The Use of Trimodality Treatment in Patients With Locally Advanced Oesophageal Squamous Cell Carcinoma: An Experience From a Large Cancer Centre in Pakistan.

Introduction Esophageal cancer is one of the most common cancers worldwide. Neoadjuvant chemoradiotherapy followed by surgery is the standard treatment for locally advanced squamous cell carcinoma (SCC). Pathological complete response (pCR) after surgery is associated with better outcomes in terms of overall survival and disease-free survival. We aim to determine the effectiveness of neoadjuvant chemoradiotherapy in patients with locally advanced SCC at our institute, the largest purpose-built cancer center in Pakistan. We also aim to identify various factors influencing pCR, such as chemotherapy regimen, total radiation dose, clinical stage at presentation, and gender. Materials and methods This is a retrospective review of all patients with esophageal SCC presented between January 2019 and 2021 to the institute for treatment. Patients received neoadjuvant chemoradiotherapy (nCRT) as per the CROSS trial protocol, followed by surgery. We assessed the pCR rate. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York). pCR was studied alongside associated factors such as age, gender, stage of disease, chemotherapy regimen, and total dose of radiotherapy. A p-value of <0.05 was considered statistically significant. The chi-square test was used to compare categorical variables. Univariate and multivariate logistic regression was employed to evaluate factors affecting pCR. Results A total of 218 patients were included in the study. pCR was achieved in 64.2% of the patients. The female gender was associated with better outcomes, as 70.4% (n=81) of female patients achieved a complete pathological response, compared to 57.3% (n=59) of males, with a p-value of 0.03. On univariate analysis, the complete pathological response was 69.6% (n=94) in the age group of 45 years and below, whereas it was 55.4% (n=46) in the age group above 45 years, with a p-value of 0.024. Though statistically insignificant, outcomes were slightly better for those with node-negative disease, as 67.2% (n=41) achieved complete pathological response compared to those with node-positive disease at 63.1% (n=99). Univariate logistic regression analysis identified gender (p=0.044, OR=1.77, 95% CI: 1.016-3.108) and age group (p=0.034, OR=1.844, 95% CI: 1.046-3.252) as significantly associated with pCR. Female patients were 77% more likely to achieve pCR compared to male patients (OR=1.77, 95% CI: 1.016-3.108). Younger patients (≤45 years) were 84.4% more likely to achieve pCR compared to the older age group (OR=1.844, 95% CI: 1.046-3.252). However, these did not maintain significance in multivariate logistic regression analysis. Conclusion Our study indicated a high rate of pCR with nCRT in patients with esophageal SCC compared to other studies. The achievement of pCR was higher among females and younger patients, which was statistically significant on univariate logistic regression analysis. Our study also concluded that a higher dose of RT (50Gy/25#) is not superior to a lower dose (45Gy/25#) in terms of pCR achievement but was statistically insignificant. Similarly, CARBO/PAC was not superior to CIS/CAP in terms of pCR achievement and was also statistically insignificant.

Radiotherapy Versus Chemotherapy in Locally Advanced Cervical Cancer.

Eighty percent of women who have cervical cancer present at such an alarmingly advanced stage leading to high morbidity and mortality. Due to a lack of public awareness and inadequate infrastructure for screening and early identification in resource-poor countries like India, this tardy presentation is anticipated to continue in the future. Standard management for locally advanced squamous cell cervical cancer is radiotherapy. To increase responses and survival, neoadjuvant chemotherapy (NACT) was introduced to the arsenal. Recent studies from India have shown encouraging results for women getting concomitant chemo-radiation for locally advanced cervical cancer. However, toxicities are still a major problem. The approximated five-year actuarial survival rate with NACT is roughly 45% (95% confidence interval, 37-53%) with a median survival rate of 56 months. Compared to radiotherapy alone, patients receiving chemo-radiation are said to have a considerably better survival rate. Vomiting and nausea are the adverse effects that occur most frequently. Renal dysfunction and myelosuppression can also happen. However, there is evidence of effective tumor control. We will talk about a 55-year-old, para 5 elderly lady who had white discharge coming from her vagina and a cervical mass that bled when touched. She underwent NACT for six weekly cycles, followed by definitive chemo-radiation, and she responded favorably to this management strategy, indicating that the addition of chemotherapy is yet another cause for optimism in the management of cancer of the cervix.

