Advanced Rectal Carcinoma Research Articles

Pathological Complete Response Obtained with Chemotherapy in a Case of Locally Advanced Rectal Carcinoma

Pathological Complete Response Obtained with Chemotherapy in a Case of Locally Advanced Rectal Carcinoma

Success of teamwork: diagnosis and personalized treatment of advanced rectal carcinoma - case presentation

Abstract Background Finding the appropriate treatment for advanced rectal cancer patients represents a challenge for surgeons. Determining the right diagnosis and the proper treatment requires multidisciplinary collaboration. Our aim is to present a case with advanced stage rectum cancer, who received successful multidisciplinary treatment. Material and method A prospective multidisciplinary research is being conducted at our Department from 2018 within which patients with malignant rectal cancer are examined. Patients’ treatment is realized by the same multidisciplinary team. The patient’s preoperative investigations included MRI and a lymph node map designated by radiologists. Results In case of a 60-year-old patient the preoperative MRI showed a stenotic formation in the middle level of the rectum that penetrated the seminal vesicle. During surgery, we found a 10x10 cm stenotic, perforated rectal cancer, which penetrated the bladder, seminal vesicle, prostate and sacrum, respectively a metastatic lesion in the livers 8th segment. During surgery R2 recto-sigmoid resection was performed with colostomy. The patient was mobilized on the first postoperative day and bowel movements were regained on the second day. The patient left the hospital on the eighth postoperative day. Conclusions Adequate treatment of patients with advanced rectal cancer can be achieved only through multidisciplinary co-operation. Preoperative radiological examinations are mandatory. A map representing the positive colorectal lymph nodes, implemented by the radiologists, can significantly help the surgeons and pathologists.

Laparoscopic Posterior Pelvic Exenteration (Complete and Supralevator) for Locally Advanced Adenocarcinoma of the Rectum in Females: Surgical Technique and Short-Term Outcomes.

Background: Laparoscopic posterior exenteration (total and supralevator) is a complex and rarely done procedure. In this study we describe the surgical technique and short-term perioperative outcomes in 7 female patients of locally advanced carcinoma rectum operated with laparoscopic pelvic exenteration. Materials and Methods: We report 7 cases of carcinoma rectum involving either posterior wall of the uterus or vagina, which were operated with a laparoscopic procedure. All perioperative and intraoperative data were collected retrospectively from prospectively maintained electronic data. Results: Nine female patients with the diagnosis of nonmetastatic locally advanced lower rectal adenocarcinoma were selected. In MRI 4 patients had uterus-cervix involvement and 3 patients had a posterior vaginal wall and anal sphincter involvement. Four patients were operated with laparoscopic supralevator posterior exenteration and 3 patients were operated with laparoscopic complete posterior exenteration. Three patients underwent vaginal reconstruction, which was done with bilateral V-Y plasty. All 7 patients received neoadjuvant chemoradiotherapy (NACTRT), 3 patients also received additional chemotherapy (CAPOX regimen) due to poor response to NACTRT. Mean body mass index (BMI) was 23.85 (range 19-27.20). Mean duration for complete posterior exenteration was 9.63 hours (range 7-12 hours). Mean duration for supralevator posterior exenteration was 6.81 hours (range 6.25-7.5 hours). The mean postoperative stay was 10.71 days (range 7-16 days). Mean blood loss was 700 mL (range 200-1800 mL). On postoperative histopathology, all margins were free of tumor in all cases. Conclusion: Laparoscopic approach for locally advanced carcinoma rectum in female patients is feasible with less morbidity and safe short-term oncological outcomes. Careful selection of patients based on MRI is a must before undertaking the minimally invasive surgery approach. Long-term outcomes are still unknown and will require long-term follow-up.

