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Highlights • IMRT is associated with favorable toxicity rates for patients with anal cancer. • Outcomes were favorable for those with T3-4 tumors or lymph node involvement. • Current smokers are at a higher risk of severe dermatologic toxicity. • Overall treatment duration greater than 39 days is associated with recurrence., Introduction To report long-term efficacy and adverse events (AEs) associated with intensity modulated radiotherapy (IMRT) for patients with anal canal squamous cell carcinoma (ASCC). Materials and methods This was a retrospective review of patients with ASCC who received curative-intent IMRT and concurrent chemotherapy (98%) between 2003 and 2019. Overall survival (OS), colostomy-free survival (CFS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The cumulative incidence of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. Acute and late AEs were recorded per National Cancer Institute Common Terminology Criteria for AEs. Results 127 patients were included. The median patient age was 63 years (interquartile range [IQR] 55–69) and 79% of patients were female. 33% of patients had T3-4 disease and 68% had clinically involved pelvic or inguinal lymph nodes (LNs). The median patient follow-up was 47 months (IQR: 28–89 months). The estimated 4-year OS, CFS, and PFS were 81% (95% confidence interval [CI]: 73%–89%), 77% (95% CI: 68%–86%), and 78% (95% CI: 70%–86%), respectively. The 4-year cumulative incidences of LR, LRR, and DM were 3% (95% CI: 1%–9%), 9% (95% CI: 5%–17%), and 10% (95% CI: 6%–18%), respectively. Overall treatment duration greater than 39 days was associated with an increased risk of LRR (Hazard Ratio [HR]: 5.2, 95% CI: 1.4–19.5, p = 0.015). The most common grade 3+ acute AEs included hematologic (31%), gastrointestinal (GI) (17%), dermatologic (16%), and pain (15%). Grade 3+ late AEs included: GI (3%), genitourinary (GU) (2%), and pain (1%). Current smokers were more likely to experience grade 3+ acute dermatologic toxicity compared to former or never smokers (34% vs. 7%, p

Highlights • Distribution of recurrent HNSCC in relation to radiotherapy volume was evaluated. • Both p16 positive and negative HNSCC recur in high-risk treatment volume. • This indicates potential failure of multimodality imaging to disclose significant disease. • A need for biomarkers other than p16 to predict radiosensitivity continues to exist., Background Locoregional recurrence remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC). Human papilloma virus (HPV)-associated HNSCCs generally have a good prognosis but may recur even after standard photon radiotherapy (RT). Another incentive in observing patterns of recurrence is increased use of highly conformal techniques such as proton therapy. We therefore studied geographic distribution of recurrent tumors in relation to the high-risk treatment volume in a cohort of patients with HNSCC receiving combined modality therapy. Methods Medical records of 508 patients diagnosed with HNSCC in 2010–2015 were reviewed. We identified a subgroup that had local and/or regional recurrence at hybrid positron emission tomography (PET)/computed tomography (CT) and/or magnetic resonance imaging (MRI). We adapted p16 as a surrogate marker for HPV-positivity and only patients with known p16 status were eligible for a detailed analysis where recurrent tumor was copied on the planning CT and the dose received by the recurrent tumor volume was determined using dose-volume histograms. Results Twenty-five patients who had received either cisplatin (n = 23) or cetuximab-enhanced (n = 2) RT were identified. 31 locoregional recurrent tumors were detected among 18 p16 negative and 7 p16 positive patients. Of recurrent tumors 14 (45%) were classified as in-field, 5 (16%) as marginal miss, and 12 (39%) as true miss. p16 positive patients had 4 in-field, 2 marginal, and 1 true miss. By contrast, p16 negative patients had 10 in-field, 3 marginal, and 11 true miss recurrences. Conclusions Both p16 positive and negative HNSCC recur in high-risk treatment volume despite the common view of high radiosensitivity of the former. Biomarkers predicting radioresistance should be characterized in p16 positive tumors before widely embarking on de-escalated CRT protocols. Another concern is how to decrease the number of true or marginal misses in p16 negative cases despite multimodality imaging-based target delineation.

