Advanced Rectal Adenocarcinoma Research Articles

Does Fragmentation of Care in Locally Advanced Rectal Cancer Increase Patient Mortality?

ObjectiveTo evaluate health care fragmentation in patients with stage II and III rectal cancers. BackgroundFragmentation of care among multiple hospitals may worsen outcomes for cancer patients. MethodsNational Cancer Database was queried for adult patients who underwent radiation and surgery for locally advanced (stage II–III) rectal adenocarcinoma from 2006 to 2015. Fragmented care was defined as receiving radiation at a different hospital from surgery. Descriptive statistics characterized patients, and survival probability was plotted using the Kaplan-Meier method and a Cox proportional hazards model. ResultsA total of 37,081 patients underwent surgery and radiation for stage II–III rectal cancer from 2006 to 2015 (24,102 integrated care vs. 12,979 fragmented care). Patients who received fragmented care (hazard ratio [HR] 1.105; 95% CI 1.045–1.169) had a higher risk of mortality. Patients who received at least surgery (HR 0.84; 95% CI 0.77–0.92) at academic hospitals had a lower risk of mortality. Academic hospitals had a higher proportion of patients with fragmented care (38.0 vs. comprehensive community 32.8% vs. community 33.8%, p < 0.001). Within academic hospitals, fragmented care portended worse survival (integrated academic 80.0% vs. fragmented academic 76.7%, p = 0.0002). Fragmented care at academic hospitals had increased survival over integrated care at community hospitals (fragmented academic 76.7 vs. integrated community 72.2%, p = 0.00039). ConclusionsIn patients with stage II–III rectal cancer, patients who have integrated care at academic hospitals or at least surgery at academic centers had better survival. All efforts should be made to reduce care fragmentation and surgery at academic centers should be prioritized.

Racial Disparities in Treatment for Rectal Cancer at Minority-Serving Hospitals

BackgroundRacial disparities exist in patients with rectal cancer with respect to both treatment and survival. Minority-serving hospitals (MSHs) provide healthcare to a disproportionately large percent of minority patients in the USA. We examined the effects of rectal cancer treatment at MSH to understand drivers of these disparities. MethodsThe NCDB was queried (2004–2015), and patients diagnosed with stage II or III rectal adenocarcinoma were identified. Racial case mix distribution was calculated at the institutional level, and MSHs were defined as those within the top decile of Black and Hispanic patients. Logistic regression was used to identify predictors of receipt of standard of care treatment. Survival was assessed using the Kaplan-Meier method, and Cox proportional hazards models were used to evaluate adjusted risk of death. Analyses were clustered by facility. ResultsA total of 68,842 patients met the inclusion criteria. Of these patients, 63,242 (91.9%) were treated at non-MSH, and 5600 (8.1%) were treated at MSH. In multivariable analysis, treatment at MSH (OR 0.70 95%CI 0.61–0.80 p < 0.001) and Black race (OR 0.75 95%CI 0.70–0.81 p < 0.001) were associated with significantly lower odds of receiving standard of care. In adjusted analysis, Black patients had a significantly higher risk of mortality (HR 1.20 95%CI 1.14–1.26 p < 0.001). ConclusionsTreatment at MSH institutions and Black race were associated with significantly decreased odds of receipt of recommended standard therapy for locally advanced rectal adenocarcinoma. Survival was worse for Black patients compared to White patients despite adjustment for receipt of standard of care.

P-193 Safety, tolerability, and efficacy of total neoadjuvant therapy for adult patients with locally advanced high-risk rectal adenocarcinoma: Retrospective real-world data from South India

The treatment of locally advanced rectal adenocarcinoma with preoperative long-course chemoradiation (LCCRT) followed by TME has been established as a standard by prior studies. However, improvements in survival have plateaued due to an inability to deliver the planned adjuvant therapy. Total neoadjuvant therapy (TNT) has been developed to address this issue, but better patient selection is required to identify those who derive the most benefit from TNT. This retrospective cohort study evaluated TNT among a population of high-risk rectal adenocarcinoma patients selected on the basis of poor pathological and radiological parameters in a resource-limited setting.

Neoadjuvant Treatment in Upper Rectal Cancer Does Not Improve Oncologic Outcomes But Increases Postoperative Morbidity.

