Advanced Rectal Carcinoma Research Articles

186P Neoadjuvant radiotherapy of locally advanced rectal cancer: short-course radiation VS long-course chemo radiation

Aim/Background: To compare toxicity profile, patient compliance, surgical resectability & pathological response in short course radiation vs long course chemoradiation in locally advanced rectal cancer. Methods: All patients underwent staging workup as per NCCN guidelines. 87 patients with stage II to III rectal cancer were treated with short course(SC) radiation(RT) (25Gy/5Fr followed by surgery within 10 days, n= 36) or long course(LC) chemoRT (50.4Gy/28Fr with chemotherapy with 5FU 375mg/m2 and calcium leucoverin 20mg/m2 in 1st & last week of RT followed by surgery after 6–8 weeks, n = 51). Acute toxicities were assessed using revised RTOG criteria. The resectability potential were accessed by R0, R1 and R2 resections. Histopathological reporting was done by a single pathologist. The patients were characterised into three–(1) complete pathological response (2) down staging response (3) stable or progressive disease (both 1 & 2 are considered as down staging ‘ + ’ and 3 as down staging ‘-’). Patient compliance assessed based on the extend of completion of planned treatment. Results: 80 out of the 87recruited patients received neoadjuvant treatment & 59 completed the planned treatment. About half of the patients in LC CRT arm developed skin & GI toxicities (p <.001). 2 patients developed haematological toxicities.In the SCRT arm none developed skin, GI or haematological toxicities. R0 resection was 100% & 78.3% in LC CRT & SCRT arms respectively (p = 0.007). The pathological response for T(p = 0.004) & N(p = 0.026) status were 83.3% & 94.4% and 47.8% & 69.6% for LC CRT & SCRT arms respectively. Regarding the treatment compliance 70.6% in the LC CRT arm & 63.9% in the SCRT arm completed the planned treatment (p = 0.510). Conclusions: The incidence of GI and skin toxicities were significantly high in LC CRT arm but they were managable with no treatment related deaths. With regard to downstaging & pathological complete response LC CRT is significantly better than SCRT. Our results are similar to various other international trials. To conclude, the results are favouring long course chemo radiotherapy ahead of short course radiotherapy in managing locally advanced carcinoma rectum with acceptable treatment related toxicities. Clinical trial identification: CTRI/2013/09/004035 Disclosure: All authors have declared no conflicts of interest.

Is it safe to omit neoadjuvant chemo-radiation in mucinous rectal carcinoma?

BackgroundPurpose was to compare the oncologic outcome of neoadjuvant chemoradiotherapy (nCXRT) versus postoperative chemoradiotherapy (pCXRT) for locally advanced mucinous rectal carcinoma (MRC) having curative total mesorectal excision (TME). MethodsOne hundred and two patients with MRC (T3-4 and/or N1-2) of middle and lower third rectum were included. Patients were non-randomly divided into 2 groups: Group A (N = 61) had nCXRT followed by total mesorectal excision (TME) after 8–11 weeks and Group B (N = 41) had TME followed by pCXRT. Primary end points were disease free survival (DFS) and overall survival (OS). Secondary endpoints were tumor regression grade (TRG) and morbidity. ResultsIn group A, 29 patients had partial response after nCXRT, 26 patients showed no change and 6 patients had progression. TME was done in 55 patients in group A and 41 patients in group B. Six patients in group A turned to be unresectable after nCXRT due to progressive disease. Mean follow-up was 53 months. In patients received TME, Four-year DFS was higher in group A compared to group B yet not statistically significant (DFS 0.69 [95% CI 0.54–0.85] vs. 0.67 [95% CI 0.47–0.87]; P = 0.39). However, actuarial 4 years OS was comparable in both groups (0.72 [95% CI 0.59–0.91] vs. 0.70 [95% CI 0.55–0.88]; P = 0.46 in groups A and B respectively). Multivariate analysis revealed that age <40, and N2 were risk factors of recurrence. ConclusionWhilst accepting that the numbers are small, there was no statistical difference in outcome (DFS and OS) between patients receiving pre- or post-operative chemo-radiotherapy. In most MRC patients, tumor regression is not significant after nCXRT and there is considerable possibility of tumor progression during nCXRT treatment. So, nCXRT should be used with close follow-up in MRC for early detection of possible tumor progression. If the patient cannot tolerate nCXRT, it is possibly safe to do surgery followed by pCXRT. Prospective study is needed to study the value of nCXRT in MRC.