Optimized decision support for selection of transoral robotic surgery or (chemo)radiation therapy based on posttreatment swallowing toxicity.

BACKGROUND: A primary goal in transoral robotic surgery (TORS) for oropharyngeal squamous cell cancer (OPSCC) survivors is to optimize swallowing function. However, the uncertainty in the outcomes of TORS including postoperative residual positive margin (PM) and extranodal extension (ENE), may necessitate adjuvant therapy, which may cause significant swallowing toxicity to survivors. METHODS: A secondary analysis was performed on a prospective registry data with low- to intermediate-risk human papillomavirus-related OPSCC possibly resectable by TORS. Decision trees were developed to model the uncertainties in TORS compared with definitive radiation therapy (RT) and chemoradiation therapy (CRT). Swallowing toxicities were measured by Dynamic Imaging Grade of Swallowing Toxicity (DIGEST), MD Anderson Dysphagia Inventory (MDADI), and the MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) instruments. The likelihoods of PM/ENE were varied to determine the thresholds within which each therapy remains optimal. RESULTS: Compared with RT, TORS resulted in inferior swallowing function for moderate likelihoods of PM/ENE (>60% in short term for all instruments, >75% in long term for DIGEST and MDASI) leaving RT as the optimal treatment. Compared with CRT, TORS remained the optimal therapy based on MDADI and MDASI but showed inferior swallowing outcomes based on DIGEST for moderate-to-high likelihoods of PM/ENE (>75% for short-term and >40% for long-term outcomes). CONCLUSION: In the absence of reliable estimation of postoperative PM/ENE concurrent with significant postoperative PM, the overall toxicity level in OPSCC patients undergoing TORS with adjuvant therapy may become more severe compared with patients receiving nonsurgical treatments thus advocating definitive (C)RT protocols.

The Multidisciplinary Approach in Stage III Non-Small Cell Lung Cancer over Ten Years: From Radiation Therapy Optimisation to Innovative Systemic Treatments.

Background: About 30% of new non-small cell lung cancer (NSCLC) cases are diagnosed at a locally advanced stage, which includes a highly heterogeneous group of patients with a wide spectrum of treatment options. The management of stage III NSCLC involves a multidisciplinary team, adequate staging, and a careful patient selection for surgery or radiation therapy integrated with systemic treatment. Methods: This is a single-center observational retrospective and prospective study including a consecutive series of stage III NSCLC patients who were referred to the Veneto Institute of Oncology and University Hospital of Padova (Italy) between 2012 and 2021. We described clinico-pathological characteristics, therapeutic pathways, and treatment responses in terms of radiological response in the entire study population and in terms of pathological response in patients who underwent surgery after induction therapy. Furthermore, we analysed survival outcomes in terms of relapse-free survival (RFS) and overall survival (OS). Results: A total of 301 patients were included. The majority of patients received surgical multimodality treatment (n = 223, 74.1%), while the remaining patients (n = 78, 25.9%) underwent definitive CRT followed or not by durvalumab as consolidation therapy. At data cut-off, 188 patients (62.5%) relapsed and the median RFS (mRFS) of the entire population was 18.2 months (95% CI: 15.83−20.57). At the time of analyses 140 patients (46.5%) were alive and the median OS (mOS) was 44.7 months (95% CI: 38.4−51.0). A statistically significant difference both in mRFS (p = 0.002) and in mOS (p < 0.001) was observed according to the therapeutic pathway in the entire population, and selecting patients treated after 2018, a significant difference in mRFS (p = 0.006) and mOS (p < 0.001) was observed according to treatment modality. Furthermore, considering only patients diagnosed with stage IIIB-C (N = 131, 43.5%), there were significant differences both in mRFS (p = 0.047) and in mOS (p = 0.022) as per the treatment algorithm. The mRFS of the unresectable population was 16.3 months (95% CI: 11.48−21.12), with a significant difference among subgroups (p = 0.030) in favour of patients who underwent the PACIFIC-regimen; while the mOS was 46.5 months (95% CI: 26.46−66.65), with a significant difference between two subgroups (p = 0.003) in favour of consolidation immunotherapy. Conclusions: Our work provides insights into the management and the survival outcomes of stage III NSCLC over about 10 years. We found that the choice of radical treatment impacts on outcome, thus suggesting the importance of appropriate staging at diagnosis, patient selection, and of the multidisciplinary approach in the decision-making process. Our results confirmed that the PACIFIC trial and the following introduction of durvalumab as consolidation treatment may be considered as a turning point for several improvements in the diagnostic-therapeutic pathway of stage III NSCLC patients.