Neoadjuvant chemoradiation/radiation therapy in locally advanced (LA) upper rectal adenocarcinoma management remains unclear. The aim of this study was to compare outcomes between neoadjuvant chemoradiation therapy (CRT) and upfront surgery (US). A total of 127 patients were retrospectively included from 5 centers (79 treated with US and 48 with CRT). CRT and US groups were compared in terms of postoperative complications and long-term oncological and functional results. Total mesorectal excision (TME) was more frequent in CRT (58% vs. 20% in US, p<0.001). CRT was associated with more overall and severe postoperative complications (60% vs. 30%, p<0.001 and 17% vs. 1%, p=0.002, respectively), and was the only risk factor [OR=18.8 (2.2-160.2), p=0.007]. Five-year overall survival and 5-year recurrence-free survival were similar between CRT and US (96% vs. 91% p=0.256 and 85.4% vs. 85%, p=0.495). The functional results were similar between the two groups. CRT did not improve long-term oncological outcomes in patients with LA upper rectal adenocarcinoma, but increased postoperative complications compared with US.

A phase II study of induction PD-1 blockade in subjects with locally advanced mismatch repair-deficient rectal adenocarcinoma.

TPS4123 Background: The treatment of patients with locally advanced rectal cancer includes total neoadjuvant therapy with chemotherapy, chemoradiation followed by surgery. While most rectal cancers respond to combination induction chemotherapy, patients with mismatch repair deficient (dMMR) or MSI-H tumors have a significantly higher chance of progression with this treatment regimen. dMMR or MSI-H tumors have shown remarkable responses to PD-1 blockade, but the effect of neoadjuvant checkpoint inhibition has not been well studied. In this trial we will determine the pathologic complete response rate (pCR) of neoadjuvant anti-PD-1 blockade followed by standard chemoradiation in dMMR or MSI-H locally advanced rectal cancer. We hypothesize that treatment naïve dMMR or MSI-H rectal cancers will achieve a robust clinical response to PD-1 blockade and that the total neodjuvant therapy with PD-1 blockade followed by chemoradiation will improve pCR rates. Methods: Eligible patients ≥18 years of age with Stage II (T3-4, N-) or Stage III (any T, N+) histologically confirmed dMMR or MSI-H (by NGS) rectal adenocarcinoma will be enrolled. Patients will receive TSR-042 (500mg IV) every 3 weeks for a maximum of 8 cycles (6 months of treatment). Imaging, internal endoscopic exam and ctDNA blood draw will be performed at 6 weeks and every 3 months during induction anti-PD-1 treatment. Adverse events and surgical complications will be graded according to the NCI CTCAE v5 and the Clavien-Dindo classification, respectively. Following neoadjuvant checkpoint blockade, patients will undergo conventional chemoradiotherapy followed by surgical resection. The primary endpoint is pathologic complete response compared with historical control in pMMR patients. Patients will be followed up every 6 months for assessment of disease-free survival for up to five years. Clinical trial information: NCT04165772 .

Predicting Rectal Cancer Response to Neoadjuvant Chemoradiotherapy Using Deep Learning of Diffusion Kurtosis MRI.

Background Preoperative response evaluation with neoadjuvant chemoradiotherapy remains a challenge in the setting of locally advanced rectal cancer. Recently, deep learning (DL) has been widely used in tumor diagnosis and treatment and has produced exciting results. Purpose To develop and validate a DL method to predict response of rectal cancer to neoadjuvant therapy based on diffusion kurtosis and T2-weighted MRI. Materials and Methods In this prospective study, participants with locally advanced rectal adenocarcinoma (≥cT3 or N+) proved at histopathology and baseline MRI who were scheduled to undergo preoperative chemoradiotherapy were enrolled from October 2015 to December 2017 and were chronologically divided into 308 training samples and 104 test samples. DL models were constructed primarily to predict pathologic complete response (pCR) and secondarily to assess tumor regression grade (TRG) (TRG0 and TRG1 vs TRG2 and TRG3) and T downstaging. Other analysis included comparisons of diffusion kurtosis MRI parameters and subjective evaluation by radiologists. Results A total of 383 participants (mean age, 57 years ± 10 [standard deviation]; 229 men) were evaluated (290 in the training cohort, 93 in the test cohort). The area under the receiver operating characteristic curve (AUC) was 0.99 for the pCR model in the test cohort, which was higher than the AUC for raters 1 and 2 (0.66 and 0.72, respectively; P < .001 for both). AUC for the DL model was 0.70 for TRG and 0.79 for T downstaging. AUC for pCR with the DL model was better than AUC for the best-performing diffusion kurtosis MRI parameters alone (diffusion coefficient in normal diffusion after correcting the non-Gaussian effect [Dapp value] before neoadjuvant therapy, AUC = 0.76). Subjective evaluation by radiologists yielded a higher error rate (1 - accuracy) (25 of 93 [26.9%] and 23 of 93 [24.8%] for raters 1 and 2, respectively) in predicting pCR than did evaluation with the DL model (two of 93 [2.2%]); the radiologists achieved a lower error rate (12 of 93 [12.9%] and 13 of 93 [14.0%] for raters 1 and 2, respectively) when assisted by the DL model. Conclusion A deep learning model based on diffusion kurtosis MRI showed good performance for predicting pathologic complete response and aided the radiologist in assessing response of locally advanced rectal cancer after neoadjuvant chemoradiotherapy. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Koh in this issue.