Osteopontin level correlates negatively with tumor shrinkage in neoadjuvant chemoradiation of locally advanced rectal cancer

&lt;strong&gt;Background and Purpose&lt;/strong&gt;: Neoadjuvant chemoradiation (CRT) is the mainstay treatment for locally advanced rectal carcinoma. However, the response is varied due to many factors, including tissue hypoxia. Osteopontin (OPN) is an emerging endogen hypoxic marker with significant correlation towards tumor pO2, also a more accurate chronic hypoxic marker compared to carbonic anhydrase IX (CAIX), glucose transporter 1 (GLUT1), and lactate dehydrogenase A (LDHA); but as far as we know there is no research that measured OPN quantity in rectal cancer tissue and correlated it with tumor shrinkage response in neoadjuvant CRT. &lt;strong&gt;Materials and Method&lt;/strong&gt;: Fourteen patients that met the inclusion and exclusion criteria were analyzed retrospectively. Imaging was evaluated for tumor shrinkage percentage and categorized based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. OPN level quantitative results from rectal cancer tissue were obtained using ELISA method. &lt;strong&gt;Results&lt;/strong&gt;: The mean OPN concentration was 0.568 ± 0.26 ng/mL. There was a significant strong negative correlation (&lt;em&gt;r &lt;/em&gt;= −0.630, &lt;em&gt;p &lt;/em&gt;= 0.016) between the OPN level and tumor shrinkage. OPN cut off value of ≥0.538 ng/mL predicted non-responsiveness of tumor shrinkage in neoadjuvant CRT with 100% sensitivity and 81.8% specificity. &lt;strong&gt;Conclusion&lt;/strong&gt;: Hypoxia occurred in locally advanced rectal carcinoma patients. Higher level of OPN correlates negatively with tumor shrinkage, proved worse response of CRT given.&lt;p&gt; &lt;/p&gt;

A multicenter phase II study of preoperative chemoradiotherapy with S-1 plus oxaliplatin for locally advanced rectal cancer (SHOGUN trial)

PurposeThis study was designed to evaluate the safety and efficacy of adding oxaliplatin to preoperative chemoradiotherapy (CRT) with S-1 in patients with locally advanced rectal carcinoma (LARC). Patients and methodsThis was a multicenter phase II study in patients with histologically proven clinical stage T3 or T4 (any N, M0) LARC. Patients preoperatively received oral S-1 (80mg/m2/day on days 1–5, 8–12, 22–27, and 29–33) and infusional oxaliplatin (60mg/m2 days on 1, 8, 22, and 29) plus radiotherapy (50.4Gy), with a chemotherapy gap in the third week of radiotherapy. Pathological complete response (pCR) was the primary endpoint. Secondary endpoints included toxicity, compliance, R0 resection rate, and downstaging rate. ResultsA total of 45 patients were enrolled at six centers in Japan. All 45 patients received CRT, and 44 underwent operation. A pCR was achieved in 12 (27.3%) of the 44 patients who underwent surgery. Near-total tumor regression was confirmed in 47.7%. There were no grade 4 adverse events, and 11.1% of the patients had grade 3 adverse events. R0 resection was achieved in 95.5% of the patients. ConclusionPreoperative CRT with S-1 plus oxaliplatin had a high pCR rate and a favorable toxicity profile.

PTU-206 Downstaging by further chemotherapy for poor responders to chemoradiotherapy in inoperable rectal cancers – prospective study

<h3>Introduction</h3> The patients with locally advanced unresectable rectal cancers who were still inoperable on MRI imaging were further treated with 4 to 6 cycles of chemotherapy and reassessed for resectability. <h3>Method</h3> Patients with locally advanced carcinoma rectum assessed to have unresectable disease on MRI at presentation received neoadjuvant radiation to a dose of 50 Gy in 1.8 to 2 Gy daily fractions with concurrent capecitabine chemotherapy 825 mg/m²daily. A follow up MRI was done 6 weeks after completion of NACRT and assessed in a joint multidisciplinary meeting. Those with persisting unresectable local disease on MRI were planned for 4 cycles of chemotherapy followed by reassessment imaging for resectability. We present the results of the patients with poor response to NACTRT having further treated by the chemotherapy. <h3>Results</h3> From Jan 2013 till December 2014, 50 patients with unresectable rectal cancer recieving NACRT were still found to have unresectable disease on MRI. They were planned for further chemotherapy with FOLFIRINOX or FOLFOX based regimens. Thirty three (67%) patients had radiological evidence of partial regression and one patient died of neutropenic sepsis. Of these 22 (37%) patients underwent R0 resection and another 10 are scheduled for surgery. Eight patients were still inoperable and 5 were detected to have peritoneal metastasis during surgery were given further palliative chemotherapy. One patient was lost to follow-up and 1 died due to sepsis. Four patients had complete pathological response. <h3>Conclusion</h3> Achieving margin negative resection in these patients is an encouraging starting point for further research in this subset. Whether this continued decrease in primary tumour volume can be attributed to delayed response to radiotherapy or addition of further chemotherapy, or both, is yet to be ascertained. Hence for patients with advanced local disease not yet in palliative stage, further intensive chemotherapy with clinicoradiological follow-up should be done to facilitate successful surgical resection. <h3>Disclosure of interest</h3> None Declared.