Poorly differentiated neuroendocrine rectal carcinoma with uncommon immune-histochemical features and clinical presentation with a subcutaneous metastasis, treated with first line intensive triplet chemotherapy plus bevacizumab FIr-B/FOx regimen: an experience of multidisciplinary management in clinical practice

BackgroundNeuroendocrine tumors (NETs) are heterogeneous, widely distributed tumors arising from neuroendocrine cells. Gastrointestinal (GI)-NETs are the most common and NETs of the rectum represent 15, 2% of gastrointestinal malignancies. Poorly differentiated neuroendocrine carcinomas of the GI tract are uncommon. We report a rare case of poorly differentiated locally advanced rectal neuroendocrine carcinoma with nodal and a subcutaneous metastasis, with a cytoplasmic staining positive for Synaptophysin and Thyroid Transcription Factor-1.Case presentationA 72-year-old male presented to hospital, due to lumbar, abdominal, perineal pain, and severe constipation. A whole-body computed tomography scan showed a mass of the right lateral wall of the rectum, determining significant reduction of lumen caliber. It also showed a subcutaneous metastasis of the posterior abdominal wall. Patient underwent a multidisciplinary evaluation, diagnostic and therapeutic plan was shared and defined. The pathological examination of rectal biopsy and subcutaneous nodule revealed features consistent with small-cell poorly differentiated neuroendocrine carcinoma. First line medical treatment with triplet chemotherapy and bevacizumab, according to FIr-B/FOx intensive regimen, administered for the first time in this young elderly patient affected by metastatic rectal NEC was highly active and tolerable, as previously reported in metastatic colo-rectal carcinoma (MCRC). A consistent rapid improvement in clinical conditions were observed during treatment. After 6 cycles of treatment, CT scan and endoscopic evaluation showed clinical complete response of rectal mass and lymph nodes; patient underwent curative surgery confirming the pathologic complete response at PFS 9 months.Discussion and conclusionsThis case report of a locally advanced rectal NEC with an unusual subcutaneous metastasis deserves further investigation of triplet chemotherapy-based intensive regimens in metastatic GEP NEC.

Pathological Tumor Regression Grade Classifications in Gastrointestinal Cancers: Role on Patients' Prognosis.

Preoperative chemotherapy or combined radiotherapy and chemotherapy (CRT), followed by surgery, represents the standard approach for locally advanced esophageal, gastric, and rectal carcinomas. To adequately evaluate the effects of neoadjuvant CRT in the resection specimens, several histopathologic tumor regression grade (TRG) scoring systems have been introduced into clinical practice. The primary goal of these TRG systems relies on a correct prognostic stratification of patients in the attempt to help clinical decision-making and influence surgical strategies, postoperative adjuvant therapies, and surveillance intensity. However, most TRG systems suffer from poor reproducibility and low interobserver concordance rates. Many efforts have been made in the identification of alternative, robust, simple, and universally accepted TRG scoring systems, which would help in the comparison of different treatment strategies and in the standardization of multimodal therapies. The aim of this review is to analyze the most commonly used TRG systems in gastrointestinal cancers highlighting their pitfalls and usefulness, depending on the tumor type.

A prospective feasibility study evaluating the role of multimodality imaging and liquid biopsy for response assessment in locally advanced rectal carcinoma.

Colorectal cancer is a commonly encountered disease that poses several diagnostic and therapeutic challenges. The inherent heterogeneity of tumor biology and propensity to relapse despite "curative" resection pose significant challenges with regard to response assessment. Although MR imaging already plays a key role in primary staging of patients with rectal carcinoma, its reliability in restaging after neoadjuvant therapy is debatable (Van der broek et al. in Dis Colon Rectum 60(3):274-283, 2017). Therefore, there is significant interest in developing additional methods which may improve diagnostic accuracy. This study aims to evaluate the role of multimodality imaging and liquid biopsy in therapeutic response assessment. Seventeen patients were enrolled into the study over a span of 24months. All underwent hybrid PET-MRI and CT-perfusion (CT-P), prior to and following neoadjuvant therapy for locally advanced rectal carcinoma. Twelve of the 17 patients also underwent liquid biopsy, which consisted of blood sampling and analysis of circulating tumor cells (CTCs) and extracellular vesicles (EVs), includingcell fragments and microparticles (MPs), using the Cell Search System (Menarini Silicon Biosystems). SUV, DWI, and ADC were calculated during PET-MRI, and several parameters were evaluated during CT-perfusion, including average perfusion, blood flow (BF), blood volume (BV), mean transit time (MTT), permeability-surface area product (PS), contrast extraction efficiency (E), and K-trans (K). Changes observed pre- and post-neoadjuvant therapy in each modality were compared to tumor response at histopathology using a modified Ryan tumor regression grading system. Of the 17 patients included in the study, 14 were classified as non-responders, and 3 were classified as responders as determined by the modified Ryan Tumor Regression Grade (TRG) scoring system (Van der broek et al. in Dis Colon Rectum 60(3):274-283, 2017). When combined, blood markers and CT-P parameters (mean transit time (MTT), K-trans, and permeability-surfacearea product (PS)) produced the strongest models (p < 0.01). PET (SUV measurement) combined with CT-P-derived K-trans produced a marginally significant (p = 0.057) model for predicting response. MRI-derived ADC value did not provide a significant model for response prediction. A model of CT-P parameters plus liquid biopsy more accurately predicts tumor response than PET-MRI, CT-P alone, or liquid biopsy alone. These results suggest that in the evaluation of treatment response, liquid biopsy could provide additional information to functional imaging modalities such as CT-P and should therefore be explored further in a trial with larger sample size.