Deep neural networks for neuro-oncology: Towards patient individualized design of chemo-radiation therapy for Glioblastoma patients.

BACKGROUND AND OBJECTIVES: Glioblastoma multiforme (GBM) is the most common and deadly type of primary cancers of the brain and central nervous system in adults. Despite the importance of designing a personalized treatment regimen for the patient, clinical trials prescribe a set of conventional regimens for GBM patients. We propose a computerized framework for designing chemo-radiation therapy (CRT) regimen based on patient characteristics. METHODS: An intelligent agent, based on deep reinforcement learning, interacts with a virtual personalized GBM. The proposed deep Q network (DQN) uses a deep neural network to estimate the state - action value function. The algorithm stores agent experiences in a replay memory to be used for training of the deep neural network. Also, the proliferation-invasion model is used to simulate spatiotemporal dynamics of GBM growth and its response to therapeutic agents. RESULTS: Assuming tumor size at the end of the treatment course as a measure of the quality of the treatment regimen, experiments show that the proposed DQN is superior to the Q learning. Also, while the quality of the protocols obtained by the Q learning as well as its convergence speed decreases sharply with the increase in the dimensions of the state-action value function, the DQN is relatively robust against increasing the initial tumor size or lengthening the treatment period. CONCLUSION: Our results suggest that the optimal personalized treatment regimen may differ from the conventional regimens suggested by clinical trials. Given the scalability of the proposed DQN in designing treatment regimen for real size tumors, as well as its superiority over previous models, it is a suitable tool for designing personalized CRT regimen for GBM patients.

Pancreatic cancer derived 3D organoids as a clinical tool to evaluate the treatment response.

Background and purpose: Pancreatic cancer (PC) is the fourth leading cause of cancer death in both men and women. The standard of care for patients with locally advanced PC of chemotherapy, stereotactic radiotherapy (RT), or chemo-radiation-therapy has shown highly variable and limited success rates. However, three-dimensional (3D) Pancreatic tumor organoids (PTOs) have shown promise to study tumor response to drugs, and emerging treatments under in vitro conditions. We investigated the potential for using 3D organoids to evaluate the precise radiation and drug dose responses of in vivo PC tumors. Methods: PTOs were created from mouse pancreatic tumor tissues, and their microenvironment was compared to that of in vivo tumors using immunohistochemical and immunofluorescence staining. The organoids and in vivo PC tumors were treated with fractionated X-ray RT, 3-bromopyruvate (3BP) anti-tumor drug, and combination of 3BP + fractionated RT. Results: Pancreatic tumor organoids (PTOs) exhibited a similar fibrotic microenvironment and molecular response (as seen by apoptosis biomarker expression) as in vivo tumors. Untreated tumor organoids and in vivo tumor both exhibited proliferative growth of 6 folds the original size after 10 days, whereas no growth was seen for organoids and in vivo tumors treated with 8 (Gray) Gy of fractionated RT. Tumor organoids showed reduced growth rates of 3.2x and 1.8x when treated with 4 and 6 Gy fractionated RT, respectively. Interestingly, combination of 100 µM of 3BP + 4 Gy of RT showed pronounced growth inhibition as compared to 3-BP alone or 4 Gy of radiation alone. Further, positive identification of SOX2, SOX10 and TGFß indicated presence of cancer stem cells in tumor organoids which might have some role in resistance to therapies in pancreatic cancer. Conclusions: PTOs produced a similar microenvironment and exhibited similar growth characteristics as in vivo tumors following treatment, indicating their potential for predicting in vivo tumor sensitivity and response to RT and combined chemo-RT treatments.

A Case of Hypopharyngeal Cancer Associated With Fanconi Anemia: A Helical Tomotherapy Experience.

