Long-term clinical outcomes of [177Lu]Lu-DOTATATE in patients with metastatic neuroendocrine tumors.

The incidence of gastroenteropancreatic neuroendocrine tumors has been rising and these tumors are usually only diagnosed at a metastatic stage. Present first line treatments include somatostatin analogs, targeted therapies and peptide receptor radionuclide therapy. The Lutetium-177 [177Lu] based radiotracer [177Lu]Lu-DOTATATE has only been approved as first-line treatment of metastatic midgut NETs however its efficacy as a third line or above treatment in patients with non ileal primaries has not been tested. In our study, we identified 25 patients with histologically confirmed well-differentiated metastatic neuroendocrine tumors and administered [177Lu]Lu-DOTATATE as a second line, third line and fourth line treatment. Our study demonstrated a notable response in patients with non-ileal primaries and heavily pretreated disease, warranting further studies for additional cycles of treatment.

Targeted Therapy for BRAF V600E Positive Pancreatic Adenocarcinoma: Two Case Reports.

BACKGROUND/AIM: Pancreatic ductal adenocarcinoma (PDAC) is a malignancy that typically portends a poor prognosis, with a median overall survival ranging from eight to twelve months in patients with metastatic disease. Novel modalities of therapy, primarily targeted therapy, are now considered for patients with targetable mutations, such as BRAF mutations based on next generation sequencing. BRAF mutations specifically within pancreatic adenocarcinoma remain rare with an incidence of approximately 3%. Previous research on BRAF mutated pancreatic adenocarcinoma is extremely scarce, limited primarily to case reports; therefore, little is known regarding this entity. CASE REPORT: We seek to contribute to prior literature with the presentation of two cases of patients with BRAF V600E + pancreatic adenocarcinoma, who did not have a favorable response to initial systemic chemotherapy and were both subsequently treated with targeted therapy (dabrafenib and trametinib). Each of the patients has sustained a favorable response and there is no evidence of progression thus far on dabrafenib and trametinib, highlighting the potential benefit of targeted therapy in these patients. CONCLUSION: These cases emphasize the importance of early next generation sequencing and the consideration of BRAF targeted treatment in this patient population, especially if a response to initial chemotherapy is not sustained.

Prophylactic Anticoagulation in Patients With Pancreatic Adenocarcinoma: A Single Tertiary Care Center Retrospective QI Project.

BACKGROUND/AIM: A well-known complication of pancreatic adenocarcinoma (PDAC) is venous thromboembolism (VTE). The Khorana score is used as a tool to help determine the role of primary prophylaxis (PPx) in cancer patients with VTE. This study compared outcomes in PDAC patients who received primary PPx (anticoagulation) versus those who did not. PATIENTS AND METHODS: PDAC patients from 2017-2019 at Allegheny General Hospital were retrospectively reviewed. Descriptive statistics were presented via medians with interquartile ranges for continuous variables and percentages for categorical variables. Predictors of VTE development were determined using univariable and multivariable logistic regression models. T-tests and Chi-square tests were used to compare means and percentages, respectively. RESULTS: A total of 102 patients with full VTE PPx data were reviewed. At least one VTE event was identified in 29 patients (28.2%). A total of 4 out of these 29 patients (13.8%) were on PPx anticoagulation. Death secondary to VTE occurred in one patient without PPx. Two (2.0%) patients experienced bleeding events of those prescribed VTE PPx. On univariable analysis, stage IV disease, planned surgery, and unresectable disease were predictors of VTE development. On multivariate analysis, total pancreatectomy was a predictor of VTE development. There was no difference in average time to progression amongst patients who had developed VTE versus those who did not. CONCLUSION: The Khorana score for VTE PPx in PDAC patients in underutilized.

A randomized, phase II trial of oral azacitidine (CC-486) in patients with resected pancreatic adenocarcinoma at high risk for recurrence.