Intraoperative intraperitoneal chemotherapy increases the incidence of anastomotic leakage after anterior resection of rectal tumors.

BACKGROUNDIntraoperative intraperitoneal chemotherapy is an emerging treatment modality for locally advanced rectal neoplasms. However, its impacts on postoperative complications remain unknown. Anastomotic leakage (AL) is one of the most common and serious complications associated with the anterior resection of rectal tumors. Therefore, we designed this study to determine the effects of intraoperative intraperitoneal chemotherapy on AL.AIMTo investigate whether intraoperative intraperitoneal chemotherapy increases the incidence of AL after the anterior resection of rectal neoplasms.METHODSThis retrospective cohort study collected information from 477 consecutive patients who underwent an anterior resection of rectal carcinoma using the double stapling technique at our institution from September 2016 to September 2017. Based on the administration of intraoperative intraperitoneal chemotherapy or not, the patients were divided into a chemotherapy group (171 cases with intraperitoneal implantation of chemotherapy agents during the operation) or a control group (306 cases without intraoperative intraperitoneal chemotherapy). Clinicopathologic features, intraoperative treatment, and postoperative complications were recorded and analyzed to determine the effects of intraoperative intraperitoneal chemotherapy on the incidence of AL. The clinical outcomes of the two groups were also compared through survival analysis.RESULTSThe univariate analysis showed a significantly higher incidence of AL in the patients who received intraoperative intraperitoneal chemotherapy, with 13 (7.6%) cases in the chemotherapy group and 5 (1.6%) cases in the control group (P = 0.001). As for the severity of AL, the AL patients who underwent intraoperative intraperitoneal chemotherapy tended to be more severe cases, and 12 (92.3%) out of 13 AL patients in the chemotherapy group and 2 (40.0%) out of 5 AL patients in the control group required a secondary operation (P = 0.044). A multivariate analysis was subsequently performed to adjust for the confounding factors and also showed that intraoperative intraperitoneal chemotherapy increased the incidence of AL (odds ratio = 5.386; 95%CI: 1.808-16.042; P = 0.002). However, the survival analysis demonstrated that intraoperative intraperitoneal chemotherapy could also improve the disease-free survival rates for patients with locally advanced rectal cancer.CONCLUSIONIntraoperative intraperitoneal chemotherapy can improve the prognosis of patients with locally advanced rectal carcinoma, but it also increases the risk of AL following the anterior resection of rectal neoplasms.

Effect of neoadjuvant treatment on locally advanced rectal mucinous adenocarcinoma or signet-ring cell carcinoma: A post-hoc analysis from 3 prospective studies.