Diffusion-weighted magnetic resonance imaging of mucin pools in locally advanced rectal mucinous adenocarcinoma predicts tumor response to neoadjuvant therapy

PurposeTo determine the prognostic value of diffusion-weighted magnetic resonance imaging (DW-MRI) of mucin pools (MPs) in predicting the response of patients with locally advanced rectal mucinous adenocarcinoma (RMAC) to neoadjuvant therapy (NAT). MethodA total of 59 patients with histologically proven RMAC received NAT before applying total mesorectal excision. MP and solid tumor (ST) components were identified using T2 weighted image (T2WI) and DW-MRI, and apparent diffusion coefficient (ADC) values were calculated prior, during and after NAT. The receiver operating characteristic (ROC) curve was used to evaluate the ability of ADC values in predicting NAT efficacy as determined by post-pathological tumor regression grade (TRG). In addition, radiologists evaluated the TNM staging of tumors, the mesorectal fascia invasion, the maximal tumor length, and the distance from the inferior part of the tumor to the anal verge. Multivariate analysis and logistic regression were used to determine the correlation of ADC values and baseline MRI parameters with NAT efficacy. ResultsAmong the 59 patients, 44 (74.6 %) were men. The mean age of patients was 49.5 ± 11.2 years. The mean ΔADC value during NAT obtained on mucus pool was higher in the responsiveness group than that of the nonresponsiveness group (0.506 ± 0.342 vs. 0.053 ± 0.240 × 10−3 mm2/s, P < .001), with an area under the curve of receiver operating characteristic of 0.881 (95 %CI, 0.770–0.951). ConclusionsMRI can be reliably used to measure MP-ADC, which as we showed in this study, represents a biomarker to predict tumor responsiveness of NAT in RMAC patients.

Development of a long non-coding RNA signature for prediction of response to neoadjuvant chemoradiotherapy in locally advanced rectal adenocarcinoma.

Standard treatment for locally advanced rectal adenocarcinoma (LARC) includes a combination of chemotherapy with pyrimidine analogues, such as capecitabine, and radiation therapy, followed by surgery. Currently no clinically useful genomic predictors of benefit from neoadjuvant chemoradiotherapy (nCRT) exist for LARC. In this study we assessed the expression of 8,127 long noncoding RNAs (lncRNAs), poorly studied in LARC, to infer their ability in classifying patients’ pathological complete response (pCR). We collected and analyzed, using lncRNA-specific Agilent microarrays a consecutive series of 61 LARC cases undergoing nCRT. Potential lncRNA predictors in responders and non-responders to nCRT were identified with LASSO regression, and a model was optimized using k-fold cross-validation after selection of the three most informative lncRNA. 11 lncRNAs were differentially expressed with false discovery rate < 0.01 between responders and non-responders to NACT. We identified lnc-KLF7-1, lnc-MAB21L2-1, and LINC00324 as the most promising variable subset for classification building. Overall sensitivity and specificity were 0.91 and 0.94 respectively, with an AUC of our ROC curve = 0.93. Our study shows for the first time that lncRNAs can accurately predict response in LARC undergoing nCRT. Our three-lncRNA based signature must be independently validated and further analyses must be conducted to fully understand the biological role of the identified signature, but our results suggest lncRNAs may be an ideal biomarker for response prediction in the studied setting.