BACKGROUND: Of the only 20% of patients with resectable pancreatic ductal adenocarcinoma (rPDA), cancer recurs in 80% of cases. Epigenetic dysregulation is an early hallmark of cancer cells acquiring metastatic potential, and epigenetic modulators may reactivate tumor suppressor genes, delay recurrence, and sensitize PDA to future chemotherapy. METHODS: This was a randomized phase II study (NCT01845805) of CC-486 (oral DNA methyltransferase inhibitor azacitidine) vs. observation (OBS) in rPDA patients harboring high-risk features (stage pN1-2, R1 margins, or elevated CA 19-9 level) with no evidence of disease following standard adjuvant therapy. Patients were randomized to oral CC-486 treatment (300 mg daily on days 1-21 on a 28-day cycle) or OBS for up to 12 cycles or until disease relapse/unacceptable toxicities. Following recurrence, records of next-line therapies, imaging, and survival were obtained. The primary endpoint was progression-free survival (PFS)-time from randomization to recurrence (imaging/biopsy confirmed or death). Secondary endpoints included OS and PFS and ORR and metastatic PFS with subsequent next-line systemic therapy in metastatic setting. RESULTS: Forty-nine patients (24 in CC-486 arm, 25 in OBS arm) were randomized: median age 66 (range 36-81), 53% male, 73% node positive, 49% elevated CA 19-9, 20% R1 resection, 63% and 100% received perioperative concurrent chemoradiation and chemotherapy, respectively. Median time from surgery to randomization was 9.6 mo (range 2.9-36.8). For the CC-486 arm, median treatment duration was 5.6 mo (range 1.3 to 12.8) with 14 treatment-related grade 3 or 4 AEs among 5 patients (22%) resulting in dose-reduction. Four patients (17%) discontinued therapy due to AEs. With median follow-up of 20.3mo (IQR 12.8, 41.4), 38 (79%) of evaluable patients recurred (34 imaging-confirmed, 4 clinically). Median PFS in imagining-confirmed cases was 9.2 and 8.9mo (HR 0.94, 95% CI 0.46-1.87, p = 0.85) for CC-486 and OBS patients, respectively. Median OS (2-yr OS%) was 33.8 (50%) and 26.4 mo (61%) in CC-486 and OBS patients, respectively. (HR 0.98, 95% CI 0.46-2.05, p = 0.96). ORR with subsequent chemotherapy in the metastatic setting was minimal in both arms. CONCLUSIONS: Treatment with CC-486 following adjuvant therapy did not prolong time-to-relapse in patients with high-risk rPDA or improve disease response on 1st-line metastatic therapy.

Rechallenging Fluoropyrimidine-Induced Cardiotoxicity and Neurotoxicity: A Report of Two Cases.

Fluoropyrimidines (FP's) such as fluorouracil (5-FU) and capecitabine are antimetabolites widely used in many solid tumors. FPs side effects are caused mainly by a lack of dihydropyrimidine dehydrogenase (DPD) enzyme. It has been noticed that treatment with infusional regimens of 5-FU is associated with more adverse events (AE) compared to bolus forms. Here, we report two cases of unusual side effects seen with infusional 5-FU and capecitabine and how early intervention by withholding ongoing treatment can help in preventing progression and mortality.

The prognostic value of KRAS mutation in locally advanced rectal cancer.

BACKGROUND: The prognostic value of the KRAS proto-oncogene mutation in colorectal cancer has been debated. Herein, we analyzed the National Cancer Database (NCDB) to assess the role of KRAS mutation as a prognostic marker in patients with locally advanced rectal cancer (LARC). METHODS: We identified LARC patients treated with neoadjuvant chemoradiation from 2004-2015 excluding those with stage I/IV disease and unknown KRAS status. Multivariable logistic regression identified variables associated with KRAS positivity. Propensity adjusted univariable and multivariable analyses identified predictors of survival. RESULTS: Of the 784 eligible patients, 506 were KRAS-negative (KRAS -) and 278 were KRAS-positive (KRAS +). Median survival was 63.6 months and 76.3 months for KRAS + and KRAS - patients respectively, with propensity adjusted 3 and 5-year survival of 79.9% vs. 83.6% and 56.7% vs. 61.9% respectively (HR 1.56, p 1.074-2.272). Male sex, no insurance, and KRAS + disease were associated with poorer survival on unadjusted and propensity adjusted multivariable analyses. CONCLUSIONS: Our analysis of KRAS + LARC suggest that KRAS + disease is associated with poorer overall survival. Given the inherent limitations of retrospective data, prospective validation is warranted.

Incidence of hypersensitivity reactions in patients on H1-receptor antagonists receiving oxaliplatin-based chemotherapy.