3608 Background: Mucinous adenocarcinoma and signet-ring cell carcinoma were uncommon in locally advanced rectal cancer. And it has been reported that both mucinous adenocarcinoma and signet-ring cell carcinoma showed poor response to standard neoadjuvant chemoradiotherapy. Here, we tried to compare the efficacy of different neoadjuvant treatment regimen on locally advanced rectal mucinous adenocarcinoma or signet-ring cell carcinoma (M/S). Methods: We enrolled patients with locally advanced rectal cancer from 3 prospective clinical trials (NCT01211210, NCT02217020 and NCT02887313), including FOWARC study (N = 309), mFOLFOXIRI neoadjuvant chemotherapy trial (N = 103) and the total neoadjuvant treatment with FOLFOX and radiotherapy (N = 129). Among the 541 patients, 41 (7.6%) patients were M/S and 500 were non-M/S. Totally, 7 M/S patients and 84 non-M/S patients received 5FU concurrent with radiotherapy (Group A), 20 M/S patients and 208 non-M/S underwent FOLFOX concurrent with radiation or total neoadjuvant treatment (Group B), 11 M/S patients and 92 non-M/S patients underwent mFOLFOXIRI neoadjuvant chemotherapy alone (Group C). Other 3 M/S patients and 116 non-M/S patients received FOLFOX neoadjuvant chemotherapy alone (Group D). Results: Among M/S patients, only 4 (9.7%) achieved pathologic complete response (pCR), and 6 (14.6%) patients had tumor downstaging to ypstage 0-I. In group A, the pCR rate was 14.3% and 11.9% (p = 0.85), and the tumor downstaging rate was 14.3% and 36.9% (p = 0.22) in M/S and non-M/S patients, respectively. In group B, the pCR rate was 15.0% and 34.6% (p = 0.07), and the tumor downstaging rate was 25.0% and 60.1% (p = 0.002) in M/S and non-M/S patients, respectively. However, in group C and group D with chemotherapy alone as neoadjuvant treatment, no M/S patients showed pCR or tumor downstaging; while in non-M/S patients higher tumor downstaging rate was observed. Conclusions: M/S showed resistance to neoadjuvant chemotherapy along regimens. Even with chemoradiotherapy, M/S patients showed poorer response than that of non/M/S patients. Further study was warranted to explore the new regimen for M/S patients. [Table: see text]

Prognostic factors for severe diarrhea in patients with locally advanced rectal carcinoma treated with neoadjuvant chemoradiation with capecitabine: A single-center cohort study.

e15176 Background: Chemoradiation with concomitant capecitabine (CRT) followed by total mesorectal excision is the standard of care for locally advanced rectal carcinoma (LARC). Grade ≥ 3 diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiotherapy. The aim of this study is to describe the risk factors of grade ≥ 3 diarrhea in patients with LARC during CRT. Methods: A single centre retrospective cohort study was conducted in our tertiary center. All patients with LARC treated with CRT from 2009 to 2015 were included. Patients with local recurrence who received CRT for the first time were also included. Univariate logistic regression analyses were used, followed by a multivariate analysis of the significant factors with backward selection at p &lt; 0.05. Results: A total of 738 patients were included: 67% male, median age 64 years (range 17-88), 95% primary presentation. DPYD-testing was not performed upfront. In this cohort 69 patients (9%) developed ≥3 grade diarrhea. In the univariate analysis, factors significantly associated with ≥3 grade diarrhea were; female gender, age ≥65 years, body weight and decreased renal function (defined as MDRD GFR &lt; 60 ml/min/1,73 m2). The following factors remained significantly associated with ≥3 grade diarrhea in the multivariate analysis; female gender (odds ratio (OR) 2.77, 95% confidence interval (CI) 1.54-4.99, p 0.001), age ≥65 years (OR 2.85, 95% CI 1.63-4.98, p &lt; 0.001) and a lower bodyweight (OR 0.98, 95% CI 0.96-1.00, p 0.015). Conclusions: Female gender and age ≥65 years significantly increase the risk of grade ≥ 3 diarrhea caused by neoadjuvant CRT for LARC. So, older female patient must be closely watched during this treatment to intervene on time. The difference in toxicity between females and males might be explained by the pelvic anatomical differences between men and women. The found prognostic factors will be validated in a second cohort of patients with LARC treated with CRT. Besides, sarcopenia will be tested as a prognostic factor as well.

