the study (CCRT: 63 patients; RT: 93 patients). The primary endpoints were the impact of adjuvant treatment (RT vs. CCRT) on overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS). Subgroup analyses were conducted based on surgical margins (<5 mm vs.≥5mm) and different adjuvant treatments (RT vs. CCRT). Median follow-up time, age, and invasion depth were 88.5months, 57years, and 14mm, respectively. More patients undergoing adjuvant CCRT had surgical margins<5mm (47.6% vs. 21.5%, p<0.01) than those undergoing RT. No significant difference was observed in the 5-year OS, LRRFS, and DMFS of patients undergoing adjuvant RT and CCRT. Although adjuvant RT alone and CCRT provided similar local control for patients with surgical margins≥5mm, worse LRRFS trends were observed in patients with surgical margins<5mm (hazards ratio, 6.15, 95% confidence interval 0.92-41.13, p=0.06). Postoperative RT alone may be effective for patients with gingival cancer with negative surgical margins (≥5 mm) and only bone invasion, while postoperative CCRT may result in better LRRFS than RT alone for patients with surgical margins<5mm.

Nutrition and head-neck cancer: A prospective observational study in patients with head neck cancer receiving adjuvant/definitive radiotherapy/chemoradiotherapy.

e18784 Background: Head-Neck cancers are at higher risk of malnutrition due to their disease or its treatment which can cause structural changes to the oral cavity and prevent effective nutrition. Malnutrition is assessed by anthropometric measurements. Skeletal muscle strength is also a marker of nutrition. The present study aimed to study the correlation between nutrition, muscle strength and acute toxicities in patients with head and neck squamous carcinoma receiving concurrent chemoradiotherapy or radiotherapy alone. Methods: A prospective observational study was conducted at Deenanath Mangeshkar Hospital, Pune, India in patients with nonmetastatic head neck squamous cancers planned for definitive or adjuvant chemo-radiotherapy. Nutritional status was assessed at baseline, end of treatment and after 3months of treatment by mid-arm circumference, weight, height and body mass index. Muscle strength was assessed by Jamar’s handgrip dynamometer. Results: A total of 103 patients (85 males and 18 females) participated in the study between February 2020 and February 2021. Four patients had to be withdrawn before initiating treatment, 99 patients completed the planned course of treatment. Mean age was 54.4 years. Postoperative chemoradiotherapy was give to 37 patients, 22 received definitive chemoradiotherapy, 33 received postoperative radiotherapy alone and 7 patients received definitive radiotherapy. A statistically significant reduction in all nutritional parameters during treatment and at 3 months after completion of treatment was seen. Mucositis and odynophagia were the commonest toxicities. Nasogastric or percutaneous gastrostomy tube was inserted in 25 patients. Seven patients required hospitalisation for toxicities. There were no treatment related deaths. Conclusions: Head and neck cancer patients undergoing concurrent chemoradiation or radiation are at significantly higher risk of malnutrition. Loss of muscle strength correlates with treatment related acute toxicity. [Table: see text]

Treatment and prognosis analysis of 488 patients with FIGO 2018 stage Ⅲc squamous cervical cancer

Objective: To analyze the treatment and prognosis of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage Ⅲc cervical squamous cell carcinoma. Methods: A total of 488 patients at Zhejiang Cancer Hospital between May, 2013 to May, 2015 were enrolled. The clinical characteristics and prognosis were compared according to the treatment mode (surgery combined with postoperative chemoradiotherapy vs radical concurrent chemoradiotherapy). The median follow-up time was (96±12) months ( range time from 84 to 108 months). Results: (1) The data were divided into surgery combined with chemoradiotherapy group (surgery group) and concurrent chemoradiotherapy group (radiotherapy group), including 324 cases in the surgery group and 164 cases in the radiotherapy group. There were significant differences in Eastern Cooperation Oncology Group (ECOG) score, FIGO 2018 stage, large tumors (≥4 cm), total treatment time and total treatment cost between the two groups (all P<0.01). (2) Prognosis: ① for stage Ⅲc1 patients, there were 299 patients in the surgery group with 250 patients survived (83.6%). In the radiotherapy group, 74 patients survived (52.9%). The difference of survival rates between the two groups was statistically significant (P<0.001). For stage Ⅲc2 patients, there were 25 patients in surgery group with 12 patients survived (48.0%). In the radiotherapy group, there were 24 cases, 8 cases survived, the survival rate was 33.3%. There was no significant difference between the two groups (P=0.296). ② For patients with large tumors (≥4 cm) in the surgery group, there were 138 patients in the Ⅲc1 group with 112 patients survived (81.2%); in the radiotherapy group, there were 108 cases with 56 cases survived (51.9%). The difference between the two groups was statistically significant (P<0.001). Large tumors accounted for 46.2% (138/299) vs 77.1% (108/140) in the surgery group and radiotherapy group. The difference between the two groups was statistically significant (P<0.001). Further stratified analysis, a total of 46 patients with large tumors of FIGO 2009 stage Ⅱb in the radiotherapy group were extracted, and the survival rate was 67.4%, there was no significant difference compared with the surgery group (81.2%; P=0.052). ③ Of 126 patients with common iliac lymph node, 83 patients survived, with a survival rate of 65.9% (83/126). In the surgery group, 48 patients survived and 17 died, with a survival rate of 73.8%. In the radiotherapy group, 35 patients survived and 26 died, with a survival rate of 57.4%. There were no significant difference between the two groups (P=0.051). (3) Side effects: the incidence of lymphocysts and intestinal obstruction in the surgery group were higher than those in the radiotherapy group, and the incidence of ureteral obstruction and acute and chronic radiation enteritis were lower than those in the radiotherapy group, and there were statistically significant differences (all P<0.01). Conclusions: For stage Ⅲc1 patients who meet the conditions for surgery, surgery combined with postoperative adjuvant chemoradiotherapy and radical chemoradiotherapy are acceptable treatment methods regardless of pelvic lymph node metastasis (excluding common iliac lymph node metastasis), even if the maximum diameter of the tumor is ≥4 cm. For patients with common iliac lymph node metastasis and stage Ⅲc2, there is no significant difference in the survival rate between the two treatment methods. Based on the duration of treatment and economic considerations, concurrent chemoradiotherapy is recommended for the patients.