OBJECTIVE: This study determined the incidence of hypersensitivity reactions in patients receiving oxaliplatin-based chemotherapy while on H1-receptor antagonists (H1RAs). Prophylaxis for patients receiving oxaliplatin is not currently recommended. H1RAs are used for the treatment of reactions; however, prophylactic H1RAs have not been well-studied. METHODS: This retrospective chart review included patients with solid tumor malignancies who received H1RAs while on oxaliplatin-based chemotherapy between August 1, 2016 and October 31, 2019. RESULTS: Of fifty-one patients, there were four hypersensitivity reactions (8%), most of which were mild, occurred within 60 minutes of the start of the infusion, and did not result in an interruption in treatment. One severe reaction occurred, which required discontinuation of therapy. Forty-two patients (82%) were able to receive at least 9 cycles of oxaliplatin without a reported reaction. CONCLUSION: In this observational study, the incidence rate of hypersensitivity reactions in patients receiving oxaliplatin while on H1RAs was lower than reported in previous literature. Most reactions were mild, and patients were able to continue oxaliplatin-based therapy. With future, randomized controlled trials, H1RAs may prove to be effective in preventing or delaying the onset of hypersensitivity reactions related to oxaliplatin.

A Curious Case of a Posterior Mediastinal Mass.

Gastrointestinal stromal cell tumors (GISTs) are mesenchymal stromal tumors that are characteristically CD117 positive. Distinction from other spindle cell tumors such as leiomyomas and leiomyosarcomas is based on clinical, histological, and molecular features. Endoscopic ultrasonography-guided fine-needle aspiration has become a highly used means of preoperative identification of GIST, especially if immunohistochemical staining for CD117 can be performed. We present a case of a posterior mediastinal mass diagnosed as GIST after being found to be CD117 positive, later found to be a metastatic leiomyosarcoma.

Chemotherapy use in early stage anal canal squamous cell carcinoma and its impact on long-term overall survival,,.

BACKGROUND: The standard of care for non-metastatic squamous cell carcinoma of the anal canal (SCCA) is concurrent chemoradiotherapy. It is postulated that chemotherapy could be omitted for the earliest stages without worsening outcomes. METHODS: We queried the NCDB from 2004-2016 for patients with cT1N0M0 SCCA treated non-operatively with radiation, with and without chemotherapy, and at least two months of follow-up. Of the 2,959 patients meeting eligibility, 92% received chemotherapy (n = 2722) and 8% (n = 237) did not. Most patients were white (n = 2676), female (n = 2019), had private insurance (n = 1507) and were treated in a comprehensive cancer center (n = 1389). Average age was 58.5 years. RESULTS: Predictors of chemotherapy omission were age > 58 years (OR 0.66, 95% CI [0.49-0.90], P = 0.0087), higher comorbidity score (OR 0.62, 95% CI [0.38-0.99], P = 0.0442), African American race (OR 0.57, 95% CI [0.36-0.90], P = 0.0156) and treatment at the start of the study period (OR 1 for years 2004-2006). HR for single-agent chemotherapy was 0.70 (95% CI [0.50-0.96], P = 0.0288) and 0.48 for multi-agent (95% CI [0.38-0.62], P <0.0001). Overall survival was 86% in those that received chemotherapy vs 65% in those who did not (P <0.0001). CONCLUSIONS: In conclusion, patients with early-stage squamous cell cancer of the anus who are treated with combination chemoradiation continue to demonstrate better overall survival than those who undergo radiotherapy alone.

A Retrospective Analysis of Factors Affecting Palliative Care Consults in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Purpose This study was conducted to determine factors that influence palliative care (PC) consultation in patients receiving cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Patient and methods We queried our Electronic Medical Record EPIC for a list of patients who underwent cytoreductive surgery with HIPEC or hyperthermic intrathoracic chemotherapy (HITEC) in the hospital from April 2016-April 2019. Data was manually extracted and patients who did not meet our criteria were excluded. Patients were divided on the basis of palliative care consults and differences between the groups were analyzed. Odds ratios (OR) with p-value of 0.05 and confidence interval of (CI) 95% were calculated. Results We identified 55 patients of whom 34 met our inclusion criteria: 11 males and 23 females with an average age of 56 years at the time of diagnosis. Eight patients (23%) had PC, with six having commercial insurance, seven married, and six with more than one comorbid medical issue. Comorbidities >1 (OR: 0.12; CI: 0.02-0.76; p: 0.02) and age >40 (OR: 0.015; CI: 0.0007-0.3029; P: 0.006) were associated with a higher likelihood of PC. Gender, insurance type, and marital status did not have a significant association with PC. Mean age between PC consulted patients versus non-PC consulted patients was 58.5 vs. 55.9 and median age between the two groups was 60.5 vs. 60 which also showed a trend towards higher rates of PC in the older population. Conclusion Approximately one quarter of patients who underwent CRS with HIPEC had a concurrent PC consult. Though this is better than the national average of 11-16%, it continues to be a very small number. Efforts must be made to engage PC early in the course of treatment and recognize it as an integral part of cancer care. PC is not only an end-of-life service, in fact, studies have shown that early consultations lead to higher patient satisfaction, improved quality of life, and better communication.