Fanconi anemia (FA) is a disease that could be accompanied by multiple abnormalities, such as growth retardation, bone marrow abnormalities, and cancer susceptibility. Among the FA patients, head and neck squamous cell cancer (HNSCC) is the most observed solid cancer. The life expectancy of patients with FA has increased with recent medical advances. Furthermore, HNSCC is diagnosed in 3% of FA patients, and half of these patients die because of their HNSCC. The median age of HNSCC patients with FA is 31, and according to the literature HNSCC incidence of FA, patients is more than 700-fold of the normal population. Here, we reported the treatment details and challenges we faced during hypopharyngeal cancer treatment in a FA patient.

Covered metallic stent placement for biliary drainage could be promising in the coming era of neoadjuvant chemo-radiation therapy for all pancreatic cancer.

BACKGROUND/PURPOSE: The role of endoscopic preoperative biliary drainage for pancreatic head cancer is controversial because of the high incidence of stent occlusion before surgery. We sought to validate a suitable stent for biliary drainage in patients with pancreatic cancer undergoing neoadjuvant chemotherapy (NAC)/neoadjuvant chemoradiotherapy (NAC-RT). METHODS: We evaluated patients who received preoperative neoadjuvant therapy for pancreatic head cancer between January 2013 and December 2019. A covered metal (CMS) or plastic stent (PS) was inserted in symptomatic patients for biliary drainage. Recurrent biliary obstruction (RBO), success rate of endoscopic drainage, adverse events, and surgical outcomes were compared between the CMS and PS groups. RESULTS: Occurrence rate of RBO was significantly higher with PS (97%) vs CMS (15%, P < .001), and time to RBO was significantly longer with CMS vs PS (not reached vs 40.5 days, P < .001). Delayed schedule associated with RBO for neoadjuvant chemotherapy was significantly lower in CMS vs PS (14% vs 50%, P < .05). There was no difference in postoperative bleeding, operation time, complications, and rate of a microscopically margin-negative resection between groups. CONCLUSIONS: Use of CMS during NAC/NAC-RT allows for safe chemotherapy without causing cholangitis or biliary obstruction and for surgery to be performed.

Redefining Role of 5-Fluorouracil and Exploring the Impact of Taxanes and Cisplatin in Locally Advanced and Recurrent Carcinoma Cervix in Concurrent Setting With Radiotherapy: A Literature Review.

Cervical carcinoma is the fourth most frequent cancer among women worldwide while it is common in rural India. The irony of the situation is that it continues to present in a locally advanced stage with bulky disease posing a significant challenge to the current treatment modalities despite various screening programs. Concurrent chemoradiotherapy is the mainstay of treatment for locally advanced carcinoma cervix. However, the appropriate dosing schedules, along with the salutation of the chemotherapeutic agent, remain a matter of debate to date. The use of chemotherapy in the neoadjuvant and adjuvant setting promises to improve progression-free survival and overall survival. The article aims to review various chemotherapy and their regimens in the treatment of carcinoma of the cervix.

Sarcopenia in male patients with head and neck cancer receiving chemoradiotherapy: a longitudinal pilot study.