Highlights • Liver metastasis of anal squamous cell carcinoma with a presented pseudocyst is very rare. • Some hepatic diseases such as infections, simple biliary cysts, and neoplasms demonstrate a cystic change of the liver. • Metastasis should be suspected when CT findings in patients with a history of gastrointestinal cancer show cystic changes involving the liver., Introduction Liver metastasis of an anal squamous cell carcinoma (SCC) with a pseudocyst is uncommon. There are many diseases which form hepatic cystic lesions and sometimes it is difficult to arrive at an accurate diagnosis. Presentation of case A 69-year-old woman visited our hospital with complaints of bloody stool and difficult defecation. A palpable mass in the anal canal was found on digital examination. The laboratory tests revealed anemia and raised levels of SCC antigen. On endoscopy a type 2 tumor was identified in the anal canal and biopsy revealed SCC. The patient was diagnosed with advanced anal SCC (cT2N1aM0, cStage IIIA) as a result of the examination and underwent chemoradiotherapy (CRT); unfortunately the tumor persisted after CRT. A salvage abdominoperineal resection with D2 and left lateral lymph node dissection was conducted. Histopathologically, the tumor was diagnosed as poorly differentiated SCC. She was readmitted for fever 3 weeks after surgery, and the abdominal CT showed multiple low density areas with enhancement at the edge of the liver, suggesting abscess or metastasis. The metastatic SCC was revealed by cytology of liver drainage and liver biopsy. Discussion Anal cancers are sometimes encountered however; a pseudo cystic presentation of a liver metastasis is very rare which makes it difficult to distinguish from other diseases. Conclusion We present a case of SCC in the anal canal with liver metastasis presenting as a hepatic pseudocyst.

Background Colorectal cancers are the second most common cancers overall and are the third deadliest cancers. Complete resection is the treatment of choice for rectal cancers and chemoradiotherapy (CRT) is strongly recommended in stage 2 and 3. Low anterior resection (LAR) is the most common procedure used, but it requires the use of stapler which might be very expensive as one study estimated the median cost of LAR inpatients to be over 13.000 USD. However, coloanal pull-through (PT) used to be the common procedure before introducing staplers in the twentieth century and can be less expensive, but with higher complication rates. Materials and methods This is a retrospective case-control study from patients’ records who underwent either LAR or PT for their rectal cancer in Syria. All patients had either stage 2 or 3 cancer and were treated by the same group of surgeons and received the same adjuvant and neoadjuvant CRT protocol. Patients from both groups had the same prognosis and stages. Results This study included 60 participants, of which, 30 had LAR and 30 had PT. They all had successful removal of the cancer and follow-ups were for 1 year after the surgery. There were no significant differences between the two procedures in post-operative leak, urinary retention, stricture, sexual function and recurrence (p > 0.05). However, post-operative incontinence was more frequent with PT (p = 0.027). Conclusion PT can be an acceptable substitute of LAR in low income settings despite having higher incidence of incontinence., Highlights • Low anterior resection (LAR) is the preferred surgery for rectal cancers. • Coloanal pull-through (PT) used to be preferred before LAR. • PT has higher complications rates, but it is much cheaper. • PT might have similar survival outcomes compared to LAR.

Highlights • Lung cancer is the leading cause of cancer mortality worldwide. • Gold standard chemoradiotherapy is not deliverable for the majority of patients. • Radiation-induced DNA damage repair is an actionable mechanism of radioresistance. • Careful trial design is essential to elicit maximum impact on therapeutic index. • CONCORDE is a platform study of novel drug/radiotherapy combinations in lung cancer., Lung cancer is the leading cause of cancer mortality worldwide and most patients are unsuitable for ‘gold standard’ treatment, which is concurrent chemoradiotherapy. CONCORDE is a platform study seeking to establish the toxicity profiles of multiple novel radiosensitisers targeting DNA repair proteins in patients treated with sequential chemoradiotherapy. Time-to-event continual reassessment will facilitate efficient dose-finding.

Highlights • MRI derived total 23Na concentration differs significantly in glioma subregions. • Total 23Na concentration could reflect IDH mutation status and tumor grade. • 23Na MRI yields potential non-invasive biomarkers for the treatment of gliomas., Purpose This prospective clinical trial investigated sodium (23Na) MRI at 7 Tesla (T) field strength as biomarker for tumor extent, isocitrate dehydrogenase (IDH) mutation and O6-methylguanine DNA methyltransferase (MGMT) promotor methylation in glioma patients. Methods 28 glioma patients underwent 23Na MRI on a 7T scanner (Siemens Healthcare, Erlangen, Germany) parallel to standard 3T MRI before chemoradiation. Areas of Gadolinium-contrast enhancement (gdce), non-enhancing T2-hyperintensity (regarded as edema), necrosis, and normal-appearing white matter (nawm) were segmented on 3T MRI imaging and were co-registered with the 23Na images. The median total 23Na concentrations of all areas were compared by pairwise t-tests. Furthermore, areas of gdce and edema were merged to yield the whole tumor area without necrosis. Subsequently, the difference in median of the 23Na concentration of this whole tumor area was compared between IDH-mutated and IDH wild-type gliomas as well as MGMT methylated and MGMT not-methylated glioblastomas using Whitney-Mann U-tests. All p-values were corrected after the Bonferroni-Holm procedure. Results The 23Na concentration increased successively from nawm to necrotic areas (mean ± sd: nawm = 37.84 ± 5.87 mM, edema = 54.69 ± 10.64 mM, gdce = 61.72 ± 12.95 mM, necrosis = 81.88 ± 17.53 mM) and the concentrations differed statistically significantly between all regarded areas (adjusted p-values for all pairwise comparisons