Post-Operative Morbidity and Mortality Following Total Neoadjuvant Therapy Versus Conventional Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

BACKGROUND: Standard of care for locally advanced rectal cancer (LARC) (stage II/III) includes preoperative chemoradiation (CRT) followed by resection and adjuvant chemotherapy. Total neoadjuvant therapy (TNT) is a new treatment paradigm that delivers systemic therapy prior to CRT aimed at improving outcomes for high-risk patients. Here we analyzed the national cancer database (NCDB) comparing short-term post-operative outcomes between patients receiving TNT and CRT. METHODS: The NCDB was queried to identify patients with LARC between the 2004 and 2014 treated with TNT or CRT. Primary outcomes included post-operative 30-day mortality and readmissions between TNT and CRT which were analyzed via logistic regression. Secondary outcomes included post-operative length of stay (LOS) and OS which were compared with two-tailed t-test and Kaplan-Meier with log rank testing, respectively. RESULTS: A total of 9066 patients met inclusion criteria with a median age at diagnosis that was 57 years (IQR, 19-65); 62.3% were male and 87.8% white. Neoadjuvant therapy consisted of either standard CRT (97.2%) or TNT (2.8%). Patients treated at academic programs and those with N1 [p < 0.001, OR 2.34, 95%CI 1.71-3.19] or N2 [p < 0.001, OR 3.29, 95%CI 2.19-4.94] disease were associated with increased utilization of TNT. TNT was not significantly associated with either 30-day mortality (p = 1.0) or readmissions (p = 0.82). Further, there was no significant difference identified between CRT and TNT for hospital LOS or OS (p = 0.18). CONCLUSION: This large-scale analysis of patients with LARC demonstrates increased utilization of TNT in patients harboring node-positive disease. Further, TNT does not appear to increase 30-day post-operative mortality, readmissions, or hospital LOS.

An Internal Review of Rates of Palliative Medicine Referral for Patients With Advanced Pancreatic Cancer.

Background The American Society of Clinical Oncology recommends that patients with advanced cancer receive palliative care services in concurrence with active treatment. While the benefits of palliative care are clear, integration of palliative care can be challenging. We aim to review rates of palliative care consultation in patients with advanced pancreatic cancer at our institution, intending to improve these rates. Methods We retrospectively reviewed the electronic records of all patients with pancreatic cancer treated at Allegheny General Hospital diagnosed between 2009-2020. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Results Of the 171 patients reviewed, 121 completed all treatment and evaluation within our health network (Pittsburgh, United States). The median age was 63 years (IQR 40-91 years); 55 patients (45%) were male; the majority were white (107 patients, 88%). At the time of diagnosis, 28% of our patients had stage IV disease (34 patients), and 19.8% of patients who developed stage IV disease had palliative care referrals. Conclusions Palliative care is an integral part of usual care for advanced pancreatic cancer. Our analysis showed that palliative care is underutilized in our hospital. We aim to improve palliative care integration in our patients' care by adding a hard stop to electronic medical records to remind physicians to offer palliative care to our patients with pancreatic cancer and to arrange lecture series to emphasize the importance of palliative care in this setting.

Immunotherapy in gastroesophageal cancers: Current state and future directions.

While gastroesophageal (GE) cancers are one of the most common cancers worldwide, unfortunately, the mortality remains high. Commonly used treatment options include surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy, which improve survival only minimally; thus, affirming the dire need for exploring alternative strategies to improve patient outcomes. Immunotherapy, which has revolutionized the world of oncology, has somewhat lagged behind in GE malignancies. Tumor-associated microenvironment and regulatory T cells, alongside cell cycle checkpoints, have been proposed by various studies as the mediators of carcinogenesis in GE cancers. Thus, inhibition of each of these could serve as a possible target of treatment. While the approval of pembrolizumab has provided some hope, it is not enough to override the dismal prognosis that this disease confers. Herein, we discuss the prospects of immunotherapy in this variety of cancer.

Leukemoid reaction causing arterial thrombus in a patient with lung adenocarcinoma.