INTRODUCTION: Muscle wasting conditions such as sarcopenia may be highly prevalent in advanced head and neck cancer (HNC) patients (16-71%), with these prevalence rates substantially greater in those who have received chemo-radiotherapy (CRT). According to the updated European Working Group on Sarcopenia in Older People consensus statement, sarcopenia is defined as the age-related loss of muscle strength, muscle mass and physical performance. The high prevalence of sarcopenia in HNC patients is concerning as it has been associated with substantially increased risk of CRT toxicity, respiratory complications and early mortality. With the high prevalence of HNC and sarcopenia in India and the strong link between sarcopenia and poor HNC patient outcomes, it is important to screen for the presence of sarcopenia in Indian patients receiving CRT for HNC. METHODS: This longitudinal pilot study aimed to routinely monitor 19 men receiving CRT for their HNC for a variety of sarcopenic-related outcomes over three time points during their 7 weeks of CRT. Participants were required to be male, with a minimum age of 30 years, with a Stage III, IVa or IVb diagnosis of HNC and be currently undergoing a 7 weeks course of CRT in an oncology department. Outcomes included probable sarcopenic diagnosis were estimated by the SARC-F, handgrip strength, skeletal muscle mass was estimated by bioelectrical impedance and physical performance was assessed by the Timed Up and Go. Repeated measures ANOVA and Bonferroni post-hoc tests were used to identify significant differences at the three time points with a p < 0.05. RESULTS: The 19 participants in this trial at a mean age of 56.5 ± 10.2 years (range = 39-75 years), with most (n = 13, 68.4%) employed in laboring occupations. At baseline, 31.5% (n = 6) of the participants already had probable sarcopenia based on their total SARC-F score, with this increasing to 89.4% (n = 17) at the end of 7 weeks CRT. In addition, significant decreases in strength, skeletal muscle mass and Timed Up and Go performance were observed, with these declines significantly greater at 7 weeks than 3 weeks after commencing CRT. CONCLUSIONS: Patients with HNC undergoing 7 weeks of CRT showed clinically significant increases in the incidence of probable sarcopenia based on their total SARC-F score as well as clinically significant declines in handgrip strength, skeletal muscle mass and Timed Up and Go performance. Due to the relationship between sarcopenia and a host of adverse events related to CRT in HNC patients, these results suggest that oncologists and their allied health teams should routinely monitor these patients during CRT and provide the relevant exercise therapy and nutritional support to those patients in need.

Cytokine gene variants and treatment outcome of cisplatin-based concomitant chemoradiotherapy in cervical cancer.

Background: Cervical cancer is the second most common cancer among women after breast cancer. Its standard treatment is cisplatin-based concomitant chemoradiotherapy. Chronic inflammation in uterine cervix triggers both pro- and anti-inflammatory pathways. The unpredictability in toxicity and efficacy of treatment is a major challenge. We hypothesized a link between IL-1, IL-6 and TNF gene variants and treatment response.Material & Methods: We genotyped 246 cervical cancer cases and 246 controls by PCR, PCR-RFLP and ARMS-PCR. Treatment and response were evaluated by RECIST criteria. Chemotherapy and radiation doses were same for all patients, whilst 48 were followed-up for 36 months after treatment.Results: SNPs in IL-1RN, IL-1ß, IL-6 and TNFα were linked with cervical cancer. Cases with certain allele combinations in IL-1RN, IL-1ß, IL-6(-597A/G) and TNF-α showed odds ratios (95% CI) of up to 17.54 (2.7-24.08) for the presence of cervical cancer. Variant IL-1ß (-511T/C) was linked to vital status but none were linked to overall survival.Conclusion: Certain cytokine gene variants may help detect susceptibility to cervical cancer and predict response to chemoradiotherapy.

Recent Advances in Head and Neck Tumor Microenvironment-Based Therapy.

Head and neck squamous cell carcinomas (HNSCCs) are a group of heterogeneous aggressive tumors affecting more than half a million patients worldwide annually. While the tobacco- and alcohol-associated HNSCC tumors are declining, human papillomavirus (HPV)-induced tumors are on rise. Despite recent advances in multimodality therapeutic interventions including surgery in combination with chemoradiation therapy (CRT), the overall 5-year survival has not improved more than 50%. The underlying reasons for this dismal prognosis is the intrinsic or acquired resistance to CRT. While previous studies were focused to target tumor cells, recent findings have implicated the involvement of tumor microenvironment (TME) on tumor progression and response to therapy. HNSCC TME includes cancer-associated fibroblasts (CAFs), endothelial cells, immune cells, endocrine cells, and the extracellular matrix (ECM) proteins including collagen and fibronectin. Understanding the crosstalk between TME and cancer cells is important to formulate more effective novel therapies and to overcome resistance mechanisms. Here, we summarized the current literature on recent advances on HNSCC TME with special emphasis on novel cell-cell interactions and therapies currently under development.

Neoadjuvant chemo-radiotherapy for cT3N0 rectal cancer: any benefit over upfront surgery? A propensity score-matched study.