Evaluation of Dworak grading system as a prognostic indicator after neoadjuvant chemoradiotherapy in rectal cancer patients.

e15053 Background: The objective of this study was to assess the prognostic role of Tumor Regression Grading (TRG) according to the Dworak system on progression free survival (PFS) after chemoradiotherapy (CRT) in locally advanced rectal cancer. Methods: In total, 159 patients with locally advanced rectal cancer who underwent neoadjuvant CRT from January 2007 and December 2016 were enrolled. PFS (any relapse after surgery) was tested against TRG (Dworak grade 1+2 versus Dworak grade 3+4) and other potential risk factors (age, gender, pre- and postoperative T-stage, pre- and postoperative N-stage, grading, lymph invasion, vessel invasion, chemotherapy regime, resection margin, treatment delay). Risk factors with a highly significant influence (p &lt; 0.01) in the univariate Kaplan-Meier (KM) estimation were tested for independence using the multivariate cox regression model. Results: With a mean follow-up of 42.5 months, 5 years and 10 years estimated PFS for all patients was 60.1% and 49.1% respectively. Estimation of 5 years and 10 years PFS was 49.7% and 45.5% for TRG Dworak grade 1+2 (n = 109) and 83.8% and 67% respectively for TRG Dworak grade 3+4 (n = 50). This difference was highly significant (p &lt; 0.001). Other highly significant risk factors were postoperative N-stage (negative versus positive), lymph invasion (L0 versus L1), and resection margin (R0 versus R1/2). In the multivariate analysis, only TRG and post-op N-stage were identified as independent risk factors for PFS. Conclusions: In this analysis, Dworak Tumor Regression Grading appears to be a prognostic marker for oncologic outcomes in locally advanced rectal carcinoma patients treated with neoadjuvant CRT.

Increased Levels of Genomic Instability and Mutations in Homologous Recombination Genes in Locally Advanced Rectal Carcinomas.

Pre-operative 5-fluoracil-based chemoradiotherapy (nCRT) is the standard treatment for patients with locally advanced rectal cancer (LARC). Patients with pathological complete response (pCR–0% of tumor cells in the surgical specimen after nCRT) have better overall survival and lower risk of recurrence in comparison with incomplete responders (pIR). Predictive biomarkers to be used for new therapeutic strategies and capable of stratifying patients to avoid overtreatment are needed. We evaluated the genomic profiles of 33 pre-treatment LARC biopsies using SNP array and targeted-next generation sequencing (tNGS). Based on the large number of identified genomic alterations, we calculated the genomic instability index (GII) and three homologous recombination deficiency (HRD) scores, which have been reported as impaired DNA repair markers. We observed high GII in our LARC cases, which was confirmed in 165 rectal cancer cases from TCGA. Patients with pCR presented higher GII compared with pIR. Moreover, a negative correlation between GII and the fraction of tumor cells remaining after surgery was observed (ρ = –0.382, P = 0.02). High HRD scores were detected in 61% of LARC, of which 70% were incomplete responders. Using tNGS (105 cancer-related genes, 13 involved in HR and 5 in mismatch repair pathways), we identified 23% of cases with mutations in HR genes, mostly in pIR cases (86% of mutated cases). In agreement, the analysis of the TCGA dataset (N = 145) revealed 21% of tumors with mutations in HR genes. The HRD scores were shown to be predictive of better response to PARP-inhibitors and platinum-based chemotherapy in breast and ovarian cancer. Our results suggest that the same strategy could be applied in a set of LARC patients with HRD. In conclusion, we identified high genomic instability in LARC, which was related to alterations in the HR pathway, especially in pIR. These findings suggest that patients with impaired HRD would clinically benefit from PARP-inhibitors and platinum-based therapy.

Computerized Tomography Criteria as a Tool for Simplifying the Assessment of Locally Advanced Rectal Cancer