A leukemoid reaction is typically defined as white blood cell (WBC) count >50×109/L, predominantly neutrophil precursors, that are not due to tumour involvement in the bone marrow and not derived from clones. Leukemoid reactions associated with malignancy, known as paraneoplastic leukemoid reactions, are less common and are most notably seen with non-small cell lung cancer. A 64-year-old woman presented with right leg painful ulceration. On examination, she had multiple venous stasis ulcers more severe on the right, with no palpable pulses in her lower extremities. Her WBC count was 124×109/L and platelets were 517×109/L. Arterial dopplers showed limb-threatening arterial insufficiency which prompted right femoral endarterectomy. Few months earlier she was diagnosed with metastatic lung adenocarcinoma to the bone and she had leukemoid reaction with WBC 43.920× 109/L with 90% neutrophils. Repeat imaging showed progression of her malignancy and she passed shortly after. Inflammation is a key element of carcinogenesis and cancer progression. Among the different tumours, lung cancer is a non-haematologic malignancy that is most closely associated with leucocytosis. Some studies have found that leucocytosis was significantly associated with metastasis and shorter survival irrespective of other factors such as age or sex. The mechanism remains unclear however elevated levels of granulocyte colony-stimulating factor (CSF), granulocyte macrophage-CSF and interleukin 6 have been linked to this phenomena. The degree of leucocytosis seen in our patient is suggestive of CSF production leading to a paraneoplastic leukemoid reaction.

First Reported Case of Localized Extra-pulmonary Small Cell Carcinoma (EPSC) of the Esophagus Treated With Triple Therapy.

BACKGROUND/AIM: Early stage extra-pulmonary small cell carcinoma (EPSC) of the esophagus is very rare and is usually treated with chemo-radiation or surgical resection. CASE REPORT: A case of early stage small cell carcinoma of the esophagus that was treated with all three current modalities of chemotherapy, radiation, and surgery. To our best knowledge this is the first case treated with triple therapy. The patient is a 64-year-old male with increasing gastroesophageal reflux disease (GERD) symptoms. EGD biopsy of the mass showed small cell carcinoma. Metastatic work up was negative. Patient was treated with 6 cycles of a platinum-based agents and Etoposide along with radiation. Patient underwent distal esophagectomy. Patient is alive without evidence of recurrent disease at 20 months follow up. CONCLUSION: Currently there are no definite treatment recommendations, but we present a possible future option with good outcomes in patients who can tolerate triple therapy.

A Rare Case of Locally Advanced Primary Small Cell Neuroendocrine Carcinoma of the Adrenal Gland.

BACKGROUND/AIM: Primary small cell neuroendocrine carcinoma (SCNEC) of the adrenal gland is extremely rare with limited reports in the literature. There remain no definitive treatment guidelines, largely due to the rarity of the malignancy. CASE REPORT: We present the case of a 62-year-old Caucasian male who presented with low back pain and was found to have a large retroperitoneal mass arising from the left adrenal gland, measuring 18.3 × 12.2 centimeters (cm). Biopsy was consistent with small cell carcinoma/high grade neuroendocrine carcinoma. Staging workup including CT chest and bone scan was negative. The patient was treated with chemotherapy, radiation therapy, and surgery; complete pathological response of the left adrenal tumor was achieved. Surveillance imaging every three months continued to show no evidence of recurrent disease. CONCLUSION: Primary SCNEC of the adrenal gland is rare and lacks standard treatment guidelines. Our case represents a possible treatment approach that may provide better clinical outcomes, however, further investigations are necessary to help define ideal treatment guidelines.

Molecular Profiling of Advanced Malignancies: A Community Oncology Network Experience and Review of Literature.