PURPOSE: Benefits of neoadjuvant chemo-radiotherapy (CRT) are well known for locally advanced and/or node-positive rectal cancer, but the best timing for CRT has been less explored for cT3N0 patients. The aim of the present study was to compare the 5-year disease-free survival (DFS) probability between neoadjuvant CRT and upfront surgery in patients affected by cT3N0 rectal cancer. METHODS: A retrospective review of 105 patients affected by cT3N0 rectal cancer, staged by pelvic magnetic resonance imaging and treated at the National Cancer Institute of Milan between 2011 and 2017, was performed: 42 (40.0%) were treated by neoadjuvant CRT and 63 (60.0%) by upfront surgery. Propensity score matching was performed to avoid selection bias, and Cox multivariate regression was used to analyze outcomes. RESULTS: The 5-year DFS probability was 87.5% in neoadjuvant CRT patients vs. 90.0% in upfront surgery cases (Log-rank p = 0.76). The 5-year loco-regional recurrence-free survival probability was respectively 96.8% vs. 96.3% (Log-rank p = 0.954). On multivariate analysis, neoadjuvant CRT had no impact on DFS when compared to upfront surgery (adjusted HR 0.71, 95%CI 0.18-2.70, p = 0.613), but 61.9% of upfront surgery cases were treated by adjuvant chemo-radiation (adjusted HR 0.41, 95%CI 0.11-1.57, p = 0.196). The only independent predictor of improved DFS was age at diagnosis (adjusted HR 0.95, p = 0.017). CONCLUSION: CRT should be considered for cT3N0 patients, but its timing (neoadjuvant vs. adjuvant) seems not to affect the disease-free survival in the present cohort of patients.

Salvage Concurrent Chemo-radiation Therapy for Loco-regional Recurrence Following Curative Surgery of Non-small Cell Lung Cancer.

PURPOSE: This study is to report clinical outcomes of salvage concurrent chemo-radiation therapy (CCRT) in treating patients with loco-regional recurrence (LRR) following initial complete resection of non-small cell lung cancer. MATERIALS AND METHODS: Between February 2004 and December 2016, 127 patients underwent salvage CCRT for LRR. The median radiation therapy (RT) dose was 66 Gy and clinical target volume was to cover recurrent lesion with margin without elective inclusion of regional lymphatics. Majority of patients (94.5%) received weekly platinum-based doublet chemotherapy during RT course. RESULTS: The median follow-up time from the start of CCRT was 25 months. The median survival duration was 49 months, and overall survival (OS) rates at 2 and 5 years were 72.9% and 43.9%. The 2- and 5-year rates of in-field failure-free survival, distant metastasis free survival, and progression free survival were 82.4% and 73.8%, 50.4% and 39.9%, and 34.6% and 22.3%, respectively. Grade ≥ 3 radiation-related esophagitis and pneumonitis occurred in 14 (11.0%) and six patients (4.7%), respectively. On both univariate and multivariate analysis, higher biologically equivalent dose (BED10) (≥ 79.2 Gy10 vs. < 79.2 Gy10; hazard ratio [HR], 0.431), smaller CTV (≤ 80 cm3 vs. > 80 cm3; HR, 0.403), and longer disease-free interval (> 1 year vs. ≤ 1 year; HR, 0.489) were significantly favorable factors for OS. CONCLUSION: The current study has demonstrated that high dose salvage CCRT focused to the involved lesion only was highly effective and safe. In particular, higher BED10, smaller CTV, and longer disease-free interval were favorable factors for improved survival.

Improving Treatment Response Prediction for Chemoradiation Therapy of Pancreatic Cancer Using a Combination of Delta-Radiomics and the Clinical Biomarker CA19-9.