A functional biological network centered on XRCC3: a new possible marker of chemoradiotherapy resistance in rectal cancer 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 = 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.

EP-1643: A dosimetric comparison of 3D-CRT, IMRT and VMAT techniques for locally advanced rectal carcinoma

EP-1643: A dosimetric comparison of 3D-CRT, IMRT and VMAT techniques for locally advanced rectal carcinoma

Detection of morphologic alterations in rectal carcinoma following preoperative radiochemotherapy based on multiphoton microscopy imaging

BackgroundPreoperative radiochemotherapy improves outcomes in patients with locally advanced rectal carcinoma, and has been used increasingly in patient management. However, there is a strong clinical need to assess tumor response to neoadjuvant treatment, and a non-invasive technique that allows the precise identification of morphologic changes in tumors would be of considerable clinical interest.MethodsIn this study, we used multiphoton microscopy (MPM) to detect morphologic alterations in rectal adenocarcinomas in patients treated with preoperative radiochemotherapy.ResultsMPM was able to identify histopathologic alterations in rectal cancer following preoperative radiochemotherapy, and allowed the qualitative assessment of treatment efficacy and feasibility in relation to dose or strategy.ConclusionThese findings may provide the groundwork for evaluating tumor response to neoadjuvant treatment, thus allowing the tailoring of effective treatment doses and strategies.

Association of beclin 1 expression with response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinoma.

Beclin 1 is an essential regulator of autophagy that is induced in response to cellular stress and serves to maintain cell survival in established tumors. We recently demonstrated that Beclin 1 suppression can sensitize colorectal cancer cells to radiation-induced DNA damage and apoptosis. Therefore, we hypothesized that the level of Beclin 1 expression may be associated with radiation sensitivity in vivo. We determined the association of Beclin 1 expression in pretreatment rectal cancer tissues with response to neoadjuvant chemoradiation in surgical resection specimens. Stages II and III (n = 96) rectal adenocarcinoma patients were treated with neoadjuvant chemoradiation followed by surgical resection with curative intent. Beclin 1 was analyzed by immunohistochemistry and the expression level was dichotomized at the median value with categorization into low and high groups. We identified 56 (58.3%) and 40 (41.7%) patients whose tumors had high- versus low-level Beclin 1 expression, respectively. Rectal cancers with high versus low Beclin 1 expression were significantly less likely to be downstaged after chemoradiation treatment (45% [25/55] vs. 58% [22/38]; p = 0.02). In a multivariable analysis adjusted for age, sex, histological grade and baseline tumor node metastasis (TNM) stage, the impact of Beclin 1 expression on tumor downstaging remained statistically significant (p = 0.03). The association of the level of Beclin 1 expression with the rate of tumor downstaging after chemoradiation is consistent with in vitro data, and suggests that Beclin 1 may be a predictive biomarker for the efficacy of chemoradiation in patients with rectal cancer.

Induction FOLFOX followed by preoperative hyperfractionated radiotherapy plus bolus 5-fluorouracil in locally advanced rectal carcinoma: single arm phase I–II study

Induction chemotherapy has many benefits of in locally advanced rectal cancer (LARC); one of these is the better control of distant failure. Hyperfractionated radiotherapy (HFRT) is new approach still on evaluation in preoperative setting of rectal cancer. We aimed to evaluate the efficacy of induction FOLFOX followed by HFRT in LARC. From September 2011 to December 2013, 27 patients with LARC were enrolled in this prospective, phase I-II study. Induction FOLFOX bolus was given for two cycles followed by HFRT (1.5 Gy twice day for 30 fractions over 3 weeks for a total of 45 Gy). 5-fluorouracil (5-FU) bolus was administrated during first and last 3 days of radiotherapy. Surgical resection was performed in 4-5 weeks further and followed by adjuvant FOLFOX bolus regimen. Twenty-one (77.8 %) patients were males and 22. 2 % of patients were females, and the median age at diagnosis was 46 years. Low sited tumor was the most presenting site (55.6 %). Clinically positive lymph nodes were presented in 70.4 % of patients. Twenty patients (74.1 %) underwent sphincter sparing procedure. Pathological complete response (pCR) was achieved in seven patients (25.9 %). Tumor and nodal downstaging were recorded in (70.3 %) and (42.1 %) of patients, respectively. Acute and late toxicities were in acceptable range. Two-year disease-free survival was 70.2 %, and overall survival was 87.5 %. Induction FOLFOX followed by HFRT and concurrent 5-FU improves pCR in LARC, and this combination was feasible with acceptable toxicity. Further evaluations are mandatory for this new approach.