Short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma.

139 Background: Total neoadjuvant treatment (TNT) for locally advanced rectal cancer is becoming an accepted approach over the last few years with increasing pathologic complete response (pCR) and compliance of patients for chemotherapy in comparison with the current standard of care i.e., fluoropyrimidine based chemoradiation followed by surgery and adjuvant chemotherapy. Sequential use checkpoint inhibitors after radiation therapy (RT) has demonstrated synergistic effect in vivo leading to decrease in size of irradiated and non-irradiated secondary tumors outside the radiation field (abscopal effect). Methods: This is an investigator initiated; open-label, single-arm multicenter phase II study, adopting Simon’s two-stage aiming at evaluating the pCR rate and safety of using short-course radiation therapy (25 Grays in 5 fractions), followed by 6 cycles of mFOLFOX-6 plus Avelumab (anti PDL1), then total mesorectal excision(TME) in patients with locally-advanced, potentially resectable rectal adenocarcinoma. Results: 13 out of 44 patients were accrued from 20, July till 28, Dec 2018 in the first stage of the study (30% from total sample size). They all met the inclusion criteria and received full protocol treatment. 12 out of the 13 completed TME. 1 of the 13 had progression of disease, so surgery was aborted and patient was dropped out the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33.0, 73.0) years. The first interim analysis revealed 3 patients (25%) achieved pCR (tumor regression grade: TRG = 0) out of 12 as compared to the historical control group with pCR of 16%. For the rest of the patients, 3 (25%) had major pathologic response rate (pRR) with TRG = 1 (&lt; 10% viable cells is tumor bed).In total, 6 out of 12 patients (50%) had major pathologic response rate. As for safety, no serious adverse events of grade 3 and 4 were reported. Conclusions: Based on the first interim analysis results, incorporation of Avelumab and short course radiotherapy is tolerable in patients with locally advanced rectal cancer treated with TNT. The study will resume recruitment to reach the target accrual. Clinical trial information: NCT03503630.

Phase I study of preoperative capecitabine and lenvatinib with external radiation therapy in locally advanced rectal adenocarcinoma.

125 Background: Neoadjuvant chemo-radiation is a standard of care for locally advanced rectal cancer. Patients with pathologic complete response (pCR) have improved outcomes with less local and systemic failure. Dual targeting with platelet derived growth factor (PDGF) and vascular endothelial growth factor receptor (VEGFR) in combination with radiation can escalate tumor response with radiation. Lenvatinib is an oral multi-kinase inhibitor and had shown potent anti-tumor activity in xenograft models cultured with human colorectal cancer (CRC) lines. Methods: Patients with stage II or III rectal cancer, confirmed by endoscopic ultrasound or MRI, were recruited in 3 cohorts of 3 patients per dose level, with an expansion cohort at the MTD. Lenvatinib oral daily dose started at 14 mg (cohort 1) and was escalated to 20 mg (cohort 2) followed by 24 mg (cohort 3). In this 3+3 design, patients received dose escalation of lenvatinib with standard doses of capecitabine (850 mg/m2 PO BID) concurrent with external beam radiation on days 1-5 weekly for 28 treatments. Following completion patients underwent surgery in 6-10 weeks. Results: Twenty patients with median age of 55 were enrolled in 3 cohorts (1 patient was ineligible). There were no dose limiting toxicity at the maximum tested dose of lenvatinib (24 mg). Two patients are still awaiting surgery. 12 patients have undergone low anterior resection and 5 patients have had abdominoperineal resection. Therefore, out of 17 patients, 29.4% (5/17) showed pCR, and downstaging was observed in 71% of the patients (12/17). The mean neoadjuvant rectal cancer score (NAR) was 11.4 and median NAR was 8.43. Six patients had grade 3 adverse events (AEs) (1 rectal pain,1 transaminitis, 2 lymphopenia, 1 HTN, 1 with both leukocytosis and hyponatremia). No grade 4 AEs were noted. Most common AEs were hypertension, rectal pain, nausea, diarrhea, fatigue and dermatitis. No peri operative complications were observed. Conclusions: The study shows that the combination of lenvatinib and capecitabine with radiation is well tolerated in locally advanced rectal cancer with promising mean NAR score. The encouraging results will need to be validated in a randomized study. Clinical trial information: NCT02935309.