Recently we showed that delta radiomics features (DRF) from daily CT-guided chemoradiation therapy (CRT) is associated with early prediction of treatment response for pancreatic cancer. CA19-9 is a widely used clinical biomarker for pancreatic cancer. The purpose of this work is to investigate if the predictive power of such biomarkers (DRF or CA19-9) can improve by combining both biomarkers. Daily non-contrast CTs acquired during routine CT-guided neoadjuvant CRT for 24 patients (672 datasets, in 28 daily fractions), along with their CA19-9, pathology reports and follow-up data were analyzed. The pancreatic head was segmented on each daily CT and radiomic features were extracted from the segmented regions. The time between the end of treatment and last follow-up was used to build a survival model. Patients were divided into two groups based on their pathological response. Spearman correlations were used to find the DRFs correlated to CA19-9. A regression model was built to examine the effect of combining CA19-9 and DRFs on response prediction. C-index was used to measure model effectiveness. The effect of a decrease in CA19-9 levels during treatment vs. failure of CA19-9 levels to normalize on survival was examined. Univariate- and multivariate Cox-regression analysis were performed to determine the effect of combining CA19-9 and DRFs on survival correlations. Spearman correlation showed that CA19-9 is correlated to DRFs (Entropy, cluster tendency and coarseness). An Increase in CA19-9 levels during treatment were correlated to a bad response, while a decline was correlated to a good response. Incorporating CA19-9 with DRFs increased the c-index from 0.57 to 0.87 indicating a stronger model. The univariate analysis showed that patients with decreasing CA19-9 had an improved median survival (68 months) compared to those with increasing levels (33 months). The 5-years survival was improved for the decreasing CA19-9 group (55%) compared to the increasing group (30%). The Cox-multivariate analysis showed that treatment related decrease in CA19-9 levels (p = 0.031) and DRFs (p = 0.001) were predictors of survival. The hazard-ratio was reduced from 0.73, p = 0.032 using CA19-9 only to 0.58, p = 0.028 combining DRFs with CA19-9. DRFs-CA19-9 combination has the potential to increasing the possibility for response-based treatment adaptation.

Salvage Concurrent Chemo-radiation Therapy for Loco-regional Recurrence Following Curative Surgery of Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study is to report clinical outcomes of salvage concurrent chemo-radiation therapy (CCRT) in treating patients with loco-regional recurrence (LRR) following initial complete resection of non-small cell lung cancer. MATERIALS AND METHODS: Between February 2004 and December 2016, 127 patients underwent salvage CCRT for LRR. The median radiation therapy (RT) dose was 66 Gy and clinical target volume was to cover recurrent lesion with margin without elective inclusion of regional lymphatics. Majority of patients (94.5%) received weekly platinum-based doublet chemotherapy during RT course. RESULTS: The median follow-up time from the start of CCRT was 25 months. The median survival duration was 49 months, and overall survival (OS) rates at 2 and 5 years were 72.9% and 43.9%. The 2- and 5-year rates of in-field failure-free survival, distant metastasis free survival, and progression free survival were 82.4% and 73.8%, 50.4% and 39.9%, and 34.6% and 22.3%, respectively. Grade ≥ 3 radiation-related esophagitis and pneumonitis occurred in 14 (11.0%) and six patients (4.7%), respectively. On both univariate and multivariate analysis, higher biologically equivalent dose (BED₁₀) (≥ 79.2 Gy₁₀ vs. 80 cm³; HR, 0.403), and longer disease-free interval (> 1 year vs. ≤ 1 year; HR, 0.489) were significantly favorable factors for OS. CONCLUSION: The current study has demonstrated that high dose salvage CCRT focused to the involved lesion only was highly effective and safe. In particular, higher BED₁₀, smaller CTV, and longer disease-free interval were favorable factors for improved survival.

Results of a pooled analysis of IOERT containing multimodality treatment for locally recurrent rectal cancer: Results of 565 patients of two major treatment centres.

OBJECTIVE: Aim of this study is analysing the pooled results of Intra-Operative Electron beam Radiotherapy (IOERT) containing multimodality treatment of locally recurrent rectal cancer (LRRC) of two major treatment centres. METHODS AND MATERIALS: Five hundred sixty five patients with LRRC who underwent multimodality-treatment up to 2010 were studied. The preferred treatment was preoperative chemo-radiotherapy, surgery and IOERT. In uni- and multivariate analyses risk factors for local re-recurrence, distant metastasis free survival, relapse free survival, cancer-specific survival and overall survival were studied. RESULTS: Two hundred fifty one patients (44%) underwent a radical (R0) resection. In patients who had no preoperative treatment the R0 resection rate was 26%, and this was 43% and 50% for patients who respectively received preoperative re-(chemo)-irradiation or full-course radiotherapy (p < 0.0001). After uni- and multivariate analysis it was found that all oncologic parameters were influenced by preoperative treatment and radicality of the resection. Patients who were re-irradiated had a similar outcome compared to patients, who were radiotherapy naive and could undergo full-course treatment, except the chance of local re-recurrence was higher for re-irradiated patients. Waiting-time between preoperative radiotherapy and IOERT was inversely correlated with the chance of local re-recurrence, and positively correlated with the chance of a R0 resection. CONCLUSIONS: R0 resection is the most important factor influencing oncologic parameters in treatment of LRRC. Preoperative (chemo)-radiotherapy increases the chance of achieving radical resections and improves oncologic outcomes. Short waiting-times between preoperative treatment and IOERT improves the effectiveness of IOERT to reduce the chance of a local re-recurrence.