Autoamputation of rectum as a result of neoadjuvant radiotherapy: a case report

Total mesorectal excision and neoadjuvant radiotherapy have been known to reduce the local recurrence in advanced rectal carcinoma. Radiotherapy still exerts harmful side effects in spite of several advancements over the years. Bowels are most commonly affected organs. In some rare cases, rectum, colon and small bowel perforation, and septic complications have been reported in the course of, or after, neoadjuvant radiotherapy. We report here a case of rectal autoamputation due to the side effect of neoadjuvant radiotherapy.

Association between the cytogenetic profile of tumor cells and response to preoperative radiochemotherapy in locally advanced rectal cancer.

Neoadjuvant radiochemotherapy to locally advanced rectal carcinoma patients has proven efficient in a high percentage of cases. Despite this, some patients show nonresponse or even disease progression. Recent studies suggest that different genetic alterations may be associated with sensitivity versus resistance of rectal cancer tumor cells to neoadjuvant therapy. We investigated the relationship between intratumoral pathways of clonal evolution as assessed by interphase fluorescence in situ hybridization (51 different probes) and response to neoadjuvant radiochemotherapy, evaluated by Dworak criteria in 45 rectal cancer tumors before (n = 45) and after (n = 31) treatment. Losses of chromosomes 1p (44%), 8p (53%), 17p (47%), and 18q (38%) and gains of 1q (49%) and 13q (75%) as well as amplification of 8q (38%) and 20q (47%) chromosomal regions were those specific alterations found at higher frequencies. Significant association (P < 0.05) was found between alteration of 1p, 1q, 11p, 12p, and 17p chromosomal regions and degree of response to neoadjuvant therapy. A clear association was observed between cytogenetic profile of the ancestral tumor cell clone and response to radiochemotherapy; cases presenting with del(17p) showed a poor response to neoadjuvant treatment (P = 0.03), whereas presence of del(1p) was more frequently observed in responder patients (P = 0.0002). Moreover, a significantly higher number of copies of chromosomes 8q (P = 0.004), 13q (P = 0.003), and 20q (P = 0.002) were found after therapy versus paired pretreatment rectal cancer samples. Our results point out the existence of an association between tumor cytogenetics and response to neoadjuvant therapy in locally advanced rectal cancer. Further studies in larger series of patients are necessary to confirm our results.

75. Endoscopic sentinel node biopsy and axillary dissection for early breast cancer can be navigated by the fusion image of 3D-CT lymphography and SPECT-CT

75. Endoscopic sentinel node biopsy and axillary dissection for early breast cancer can be navigated by the fusion image of 3D-CT lymphography and SPECT-CT

74. GIST may have a higher incidence of second primary cancers which negatively impact upon survival

74. GIST may have a higher incidence of second primary cancers which negatively impact upon survival

Influence of preoperative chemoradiotherapy on changes of epidermal growth factor receptor expression in patients treated by preoperative chemoradiotherapy for local advanced rectal carcinoma

The aim of this retrospective study was to determine the prognostic impact of expression of epidermal growth factor receptor (EGFR) changes during neoadjuvant chemoradiotherapy in patients with locally advanced rectal adenocarcinoma. One hundred and three patients with locally advanced rectal adenocarcinoma of stage II and III were evaluated. All patients were administered the total dose of 44 -- 50.4 Gy. Concomitantly, the patients received capecitabine in the dose 825 mg/ m² in two daily oral administrations or 5- fluorouracil in the dose 200 mg/ m² in continuous infusion. Surgery was indicated at intervals of 4-8 weeks from chemoradiotherapy completion. EGFR expression in the pretreatment biopsies and in resected specimens was assessed with immunohistochemistry. All of 103 patients received radiotherapy without interruption up to the total planned dose. Downstaging was described in 64 patients. Six patients had complete pathologic remission. Recurrence occurred in 49 patients. Local recurrence was found in 22 patients, generalization of disease was reported in 27 patients. A total of 51 patients died. Increased EGFR expression was found in 26 patients. The statistically significantly shorter overall survival (p < 0.001) and disease-free survival (p < 0.001) was found in patients with increased expression of EGFR compared with patients where no increase in the expression of EGFR was observed during neoadjuvant chemoradiotherapy. The overexpression of EGFR during neoadjuvant chemoradiotherapy for locally advanced rectal adenocarcinoma is associated with significant shorter overall survival and disease-free survival.