Introduction and importance There is no clear consensus on a specific treatment for esophageal perforation. The surgical approach is deemed necessary for local severe infection and pleural contamination requiring debridement. Presentations of case We have reported herein the case of a patient with esophageal perforation with severe mediastinal and thoracic abscess after endoscopic balloon dilation for stenosis due to endoscopic submucosal dissection and chemoradiotherapy. A surgical approach with primary closure was performed, but not found effective; while conservative treatment with mediastinal drainage via posterior neck and recovery of nutritional status was found to be effective. For the recovery of nutritional status, enteral nutrition was assessed using a polymeric formula through a percutaneous endoscopic gastrojejunostomy tube. Discussion Esophageal perforation is a life-threatening condition. Iatrogenic injuries are the frequent cause of esophageal perforation. For esophageal perforation, not only surgical interventions but also conservative treatments including various endoscopic approaches have been performed. If the inflammation is not localized, surgical intervention is often needed; however, if the patient's general condition is stable, conservative treatment with drainage, antibiotics, and nutritional management may be considered, even in cases of esophageal perforation. Conclusions Esophageal perforation with a large perforation site with widespread inflammation can be improved with proper thoracic and mediastinal drainage and adequate nutrition support if the patient's condition is mild., Highlights • Esophageal perforation is a life-threatening condition. • If the inflammation is not localized, a surgical approach is often needed. • When this occurs, drainage and nutritional management may still be effective. • If the patient responds to these treatments, surgical approach could be avoided.

Highlights • An esophagorespiratory fistula can cause severe pneumonia or a lung abscess. • Control of inflammation and initiation of chemoradiotherapy promptly. • Separation surgery provides good control of inflammation. • Separation surgery is less invasive and allows prompt initiation of chemoradiotherapy. • Drainage tube-less (DRESS) esophagostomy might improve patient’s quality of life., Introduction An esophagorespiratory fistula (ERF) can cause severe pneumonia or a lung abscess which progresses to life-threatening sepsis. A case of a patient with esophageal cancer and an esophagopulmonary fistula (EPF) who underwent separation surgery with drainage tube-less (DRESS) esophagostomy and was promptly started on definitive chemoradiotherapy (CRT) is reported. Presentation of case A 79-year-old man visited a clinic with a month-long history of dysphagia. Esophageal cancer at the middle thoracic esophagus was detected, and invasion of the left main bronchus and lower lobe of the right lung was seen on contrast-enhanced computed tomography (CT). Three weeks later, the patient was transferred to our hospital. CT showed a lung abscess in the lower lobe of the right lung that continued into the adjacent esophageal cancer. Due to the EPF, the patient underwent emergency surgery that consisted of esophageal separation surgery and double bilateral esophagostomy and enterostomy. Definitive CRT for the esophageal cancer was started from postoperative day 25. At six-month follow-up, the patient achieved relapse-free survival. Discussion Separation surgery with a DRESS esophagostomy provides good control of inflammation because of division of the respiratory tract from the alimentary tract, which allows prompt initiation of CRT. Alternatively, a DRESS esophagostomy allows patients to be free from any tube trouble. Conclusion Separation surgery with a DRESS esophagostomy for an ERF is a promising method to improve patient quality of life that is less invasive, controls inflammation, and facilitates subsequent definitive CRT.