Background: Many genomic alterations have been identified that are critical to the malignant phenotype. Some of these, termed "driver mutations," are critical for tumor proliferation and progression. The landscape of targeted therapy has expanded as well. Next-generation sequencing (NGS) of tumors reveals cancer-related genomic alterations and provides therapeutic recommendations for specific targeted therapy. We analyzed our experience with FoundationOne, a validated NGS genomic profiling test, in a community oncology network. Methods: NGS results from May 2014 to September 2016 from a community oncology network in Western Pennsylvania were analyzed. Medical records were reviewed for primary site, stage, biopsy site, time of testing, prior treatment, FDA-approved therapy in patient's and other tumor types and potential clinical trials based upon mutations detected. Two co-primary endpoints for this study were to determine the percentage of patients having mutations with a FDA-approved targeted agent and the percentage of patients in whom a treatment decision was made based on these NGS results. Results: One Fifty-Seven NGS results were available for analysis. 82% patients had a mutation with a FDA-approved targeted agent available while 18% patients had no FDA-approved targeted agent for the mutation detected. Clinical trials were available for 93% cases. The NGS results were utilized in treatment decisions in 18% patients (n = 28) with, 7% (n = 11) initiating a targeted agent, 6% (n = 9) were on an appropriate targeted agent prior to testing and 5% (n = 8) being unable to start a targeted agent because of insurance denial, clinical deterioration or patient preference. 38% cases were tested early in the disease course (at diagnosis, during or shortly after first-line treatment) and 62% at progression. Conclusions: NGS is a valuable tool to identify molecular targets for personalizing cancer care. From our experience, the actual number of patients starting a targeted agent based on NGS results is low but it provides substantial information in terms of providing additional treatment options, identifying resistance conferring mutations and facilitating clinical trial enrollment. Optimal time of testing, early or late in disease course, financial implications of testing and using targeted therapy and survival benefit of targeted therapy need further studies.

Impact of affordable care act on the treatment and outcomes for stage-IV colorectal cancer.

BACKGROUND: Patients with advanced cancers are among the most vulnerable group of patients. We sought to analyze the impact of Affordable Care Act (ACA) on the interaction of socioeconomic factors with treatment and survival in patients with metastatic colorectal cancers. METHODS: National Cancer Database (NCDB) was queried for patients with Stage-IV colon(CCa) and rectal cancers(R-Ca) diagnosed 2004-2015 and excluded those who did not receive any therapies within 6 months of diagnosis. Enrollment-rates were calculated as receipt of primary therapy as the incident-event (numerator) over time-to-initiation of therapy (denominator) and used to calculate incident-rate ratios that was analyzed using Poisson regression analysis- reported as enrollment-rate ratios (ER, <1 indicating lower enrollment rate). Multivariate Cox-proportional hazard model was performed for survival analysis and reported as calculate Hazard Ratios (HR). RESULTS: For CCa, enrollment to primary therapies was significantly associated (p-value < 0.05) with gender, race, insurance status, educational status and treatment facility. The HR for non-Hispanic Blacks (NHB) vs. Whites (NHW) improved from 1.1(1.03-1.11),p-value<0.005 to no-significant difference post-ACA. For R-Ca, the enrollment rates were favorable for NHB vs. NHW and ER improved from 1.15(1.0-1.32),p-value = 0.054) to 1.29(1.06-1.58),p-value = 0.013 post-ACA. Despite this, the HR for mortality were unfavorable - 1.19(1.06-1.33),p-value = 0.003 that persisted through the post-ACA period. The HR was favorable for the insured group in both cancer groups (0.84 for R-Ca,0.86 for CCa) and for high-income vs. low-income group-0.90(0.87-0.94),p-value < 0.005 in CCa. CONCLUSION: The ACA appears to have had a positive impact overall but further research and ongoing interventions are warranted to mitigate disparities in this population.

Microsatellite Instability (MSI) as an Independent Predictor of Pathologic Complete Response (PCR) in Locally Advanced Rectal Cancer: A National Cancer Database (NCDB) Analysis.

OBJECTIVE: The relationship between microsatellite instability (MSI) and response to neoadjuvant chemoradiation in rectal cancer is not well understood. BACKGROUND: We utilized the National Cancer Database (NCDB) to investigate the association between MSI and pathologic complete response (pCR) in this patient population. METHODS: We analyzed 5086 patients between 2010 and 2015 with locally advanced rectal cancer who were tested for MSI and treated definitively with chemoradiation followed by surgery. Primary comparison groups were between 4450 MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression analysis was conducted to identify demographic, therapeutic, and clinical characteristics predictive of pCR. Cox proportional-hazard ratios were used for survival. RESULTS: All patients were treated with definitive chemoradiation (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were associated with earlier year of diagnosis and higher-grade tumors (P < 0.05).The overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated with a reduced pCR rate (odds ratio 0.65, 95% confidence interval 0.43-0.96) with multivariable analysis. The 5-year survival for patients with pCR was 93% compared with 73% without it (<0.001). CONCLUSION: Microsatellite instability was independently associated with a reduction in pCR for locally advanced rectal cancer after neoadjuvant chemoradiation in this NCDB-based analysis.