Phase 2 Trial of Preoperative Chemoradiation Therapy With Oxaliplatin and Capecitabine for 137 Patients With Locally Advanced Rectal Carcinoma: Outcome and Failure Pattern

Phase 2 Trial of Preoperative Chemoradiation Therapy With Oxaliplatin and Capecitabine for 137 Patients With Locally Advanced Rectal Carcinoma: Outcome and Failure Pattern

Preoperative Image Guided Versus Conventional Pelvic Radiation Therapy for Locally Advanced Rectal Carcinoma: Comparison of Clinical Outcomes and Toxicity

Preoperative Image Guided Versus Conventional Pelvic Radiation Therapy for Locally Advanced Rectal Carcinoma: Comparison of Clinical Outcomes and Toxicity

Reduction in the size of enlarged pelvic lymph nodes after chemoradiation therapy is associated with fewer lymph node metastases in locally advanced rectal carcinoma.

We hypothesized that a reduction in the size of the lymph nodes after neoadjuvant therapy for locally advanced rectal carcinoma would be associated with decreased lymph node metastases and/or a better prognosis. Between March 2006 and April 2012, 71 patients with primary rectal cancer received neoadjuvant chemoradiation therapy (CRT). For all lymph nodes 5 mm or larger in size, the major and minor axes were measured on CT scan images, and the product was calculated. The lymph node size was determined before and after CRT. The patients were divided into three groups based on the lymph node size before and after treatment. Group A exhibited a reduction in size of 60% or more, Group B a reduction of less than 60% and Group C had no lymph node enlargement before treatment. The incidence of lymph node metastases on pathological examination was 15% in Group A and 50% in Group B (p = 0.006). The five-year disease-free survival in Group A was 84% compared with 78% in Group B (log rank p = 0.34). The five-year overall survival in Group A was 92% compared with 74% in Group B (log rank p = 0.088). A reduction in the size of enlarged lymph nodes after neoadjuvant therapy may be a useful prognostic factor for recurrence and survival.

A piece of my mind. The M&M game.

I am a physician who specializes in neonatology. There are few specialties more grounded in pure physiology. I am also a cancer patient. In the summer of 2010 I was diagnosed with a locally advanced rectal carcinoma. I received the best care medicine has to offer, from skilled and compassionate physicians: preoperative radiochemotherapy, a low anterior resection, a temporary ileostomy, and 12 cycles of chemotherapy. I worked throughout the entire ordeal and am told I “sailed through” chemo. I’ve made the mistake of reading tales of ghastly complications, misdiagnoses, and treatment failures on Internet chats devoted to my disease, and I know how lucky I am.

Pathological prognostic factors in locally advanced rectal carcinoma after neoadjuvant radiochemotherapy: analysis of 113 cases

Neoadjuvant radiochemotherapy (RCT) followed by surgical resection is the treatment for locally advanced mid-rectal or low rectal cancer. The aim of this study was to evaluate postoperative histological prognostic factors in a series of surgical specimens after neoadjuvant RCT. One hundred and thirteen patients were included. Macroscopic and microscopic examinations were performed according to CAP recommendations, with additional criteria such as tumour budding, the presence of calcifications, and response to neoadjuvant therapy assessed according to Modified Rectal Cancer Regression Grade (m-RCRG). The 3-year disease-free survival (DFS) was 67.6%. In univariate analysis, ypTN stage, tumour budding, circumferential margin, invaded margin and vascular and perineural invasion were prognostic factors. In multivariate analysis, the presence of calcifications (P=0.04) and an involved circumferential margin (P=0.03) were the only independent factors for worse DFS. mRCRG was not correlated with DFS. Among the 50 m-RCRG1 tumours, DFS was better in ypT0 patients than in other ypT stages (P=0.003). The presence of calcifications in the tumour bed is described for the first time as a prognostic factor in rectal cancer. The prognostic value of budding was demonstrated in this study after neoadjuvant RCT. ypT stage appears to be a more reliable predictor of oncological outcome than histological tumour regression grade, which needs to be standardized for better reproducibility.