The role of restaging MRI post neoadjuvant therapy for locoregionally advanced rectal cancer

Background: Rectal cancer management has evolved from surgery to neoadjuvant radiotherapy to total chemoradiotherapy regimens. Magnetic resonance imaging (MRI) is the gold standard for staging; however, its role for assessing response to neoadjuvant therapy is less than clear. Objective: To assess the role of restaging MRI post neoadjuvant long-course chemoradiotherapy (NA CRT) for locoregionally advanced rectal cancer. Design: A retrospective audit of prospectively collected data. Setting: A tertiary hospital colorectal unit. Patients and Methods: Patients with locoregionally advanced rectal adenocarcinoma (T3/T4 and/or nodal disease), who underwent restaging pelvic MRI scans post-NA CRT were included. Medical records of relevant radiology and operative histopathology were reviewed. Main Outcome Measures: To determine whether restaging MRI altered subsequent patient management (compared to the initial plan as documented in the pretreatment colorectal multidisciplinary team meeting). Sample Size: Twenty-three patients with restaging MRI. Results: On diagnosis, 15 patients (65.2%) had American Joint Committee on Cancer (AJCC) stage-III disease; two patients had AJCC stage-II disease (8.7%), and five patients (21.7%) had AJCC stage-IV disease with limited metastases (curative intent to treatment). Three patients had a complete clinical response (cCR) post NA CRT. Fourteen tumors had downstaging (MRI tumor regression grade 2-3, 58.3%). In three patients (13.0%), restaging MRI altered patient management. Two of them had extensive disease that underwent significant downstaging, enabling avoidance of a pelvic exenteration; and one also had sufficient downstaging and was able to have a sphincter preserving operation as a result. Conclusions: MRI may have a role in patients with the extensive locoregional disease or in ultralow rectal cancers where it is unclear if sphincter preservation is possible. Limitations: Small sample size; additionally, “watch and wait” methods are not routinely practiced in this tertiary unit. Conflict of Interest: None.

Predicting prognosis according to preoperative chemotherapy response in patients with locally advanced lower rectal cancer

BackgroundNeoadjuvant chemoradiotherapy is regarded as the standard of treatment for locally advanced lower rectal cancer, although some of these cases are systemic, and distant control may be inadequate. Neoadjuvant chemotherapy could compensate for such shortcomings, potentially yielding better survival outcomes. We aimed to stratify patients into prognostic groups on the basis of preoperative factors, including response to neoadjuvant chemotherapy.MethodsWe retrospectively analyzed patients with locally advanced lower rectal adenocarcinoma (clinical stage II/III with high-risk features of distant metastasis) who were treated with neoadjuvant chemotherapy (without radiotherapy) followed by curative resection between 2010 and 2017. Reduction in tumor volume (before vs. after neoadjuvant chemotherapy) was measured using magnetic resonance imaging, and a reduction above 60% was defined as a good response. Recurrence and overall survival were evaluated.ResultsThe cohort comprised 102 patients. Good response to neoadjuvant chemotherapy was associated with better 5-year recurrence-free survival (good responders: 81.1%, poor responders: 49.0%; p = 0.001) and 5-year overall survival (good responders: 94.9%, poor responders: 80.6%; p = 0.06). In a multivariate analysis, extramural venous invasion on magnetic resonance imaging after neoadjuvant chemotherapy and a tumor volume reduction rate < 60 were found to be significantly and independently associated with worse recurrence-free survival (hazard ratio: 2.74, 95% confidence interval: 1.36–5.50, p = 0.005 and hazard ratio: 3.48, 95% confidence interval: 1.57–7.72, p = 0.002, respectively). Good responders without extramural venous invasion had the best 5-year recurrence-free and overall survival (89.0 and 93.8%, respectively). Poor responders with extramural venous invasion had the worst 5-year recurrence-free and overall survival (21.4 and 50.0%, respectively).ConclusionsReductions in tumor volume after neoadjuvant chemotherapy were associated with a better prognosis in patients with locally advanced lower rectal cancer. Extramural venous invasion was a preoperative prognostic factor.

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.

Local excision in rectal cancer patients with major or complete clinical response after neoadjuvant therapy: a case-matched study.