Rectal cancer represents a leading cause of mortality worldwide. Staging defines the local and distant extent of the disease, guides management, and predicts prognosis. Different modalities are available for staging including TRUS (transrectal ultrasound), CT (computed tomography), and MRI (magnetic resonance imaging). The objective of this study was to screen and isolate CT imaging parameters suggestive of advanced rectal cancer and its utility as a tool in simplifying the staging protocol making further imaging studies unnecessary. Retrospective, single center study. Seventy-five patients with rectal carcinoma were included and were divided into two groups according to their T score and nodal involvement status, as diagnosed by TRUS. Group 1 (n = 15) "local disease" (T1/T2 N0) and group 2 (n = 60) "locally advanced disease" are both eligible for neoadjuvant treatment (N/any T or T3/any N). For each patient, three CT imaging parameters that represent locally advanced disease, i.e., perirectal fat infiltration, local lymphadenopathy, and rectal wall thickening, were evaluated and compared between the two groups. The capability of CT imaging to accurately predict locally advanced rectal carcinoma. Rectal wall thickening on CT was found to have 92% PPV and perirectal lymphadenopathy 96% PPV for predicting a locally advanced stage. A combination of those two parameters results in a predictive PPV of 98%. This was a single center retrospective study, with a relatively small cohort. CT is a valuable tool in the assessment and management of rectal carcinoma as it can identify locally advanced rectal cancer. This enables treatment without any further unnecessary evaluation.

Long-term results of a multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (JACCRO CC-04: SHOGUN Trial)

PurposeThe study was designed to evaluate the safety and efficacy of adding oxaliplatin to py (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). We report here the final results of the study. Patients and methodsPatients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. They received oral S-1 (80 mg/m2/day on days 1–5, 8–12, 22–26, and 29–33) and infusional oxaliplatin (60 mg/m2/day on days 1, 8, 22, 29) plus radiotherapy (1.8 Gy/day, total dose of 50.4 Gy in 28 fractions), with a chemotherapy gap in the third week of radiotherapy. Primary endpoint of the study was pathological complete response (pCR) rate. Secondary endpoints were rates of R0 resection, down-staging, cumulative 3-year local recurrence, 3-year disease-free survival (DFS), and toxicity. ResultsForty-five patients were enrolled at six centers in Japan. All patients received CRT, and 44 underwent operation. The pCR rate was 27.3% (12/44). The R0 resection rate was 95.5% (42/44). T-down-staging rate was 59.1% (26/44), and N-down staging rate was 65.9% (29/44); the combined pathological down-staging rate was 79.5% (35/44). There were no grade 4 adverse events, but 11.1% of the patients had grade 3 adverse events. Cumulative 3-year local recurrence rate was 0%. However, 13 (30.0%) patients suffered from distant metastasis, and one patient suffered from secondary esophageal cancer that was unrelated to rectal cancer. Eight patients had lung metastasis, 4 had liver metastasis, and 3 patients died of the metastatic disease. The 3-year DFS rate of the 44 patients was 67.5% (median follow-up 36.3 months), and the 3-year overall survival (OS) rate was 93.0% (median follow-up 39.6 months). The patients were then divided into the pCR (12 patients) group and non pCR (32 patients) group. The 3-year rate of DFS for each group was 91.7% and 58.1% and that of OS was 100% and 90.3%, respectively. ConclusionsThe study showed a high pCR rate with no severe toxicity, good follow-up results, and good loco-regional control. Therefore, addition of oxaliplatin to preoperative CRT with S-1 in patients with LARC might be feasible and lead to better local control than standard treatment.

Prognostic value of tumour-infiltrating CD8+ lymphocytes in rectal cancer after neoadjuvant chemoradiation: is indoleamine-2,3-dioxygenase (IDO1) a friend or foe?

The prognostic value of the local immune phenotype in patients with colorectal cancer has been extensively studied. Neoadjuvant radiotherapy and/or chemotherapy may potentially influence these immune responses. In this study, we examined the prognostic role of indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) in locally advanced rectal carcinomas after neoadjuvant treatment. Expression of IDO1 and CD8 was evaluated by immunohistochemistry in 106 archival tumour tissue samples from patients following neoadjuvant chemoradiation and radical resection. The average infiltration of IDO1+ and CD8+ cells was calculated along the tumour invasive front, in the tumour centre and within the neoplastic cells and expressed as total scores. Of the tumour specimens evaluable for immunohistochemistry, 100% showed CD8+ lymphocyte infiltration and 93.4% stained positive for IDO1. Total IDO1 score positively correlated with total CD8 score for all three subsites (p = 0.002, Kendall-tau-b 0.357). A high total CD8 score was positively correlated with lower ypUICC-stages (p = 0.047) and lower ypT-categories (p = 0.032). Total IDO1 expression showed a clear trend towards a lower risk of recurrence (p = 0.078). A high total IDO1 score was an independent prognostic marker for prolonged disease-free survival (HR 0.38, p = 0.046) and a high total CD8 score for favourable overall survival (HR 0.16, p = 0.029). Analysis of the local CD8 and IDO1 expression profile may be a helpful tool in predicting prognosis for patients with locally advanced rectal cancer following neoadjuvant chemoradiation.