Uterine choriocarcinoma coexistence with endometroid adenocacinoma: a case report and literature review

BackgroundChoriocarcinoma coexisting with endometrial carcinoma is rare. To the best of our knowledge, only one case of choriocarcinoma coexisting with endometrial carcinoma has been reported.Case presentationHere, we present this case and provide a literature review. A 38-year-old unmarried nulliparous woman presented to the clinic with a menstrual disorder for more than 3 months. She then underwent a hysteroscopic procedure. The pathological findings were malignant, two types of carcinoma, and no transitional lesions were observed; about 85% of them were choriocarcinoma with smooth muscle infiltration and intravascular investigation of the thrombus; about 15% were highly differentiated endometrioid adenocarcinoma; Immunohistochemistry (endometrioid/choriocarcinoma): Vim (+ + / + + +), P40 (+ ±), CK5/6 multifocal ( ±), CK7 ( ±), EMA (+ ±), P16 multifocal ( ±), P53 (+ / + +), WT-1 (-/ + +), hCG (-/ + + +), CD138 (-/ + + +), Gly-3 (-/-), ER ( ±), PR (+ ±), Sall-4 (-/-), P21 (-/ +), P27 (-/ + + +), CyclinE (-/ + +), Ki67 positivity rate (10%/95%). We performed a laparoscopic hysterectomy, bilateral adnexectomy, and pelvic and para-abdominal lymph node dissection after five cycles of chemotherapy. She was diagnosed with choriocarcinoma with endometrial cancer, stage IVb choriocarcinoma and stage IA endometrial cancer. Postoperative radiochemotherapy was administered. The patient was disease-free 40 months after the treatment ended.ConclusionWe report a case of choriocarcinoma coexisting with endometrial carcinoma and provide a literature review that may help inspire additional studies in the future.

Genetic polymorphisms in genes regulating cell death and prognosis of patients with rectal cancer receiving postoperative chemoradiotherapy.

The identification of biomarkers for predicting chemoradiotherapy efficacy is essential to optimize personalized treatment. This study determined the effects of genetic variations in genes involved in apoptosis, pyroptosis, and ferroptosis on the prognosis of patients with locally advanced rectal cancer receiving postoperative chemoradiotherapy (CRT). The Sequenom MassARRAY was used to detect 217 genetic variations in 40 genes from 300 patients with rectal cancer who received postoperative CRT. The associations between genetic variations and overall survival (OS) were evaluated using hazard ratios (HRs) and 95% confidence intervals (CIs) computed using a Cox proportional regression model. Functional experiments were performed to determine the functions of the arachidonate 5-lipoxygenase (ALOX5) gene and the ALOX5 rs702365 variant. We detected 16 genetic polymorphisms in CASP3, CASP7, TRAILR2, GSDME, CASP4, HO-1, ALOX5, GPX4, and NRF2 that were significantly associated with OS in the additive model (P < 0.05). There was a substantial cumulative effect of three genetic polymorphisms (CASP4 rs571407, ALOX5 rs2242332, and HO-1 rs17883419) on OS. Genetic variations in the CASP4 and ALOX5 gene haplotypes were associated with a higher OS. We demonstrated, for the first time, that rs702365 [G] > [C] represses ALOX5 transcription and corollary experiments suggested that ALOX5 may promote colon cancer cell growth by mediating an inflammatory response. Polymorphisms in genes regulating cell death may play essential roles in the prognosis of patients with rectal cancer who are treated with postoperative CRT and may serve as potential genetic biomarkers for individualized treatment.