Introduction: Anemia has long been associated with poor prognosis in patients with cervical cancer. Recently, additional hematologic parameters have emerged as potential indicators of worse outcome in this patient group. In a cohort of cervical cancer patients treated with chemoradiotherapy (CRT) and brachytherapy, we report on the prognostic significance of hematologic parameters including anemia, leukocytosis, neutrophil to lymphocyte ratio (NLR), and thrombocytosis, the effect of combining anemia with other hematologic parameters, and the effect of changes in hemoglobin levels during treatment. Materials and methods: Two-hundred fifty-seven cervical cancer patients were retrospectively identified from a single cancer institution’s database. Hematologic parameters were categorized as: anemia (hemoglobin ≤115 g/L), leukocytosis (white blood cell count >10 × 109/L), thrombocytosis (platelets >400 × 109/L), and NLR (ratio >5). The association between clinical factors and hematologic parameters on progression-free survival (PFS) and overall survival (OS) were assessed at 5 years. Results: At 5 years, both pre-treatment anemia (PFS: 60% vs 34%, p

Highlights • We report a case of esophageal cancer treated with PDT followed by esophagectomy. • We assessed the PDT effect on adjacent tissues based on surgery and pathology. • PDT can cause intense inflammation in tissues adjacent to the tumor. • The location should be considered when performing salvage esophagectomy after PDT., Introduction Photodynamic therapy (PDT) is performed as a salvage treatment for patients with residual or recurrent esophageal cancer after chemoradiotherapy (CRT). Although PDT is considered less invasive than salvage surgery, it is unclear how deep its effects are and whether it causes damage to adjacent tissues. Herein, we report a case of esophageal cancer treated with PDT followed by esophagectomy. In this case, we evaluated the effect of PDT on adjacent tissues based on surgical and pathological examination. Presentation of case A 58-year-old man with dysphagia was diagnosed with esophageal squamous cell carcinoma (SqCC; T1N0M0, Stage I) in the upper thoracic esophagus. He underwent definitive CRT with two courses of 5-fluorouracil and cisplatin every 4 weeks with 60 Gy of radiation. Twelve months after CRT, endoscopic examination revealed local recurrence, and PDT using talaporfin sodium was performed. The tumor recurred again 6 months after PDT, and robot-assisted thoracoscopic esophagectomy was performed as a definitive treatment. Tissues around the left side of the esophagus and thoracic duct were tightly adherent with severe fibrosis and were successfully removed by extended resection. Histopathological examinations showed that the esophageal wall and peri-esophageal tissue were replaced by fibrous tissue and this extended even beyond the tumor. Discussion The primary tumor was limited to the submucosal layer, and the target for irradiation had some longitudinal margins. Therefore, PDT can cause intense inflammation in tissues adjacent to the tumor. Conclusions It is necessary to consider the location when performing salvage esophagectomy after PDT.

Pretreatment nutritional and immunological status is useful for predicting survival outcomes for various types of malignant tumors. Our objective was to determine the impact of the pretreatment Onodera's prognostic nutritional index (OPNI) on outcomes of patients who underwent definitive chemoradiotherapy for advanced oral squamous cell carcinoma (OSCC). We reviewed 47 patients treated for OSCC with definitive chemoradiotherapy (CRT) at our institution between January 2004 and December 2011. We determined the OPNI according to the following formula: 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per μL). We determined the optimum OPNI cut-off through a receiver operating characteristic analysis. We analyzed the associations between OPNI status and various clinicopathological features and evaluated the effects of OPNI on the prognosis. We examined the relationships between OPNI and systemic inflammatory response parameters and analyzed intratumoral CD8+ T cells and their correlation with OPNI. The optimum OPNI cut-off was 42.7. A Kaplan–Meier curve analysis revealed that low OPNI was significantly associated with poor overall survival and cause-specific survival. The multivariate analysis revealed that low OPNI was independently correlated with poor 5 year overall survival and cause-specific survival. OPNI was significantly correlated with systemic inflammatory response parameters. Intratumoral CD8+ T cell counts in primary tumors were significantly lower for low OPNI than for high OPNI. The present data demonstrate that pretreatment OPNI is a valuable independent prognostic indicator of overall and cause-specific survival in advanced OSCC following definitive CRT. OPNI might reflect the tumor immune microenvironment characterization in OSCC., Highlights • The optimum Onodera's prognostic nutritional index (OPNI) cut-off was 42.7 in OSCC patients who underwent definitive chemoradiotherapy • Low OPNI was significantly associated with poor overall survival and cause-specific survival • OPNI was significantly correlated with systemic inflammatory response parameters • High-OPNI group showed significantly higher intratumoral CD8+ T cell counts in primary tumors