To assess the long-term oncological outcomes in patients with locally advanced rectal cancer who underwent neoadjuvant therapy followed by local or total mesorectal excision. Patients with locally advanced rectal adenocarcinoma who received neoadjuvant therapy from 2005 to 2017 were evaluated. Those with major or complete clinical response underwent a full-thickness local excision. Kaplan-Meier estimates were used to evaluate overall, disease-free, and local recurrence-free survival of patients who underwent local excision (LE group) and were compared with a matched cohort of patients who underwent total mesorectal excision (TME group). Among 252 patients who received neoadjuvant therapy for rectal cancer, 51 (20.2%) underwent a local excision. At a median follow-up of 61months, patients who underwent local excision were stoma-free in 88.2% of cases and with rectum preserved in 78.5% of cases, respectively. The estimated 5-year local, disease-free, and overall survival was 91.8% vs 97.6% (95% CI: 79.5-96.8 vs 84.6-99.6), 86.7% vs 86.4% (95% CI: 72.5-93.9 vs 70.1-94.1), and 85% vs 90% (95% CI: 69.0-93.0% vs 75.3-96.2), in the study and matched control group, respectively. None of the differences was statistically significant. One-fifth of patients with locally advanced rectal cancer are manageable with a rectum-sparing approach after neoadjuvant therapy. With this strategy, about 80% patients will have their rectum preserved and 90% will be without stoma at long term.

Phase II Randomized Multi-center Trial of Total Neoadjuvant Therapy With and Without CD40 Agonist, APX005M, for Locally Advanced Rectal Adenocarcinoma

Phase II Randomized Multi-center Trial of Total Neoadjuvant Therapy With and Without CD40 Agonist, APX005M, for Locally Advanced Rectal Adenocarcinoma

546P - Differential of the nutritional index before and after neoadjuvant chemoradiotherapy as a prognostic factor of recurrence in patients with locally advanced adenocarcinoma of the rectum

BackgroundThe Nutritional Prognostic Index (INP) is a nutritional and immunological marker. The difference between concomitant pre and post chemoradiotherapy INP and its impact as a prognostic factor for recurrence in patients with locally advanced rectal adenocarcinoma remains unclear. With the aim of providing greater evidence of the recurrent prognostic role of the differential of the pre and post INP in patients with locally advanced rectal adenocarcinoma we carried out the present study. MethodsOf the total of 206 patients, 74 patients were excluded. The analysis included 132 patients. INP formula: 10 * serum albumin (g / dL) + 0.005 * total lymphocyte count (per mm3). The INP values were determined in 2 points: before QT/RTneoadjuvant (preQT/RT INP ) and after the neoadjuvant QT/RT termination, (postQT/RT PNI). The difference in INP (dINP) was calculated with the formula: preQT/RT INP - postQT/RT INP. ResultsTable546P Univariate and multivariate analysisTableUnivariateMultivariateFactorPHRIC 95%PGender0.3761.4090.657 – 3.020.378Age0.0370.9690.940 – 0.9980.039body mass index0.0750.6340.382 – 1.0520.078Degree Differentiation0.3561.1790.697 – 2.020.550ypT0.1521.10.646 – 1.920.697ypN0.1021.280.947 – 1.750.106Diferencial INP0.1211.420.906 – 2.230.126ECOG0.0083.41.26 – 9.60.016In the Kaplan and meier analysis, recurrence free survival (SLR) was P=0.03. Independent factors for recurrence were age and ECOG (95% CI 0.940 – 0.998¸ P=0.037, HR 3.4 95% IC 1.26 – 9.6, P=0.016). Our findings showed a better SLR in the low dINP subgroup, so we took it as a cutoff 5. Patients who presented a dINP less than 5, have a better SLR in relation to those who have a dINP > 5. P=0.013. ConclusionsThe difference less than 5 between the nutritional index before and after neoadjuvant chemoradiotherapy in patients with locally advanced adenocarcinoma of the rectum is associated with an increase in SLR as an independent predictor of recurrence. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

A Retrospective Analysis Comparing Outcomes Following Total Neoadjuvant Therapy and Following Neoadjuvant Chemoradiation Therapy in Patients with Locally Advanced Rectal Cancer