Concomitent Chemotherapy and radiotherapy in patients with Locally Advanced Rectal Carcinoma

Introduction:In recent years, the approach to adjuvant therapy for rectal cancer in the United States and Europe has been shifting toward preoperative therapy to promote sphincter-preserving surgery and decrease acute and late bowel toxicity. Patients&Methods:This study will be a phase II trial to study the effectiveness of combining chemotherapy (Gemcitabine) and external – beam radiotherapy followed by surgery in treating patients who have locally advanced rectal cancer , It is carried on Sohag University Hospital & Sohag NCI since( October 2014- December2017),the dose of radiotherapy 5040 cGy /28ttt,and chemotherapy dose is 45mg/m2 given twice weekly during radiotherapy sessions only, the study included 30 patients (age 18 and over), having rectal cancer with the following eligibility criteria:histologically proven ,previously untreated rectal carcinoma , every patient in the study was subjected to the following:history & physical examination,laboratory investigations, radiological studies. Results:Thirty patients were included in the study,13 females (43.3%) and 17 male( 56.6%) mean of the age was 49 years. (range24-65year), most of them had adenocarcinoma of the rectum, the main presenting symptom was bleeding per rectum(56.7%), as regard to the response to the neoadjuvant treatmen 12/30 patients (40%) achieved Partial response, 8/30patients(27.6%) achieved complete response and 10/30 patients (33%) had no response, abdomino - perineal resection was performed in 19 patients(63.3%) and 11 patients (36.7%) underwent sphincter preservation operation, about the toxicity in this study,for chemotherapy diarrhea was the most common manifestation which seen in 25 patients(83%),followed by loss of appetite seen in 9 patients(63.3%), for radiotherapy 19 patients (63%) developed wet desquamation. the rate of Overall Survival of the 2-years study is (80%),the Disease free survival is (63%)while the progression free survival is (72%),N stage was the only significant factor affecting the disease free survival and overall survival. Conclusion: Pre-operative chemo-radiotherapy in dose and fractionation schedule used is safe, effective and well tolerated, allowed sphincter preservation which performed in (36.7%) of patients

Neoadjuvant Chemotherapy and Radiotherapy in Locally Advanced Rectal Carcinoma

Background: Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor size and recurrence, but also increase the tumor resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy alone, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage. Middle and low rectal cancers can benefit more from neoadjuvant chemradiotherapy than high rectal cancer. Aim of the work: 1- Selection of suitable neoadjuvant chemoradiotherapy method with less acute and late toxicity effect. 2- Discover which drug or combination of drugs have better results in terms of local recurrence and survival . 3- Selection of appropriate patients and irradiation modes for neoadjuvant chemoradiotherapy. Methods: Three major databases(PubMed,MEDLINE and Cochrane library). The review included articles published in English in NCCN Journal and ASCO Journal from January 2012 t0 march 2018. Conclusion: Preoperative chemoradiotherapy has been recommended as the standard treatment for locally advanced middle and low rectal cancer.

A Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Squamous Cell Carcinoma: Two Case Reports

A Complete Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Squamous Cell Carcinoma: Two Case Reports