Highlights • The following case report describes the therapeutic course of a patient diagnosed with advanced thoracic esophageal squamous cell carcinoma invading the descending aorta. This is the first report of a salvage esophagectomy through a right thoracotomy followed by observation of the aortic invasion site through a left thoracotomy in a patient with T4b locally advanced esophageal squamous cell carcinoma., Introduction The surgical technique for esophagectomy to treat esophageal malignancies has been improved over the past several decades. Nevertheless, it remains extremely difficult to surgically treat patients with locally advanced T4b tumors invading the aorta or respiratory tract. Presentaion of case A 37-year-old Japanese man was diagnosed with T4b (descending aorta) N2M0, Stage IIIC middle thoracic esophageal squamous cell carcinoma. He was initially treated with definitive CRT followed by 3 courses of DCF. After the DCF, CT showed that the main tumor had shrunk and appeared to have separated from the descending aorta. Therefore we decided to perform a salvage esophagectomy. Because we needed the ability to closely observe the site of invasion to determine whether aortic invasion was still present, half the esophageal resection was performed under right thoracotomy, but the final resection at the invasion site was performed under left thoracotomy. Consequently, the thoracic esophagus was safely removed and aortic replacement was avoided. The patient has now survived more than 30 months after the salvage esophagectomy with no additional treatment for esophageal cancer and no evidence of recurrent disease. Discussion Because this and the previously reported procedures, each have particular advantages and disadvantages, one must contemplate and select an approach based on the situation for each individual patient. Conclusion Salvage esophagectomy through a right thoracotomy followed by careful observation of the invasion site for possible aortic replacement through a left thoracotomy is an optional procedure for these patients.

Preoperative chemoradiotherapy is widely used to improve local control of disease, sphincter preservation and to improve survival in patients with locally advanced rectal cancer. Patients enrolled in the present study underwent preoperative chemoradiotherapy, followed by surgical excision. Response to chemoradiotherapy was evaluated according to Mandard’s Tumor Regression Grade (TRG). TRG 3, 4 and 5 were considered as partial or no response while TRG 1 and 2 as complete response. From pretherapeutic biopsies of 84 locally advanced rectal carcinomas available for the analysis, only 42 of them showed 70% cancer cellularity at least. By determining gene expression profiles, responders and non-responders showed significantly different expression levels for 19 genes (P < 0.001). We fitted a logistic model selected with a stepwise procedure optimizing the Akaike Information Criterion (AIC) and then validated by means of leave one out cross validation (LOOCV, accuracy D 95%). Four genes were retained in the achieved model: ZNF160, XRCC3, HFM1 and ASXL2. Real time PCR confirmed that XRCC3 is overexpressed in responders group and HFM1 and ASXL2 showed a positive trend. In vitro test on colon cancer resistant/susceptible to chemoradioterapy cells, finally prove that XRCC3 deregulation is extensively involved in the chemoresistance mechanisms. Protein-protein interactions (PPI) analysis involving the predictive classifier revealed a network of 45 interacting nodes (proteins) with TRAF6 gene playing a keystone role in the network. The present study confirmed the possibility that gene expression profiling combined with integrative computational biology is useful to predict complete responses to preoperative chemoradiotherapy in patients with advanced rectal cancer.

Highlights • Our patient had hypopharyngeal perforation and pyogenic spondylitis post-CRT. • Our patient survived after receiving surgical and long-term antibiotic treatment. • No previous report has described a similar case., Introduction Chemoradiotherapy plays an important role in preserving function and morphology in head and neck cancer. However, in a few cases, chemoradiotherapy has been shown to result in late complications, such as hypopharyngeal perforation, which is very rare. Presentation of case A 65-year-old man, who had undergone chemoradiotherapy for hypopharyngeal cancer 30 months previously, presented with high fever and neck pain. He subsequently developed hypopharyngeal stenosis, hypopharyngeal perforation, and a retropharyngeal abscess followed by pyogenic spondylitis. He underwent surgical treatment (resection with reconstruction) and was administered an antibacterial agent and steroids for an extended period. This treatment regimen was successful, and the patient has survived disease-free without symptoms. Discussion Chemoradiotherapy-induced hypopharyngeal perforation is an extremely rare condition. In the present case, the perforation was large (2 cm), and the hypopharyngeal cavity was originally constricted. Pharyngeal reconstruction with a jejunal autograft was therefore necessary. Through the present case, we reconfirmed that although the primary purpose of chemoradiotherapy is organ preservation, it can also lead to organ destruction and fatal complications. It is important that physicians be aware of the possibility of hypopharyngeal perforation so as to avoid delayed diagnosis and treatment of similar rare cases. Conclusion Hypopharyngeal perforation can sometimes be fatal because it can lead to pyogenic spondylitis. Suitable surgical techniques and appropriate doses of antibacterial agents for long-term use were appropriate treatments for the patient in this case.