To compare outcomes following Total Neoadjuvant Therapy (TNT) and following neoadjuvant chemoradiation therapy (nCRT) with or without adjuvant chemotherapy in patients with locally advanced rectal adenocarcinoma (LARC), defined as T3/4 or node positive disease, using the National Cancer Database. We identified LARC patients diagnosed between 2004 and 2015 who received chemotherapy and radiotherapy (RT) preoperatively and definitive surgery within one year of RT. Patients were considered to have received TNT if multiagent chemotherapy was given ≥2 months before RT and no adjuvant chemotherapy was given. Patients were considered to have received neoadjuvant chemoradiation therapy (nCRT) if preoperative RT and chemotherapy were started within 2 weeks from each other. A 2:1 propensity match was performed to account for selection bias, adjusting for age, gender, diagnosis year, race, comorbidity score, cT, cN, grade, facility type, urban status, insurance, and income. Kaplan-Meier survival analysis with log-rank test was used to compare overall survival (OS). Multivariable Cox regression modeling was performed to determine factors associated with OS. Multivariable logistic regression modeling was used to determine if TNT is associated with pathological complete response (pCR), defined as ypT0N0, and negative circumferential resection margin (CRM). After propensity matching, 372 patients receiving TNT were paired with 707 patients receiving nCRT. In the matched cohort, the median follow-up time was 31.0 months for TNT and 33.7 months for nCRT. Median time to surgery was 8.4 months (IQR: 7.2 to 9.2 months) for TNT compared to 4.4 months (IQR: 3.9 to 5.2 months) for nCRT. OS for TNT was similar to nCRT in both the matched (log-rank p=0.15) and the unmatched cohort (log-rank p=0.85). The 3- and 5-year OS rates for TNT vs. nCRT in the matched cohort were 88.5% vs. 88.9% and 73.6% vs. 78.5%, respectively (p>0.2 for both years). The multivariable analysis showed no significant difference in OS between TNT and nCRT (matched cohort: HR=1.21, 95%CI 0.87-1.69, p=0.25; unmatched cohort: HR=1.17, 95%CI: 0.90-1.51, p=0.24). Sensitivity analysis with 10:1 propensity matching for improved statistical power showed similar OS between TNT and nCRT (HR=1.16, 95% CI: 0.88-1.53, p=0.28). The pCR and negative CRM rates with TNT and nCRT were 16.9% vs. 13.1% (p=0.12) and 95.3% vs. 93.1% (p=0.30), respectively. TNT was not found to be significantly associated with pCR (OR=1.36, p=0.13) or negative CRM (OR=1.77, p=0.19) in multivariable logistic regression modeling. With results from current clinical trials pending, our data suggested that TNT and nCRT resulted in similar survival, while TNT led to higher pCR and CRM negative rate, albeit not statistically significant.

Sequential short-course radiation therapy and chemotherapy in the neoadjuvant treatment of rectal adenocarcinoma

BackgroundThere is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas. We report our single-institution experience of feasibility and early oncologic outcomes of short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by consolidation neoadjuvant chemotherapy.MethodsWe reviewed the records of 26 patients with locally advanced rectal adenocarcinoma. All patients underwent short course radiotherapy (5 Gy X 5 fractions) followed by chemotherapy [either modified infusional and bolus 5-fluorouracail and oxalipatin (mFOLFOX6) or capecitabine and oxaliplatin] prior to consideration for surgery. A full course of chemotherapy was defined as at least 8 weeks of chemotherapy.ResultsThere were five clinical (c) T2, 16 cT3, and five cT4 rectal tumors, with 88% cN+. Twenty-five patients received a median of 4 cycles (range 3 to 8) of mFOLFOX6 (with one cycle defined as a two-week period); one patient received 3 cycles of capecitabine and oxaliplatin. All patients completed SCRT; 81% completed the full course of neoadjuvant chemotherapy with 19% requiring dose reductions in chemotherapy, most commonly due to neuropathy. Nineteen patients underwent post-treatment endoscopic evaluation, and nine patients were noted to achieve a complete clinical response (CCR). Six of the nine patients who achieved CCR opted for a non-operative approach of watch-and-wait. Twenty patients underwent surgical resection; pathologic complete response was observed in seven (35%) of these twenty. The main radiation-associated toxicity was proctitis with CTCAE Grade 2 proctitis observed in seven patients (27%). Post-operative Clavien-Dindo Grade 3 complications within 30 days of surgery were identified in six patients (30%), with no Grade 4 or 5 adverse events. Median length of hospital stay was 4.5 days (range 2–16 days); three patients were readmitted within a 30 day period.ConclusionsShort course preoperative radiotherapy followed by neoadjuvant chemotherapy was well-tolerated and achieved oncologic outcomes that compare favorably with short-course radiation therapy alone or long-course chemoradiotherapy. This regimen is associated with high rates of clinical and pathologic complete response.