Usefulness of chemoradiotherapy for inoperable gastric cancer.

Introduction Radiotherapy is not commonly used for the treatment of gastric cancer in Japan, where surgery is the standard local treatment. We report the results of chemoradiotherapy in patients with advanced or recurrent gastric cancer which was deemed difficult to treat surgically. Methods Twenty-one patients with gastric cancer (including sixteen with advanced/recurrent gastric cancer and five with poor general condition) underwent chemo-radiotherapy, for whom the therapeutic efficacy, toxicity and survival period were analysed. Results The tumour response to chemoradiotherapy was categorised as complete, partial, stable or progressive in 5, 9, 3, and 4 patients, respectively, with an overall response rate of 67%. No serious complications such as gastrointestinal perforation or bleeding occurred, and no cardiac, hepatic or renal dysfunction developed during the follow-up period. The mean survival time was 19.8 months (range, 3-51 months). One patient died of another disease, 18 died of primary cancer and the cause of death was unknown in 2 patients. Conclusions Chemoradiotherapy appears to be an effective treatment for localised gastric cancer without distant metastases, but further studies are needed to determine the indications for chemoradiotherapy and late adverse effects, as well as the chemotherapy regimens to be used.

Circulating tumor cells: A promising marker of predicting tumor response in rectal cancer patients receiving neoadjuvant chemo-radiation therapy.

PURPOSE: The aim of this study was to investigate the role of circulating tumor cells (CTCs) in assessing and predicting tumor response to neoadjuvant chemoradiotherapy (CRT) for patients with locally advanced rectal cancer (LARC). METHODS: A total of 115 patients with T3-4 and/or N+ rectal cancer were enrolled. All patients received neoadjuvant CRT followed by radical surgery after 6-8 weeks. The pathological results after surgery were evaluated according to tumor regression grade (TRG) classification. RESULTS: Based on TRG score, patients were classified as responders (TRG3-4) and non-responders (TRG0-2). The baseline CTC counts of responders were significantly higher than those of non-responders (44.50±11.94 vs. 37.67±15.45, P=0.012). By contrast, the post-CRT CTC counts of responders were significantly lower than those of non-responders (3.61±2.90 vs. 12.08±7.40, P<0.001). According to ROC analysis, Δ%CTC (percentage difference in CTC counts between baseline and post-CRT) was identified as the stronger predictor to discriminate responders from non-responders (AUC: 0.860). The results of multivariate analysis also indicated that post-CRT CTC counts and Δ%CTC were significantly and independently associated with tumor response to CRT. CONCLUSIONS: The detection of CTCs is a powerful and promising tool for evaluating and predicting responses to neoadjuvant CRT in LARC patients.

Human papillomavirus in oropharyngeal cancer: The changing face of a disease.

The last decade has brought about an unexpected rise in oropharyngeal squamous cell carcinoma (OPSCC) primarily in white males from the ages of 40-55years, with limited exposure to alcohol and tobacco. This subset of squamous cell carcinoma (SCC) has been found to be associated with human papillomavirus infection (HPV). Other Head and Neck Squamous Cell carcinoma (HNSCC) subtypes include oral cavity, hypopharyngeal, nasopharyngeal, and laryngeal SCC which tend to be HPV negative. HPV associated oropharyngeal cancer has proven to differ from alcohol and tobacco associated oropharyngeal carcinoma in regards to the molecular pathophysiology, presentation, epidemiology, prognosis, and improved response to chemoradiation therapy. Given the improved survival of patients with HPV associated SCC, efforts to de-intensify treatment to decrease treatment related morbidity are at the forefront of clinical research. This review will focus on the important differences between HPV and tobacco related oropharyngeal cancer. We will review the molecular pathogenesis of HPV related oropharyngeal cancer with an emphasis on new paradigms for screening and treating this disease.