16. Predicting neoadjuvant therapy response in locally advanced rectal cancer using texture features

Purpose To predict pathological response to neoadjuvant chemo-radiotherapy (CRT) in locally advanced rectal carcinoma (LARC), using a classifier based on texture features derived from MRI and PET acquisitions. Methods 47 patients with: (a) histologically diagnosis of LARC, (b) pre-treatment MRI and PET/CT, (c) neoadjuvant treatment consisting of 46–55 Gy in 23–30 RT fractions alone or in association with either infusional 5-FU or oral Capecitabine, and (d) total mesorectal excision were included in this study. Patients with complete (tumour regression grade, TRG = 1) or near complete (TRG = 2) regression were defined as responders (pR+), while patients with moderate (TRG = 3) to no regression (TRG = 5) were considered as non-responders (pR−) [1] , [2] . Before implementing texture analysis, tumours were semi-automatically segmented on T2-w MRI, ADC maps and PET/CT acquisitions. From the segmented tumours, the following quantitative features were extracted from T2-w, ADC and PET images: (a) first-order parameters: median, mean, percentiles (10th, 25th, and 75th), (b) SUV, metabolic volume and glycolytic volume only for PET images, and (c) 22 s-order texture parameters, derived from Haralick analysis [3] . Multivariate logistic regression was performed to identify features most correlated with TRG. Results Overall, 26 patients were classified as pR−, and 21 as pR+ after total mesorectal excision. Parameters included in the multivariate regression were “10th percentile PET”, “10th percentile T2-w”, “Homogeneity ADC”, “Homogeneity PET”, “Information measure of correlation T2-w” (p = 0.002). The area under the ROC curve was 0.83 (95% confidence interval = 0.69–0.93), sensitivity and specificity were 75% and 76%, respectively, in detecting responders. Conclusions Texture analysis could provide useful information in assessing response to neoadjuvant treatment in LARC patients. These preliminary results, if confirmed on larger dataset, could be useful to personalize the oncological pathway for patients, delaying or advancing surgery, according to the prediction of treatment response.

Cyclin-dependent kinase 1 targeting improves sensitivity to radiation in BRAF V600E colorectal carcinoma cells.

Preoperative chemoradiation is currently the standard of care in locally advanced rectal carcinoma, even though a subset of rectal tumors does not achieve major clinically meaningful responses upon neoadjuvant chemoradiation. At present, no molecular biomarkers are available to predict response to neoadjuvant chemoradiation and select resistant tumors willing more intense therapeutic strategies. Thus, BRAF mutational status was investigated for its role in favoring resistance to radiation in colorectal carcinoma cell lines and cyclin-dependent kinase 1 as a target to improve radiosensitivity in BRAF V600E colorectal tumor cells. Colony-forming assay and apoptotic rates were evaluated to compare the sensitivity of different colon carcinoma cell lines to ionizing radiation and their radiosensitivity upon exposure to BRAF and/or cyclin-dependent kinase 1 inhibitory/silencing strategies. Cyclin-dependent kinase 1 expression/subcellular distribution was studied by immunoblot analysis. Colon carcinoma BRAF V600E HT29 cells exhibited poor response to radiation compared to BRAF wild-type COLO320 and HCT116 cells. Interestingly, neither radiosensitizing doses of 5-fluoruracil nor BRAF inhibition/silencing significantly improved radiosensitivity in HT29 cells. Of note, poor response to radiation correlated with upregulation/relocation of cyclin-dependent kinase 1 in mitochondria. Consistently, cyclin-dependent kinase 1 inhibition/silencing as well as its targeting, through inhibition of HSP90 quality control pathway, significantly inhibited the clonogenic ability and increased apoptotic rates in HT29 cells upon exposure to radiation. These data suggest that BRAF V600E colorectal carcinoma cells are poorly responsive to radiation, and cyclin-dependent kinase 1 represents a target to improve radiosensitivity in BRAF V600E colorectal tumor cells.

Early recurrence and progression of a rare rectal squamous cell carcinoma after initial response to primary chemoradiotherapy.

Rectal squamous cell carcinomas represent an extremely rare malignancy which carries a significant morbidity and mortality. Diagnosis requires distinction from squamous cell carcinoma of the anus and colonic adenocarcinoma by endoscopy and histopathological examination of a biopsy. Due to the rarity of the pathology, available evidence is limited and optimum management has yet to be elucidated. Older reports favored radical surgical management, but recent reports in the literature recommend judicious use of primary chemoradiotherapy. We herein report the diagnosis and management of a male patient with an aggressive, locally advanced rectal squamous cell carcinoma treated with good results with primary chemoradiotherapy. Six months after completion of therapy, however, extensive recurrence and metastases were diagnosed. This case highlights the need for stringent clinical and radiological follow-up.