Medical Therapy Optimization of Advanced Heart Failure in a Cancer Patient: When to Quit?

Introduction In CHF patients, medical therapy optimization (MTO) remains the mainstay of management. However, attaining MTO can be challenging in patients with advanced CHF due to their symptomatic and hemodynamic intolerance. We present a case of a patient with advanced CHF and rectal cancer in whom slowly cautious MTO succeeded in improving cardiac function and candidacy for cancer chemotherapy and surgery. Case A 57-year-old male with a medical history of advanced nonischemic CHF (EF 10-15%), a-fib, and rectal well-differentiated adenocarcinoma stage IIA (diagnosed 1 month ago) with GI bleeding and defecation pain presented with dyspnea on minimal exertion and orthopnea. He also had dizziness with standing due to symptomatic hypotension. SBP was between 100-115 mmHg. MRI pelvis showed T3 rectal mass with no enlargement of lymph nodes. Further imaging showed no distant metastases. Due to his advanced CHF, the patient was considered at high risk for surgery or chemotherapy. Rectal palliative radiation therapy was performed. He agreed on hospice palliative care for symptomatic relief. From Cardiology stand of point, the decision was made to continue MTO aiming for myocardial recovery. Radical adjustment of regimen and initiation of medications at miniscule doses eventually led to myocardial recovery with EF of 51% (figure 1). Patient's SOB and dizziness improved. Cancer progressed to stage IIIb. Due to his improvement, the patient became at lower cardiac risk for other cancer therapy options. As a result, Oncology plan changed to proceed with FOLFOX (5-FU/ Leucovorin/ Oxaliplatin) chemotherapy and surgery. Discussion In our patient, advanced therapy with left ventricular assist device was not possible given his risk of worsening GI bleeding on anticoagulation. Heart transplantation was not an option given the risk of cancer progression on immunosuppressive therapy. In the context of the patient's condition and comorbidities, the best option left was to proceed with cautious MTO with clinical and hemodynamic monitoring. MTO resulted in clinical and cardiac function improvement. This gave the patient the window to become a candidate for other cancer therapy options that were not available for him before. Conclusion Medical therapy optimization in all patients with CHF should always be sought. Despite being challenging under certain circumstances, as seen in our patient, slow and cautious MTO can eventually result in significant improvement in clinical status, cardiac function, and candidacy for other therapy options for other comorbidities.

Clinical outcomes of preoperative chemoradiotherapy in octogenarian with locally advanced rectal cancer.

The number of elderly patients who receive surgical treatment for rectal cancer has gradually increased with aging of the population. In recent years, preoperative chemoradiotherapy, followed by surgical treatment, has been widely used for treating patients with locally advanced rectal adenocarcinoma. The aim of the present study was to evaluate if preoperative chemoradiotherapy is efficacious and safe for the treatment of rectal cancer in patients older than 80 years. A total of 293 patients with rectal cancer, who received preoperative chemoradiotherapy from 2007 to 2017, were studied. Comorbidities and the short- and long-term outcomes in elderly patients (aged ≥80 years old) were investigated and compared to younger patients. The elderly group comprised of 17 patients (5.8%). Pulmonary disease was the most common comorbidity (23.5%). No significant difference between the two groups regarding the rate of completeness of chemoradiotherapy was detected (P=0.26). Curative resection was performed in 14 patients in the elderly group and 252 patients in the younger group. Among 7 patients from both groups who could not receive curative resection due to their poor general condition, 4 patients had decreased lower respiratory function due to pneumonia (3 patients) or chronic obstructive pulmonary disease (1 patient). Morbidity and mortality rates were similar in elderly and younger groups (35.7% vs. 27.0%, 0% vs. 0%, respectively; P=0.54, P=1.00). No significant difference was found regarding recurrence between the two groups (P=1.00). To conclude, preoperative chemoradiotherapy in elderly patients with rectal cancer is safe and well tolerated.