Nodal staging with MRI after neoadjuvant chemo-radiotherapy for locally advanced rectal cancer: a fast and reliable method.

OBJECTIVES: In patients with locally advanced rectal carcinoma (LARC), negative nodal status after neoadjuvant chemoradiotherapy (nCRT) may allow for rectum-sparing protocols rather than total mesorectal excision; however, current MRI criteria for nodal staging have suboptimal accuracy. The aim of this study was to compare the diagnostic accuracy of different MRI dimensional criteria for nodal staging after nCRT in patients with LARC. MATERIALS AND METHODS: Patients who underwent MRI after nCRT for LARC followed by surgery were retrospectively included and divided into a training and a validation cohort of 100 and 39 patients, respectively. Short-, long-, and cranial-caudal axes and volume of the largest mesorectal node and nodal status based on European Society of Gastrointestinal Radiology consensus guidelines (i.e., ESGAR method) were assessed by two radiologists independently. Inter-reader agreement was assessed in the training cohort. Histopathology was the reference standard. ROC curves and the best cut-off were calculated, and accuracies compared with the McNemar test. RESULTS: The study population included 139 patients (median age 62 years [IQR 55-72], 94 men). Inter-reader agreement was high for long axis (κ = 0.81), volume (κ = 0.85), and ESGAR method (κ = 0.88) and low for short axis (κ = 0.11). Accuracy was similar (p > 0.05) for long axis, volume, and ESGAR method both in the training (71%, 74%, and 65%, respectively) and in the validation (83%, 78%, and 75%, respectively) cohorts. CONCLUSION: Accuracy of the measurement of long axis and volume of the largest lymph node is not inferior to the ESGAR method for nodal staging after nCRT in LARC. CLINICAL RELEVANCE STATEMENT: In MRI restaging of rectal cancer, measurement of the long axis or volume of largest mesorectal lymph node after preoperative chemoradiotherapy is a faster and reliable alternative to ESGAR criteria for nodal staging. KEY POINTS: • Current MRI criteria for nodal staging in locally advanced rectal cancer after chemo-radiotherapy have suboptimal accuracy and are time-consuming. • Measurement of long axis or volume of the largest mesorectal lymph node on MRI showed good accuracy for assessment of loco-regional nodal status in locally advanced rectal cancer. • MRI measurement of the long axis and volume of largest mesorectal lymph node after chemo-radiotherapy could be a faster and reliable alternative to ESGAR criteria for nodal staging.

Diagnostic accuracy of state-of-the-art rectal MRI sequences for the diagnosis of extramural vascular invasion in locally advanced rectal cancer after preoperative chemoradiotherapy: dos or maybes?

OBJECTIVES: The aim of this study was to determine the accuracy of three state-of-the-art MRI sequences for the detection of extramural venous invasion (EMVI) in locally advanced rectal cancer (LARC) patients after preoperative chemoradiotherapy (pCRT). METHODS: This retrospective study included 103 patients (median age 66 years old [43-84]) surgically treated with pCRT for LARC and submitted to preoperative contrast-enhanced pelvic MRI after pCRT. T2-weighted, DWI, and contrast-enhanced sequences were evaluated by two radiologists with expertise in abdominal imaging, blinded to clinical and histopathological data. Patients were scored according to the probability of EMVI presence on each sequence using a grading score ranging from 0 (no evidence of EMVI) to 4 (strong evidence of EMVI). Results from 0 to 2 were ranked as EMVI negative and from 3 to 4 as EMVI positive. ROC curves were drawn for each technique, using histopathological results as reference standard. RESULTS: T2-weighted, DWI, and contrast-enhanced sequences demonstrated an area under the ROC curve (AUC) respectively of 0.610 (95% CI: 0.509-0.704), 0.729 (95% CI: 0.633-0.812), and 0.624 (95% CI: 0.523-0.718). The AUC of DWI sequence was significantly higher than that of T2-weighted (p = 0.0494) and contrast-enhanced (p = 0.0315) sequences. CONCLUSIONS: DWI is more accurate than T2-weighted and contrast-enhanced sequences for the identification of EMVI following pCRT in LARC patients. CLINICAL RELEVANCE STATEMENT: MRI protocol for restaging locally advanced rectal cancer after preoperative chemoradiotherapy should routinely include DWI due to its higher accuracy for the diagnosis of extramural venous invasion compared to high-resolution T2-weighted and contrast-enhanced T1-weighted sequences. KEY POINTS: • MRI has a moderately high accuracy for the diagnosis of extramural venous invasion in locally advanced rectal cancer after preoperative chemoradiotherapy. • DWI is more accurate than T2-weighted and contrast-enhanced T1-weighted sequences in the detection of extramural venous invasion after preoperative chemoradiotherapy of locally advanced rectal cancer. • DWI should be routinely included in the MRI protocol for restaging locally advanced rectal cancer after preoperative chemoradiotherapy.

FOXO transcriptional activity is associated with response to chemoradiation in EAC.

In this study we aimed to investigate signaling pathways that drive therapy resistance in esophageal adenocarcinoma (EAC). Paraffin-embedded material was analyzed in two patient cohorts: (i) 236 EAC patients with a primary tumor biopsy and corresponding post neoadjuvant chemoradiotherapy (nCRT) resection; (ii) 66 EAC patients with resection and corresponding recurrence. Activity of six key cancer-related signaling pathways was inferred using the Bayesian inference method. When assessing pre- and post-nCRT samples, lower FOXO transcriptional activity was observed in poor nCRT responders compared to good nCRT responders (p = 0.0017). This poor responder profile was preserved in recurrences compared to matched resections (p = 0.0007). PI3K pathway activity, inversely linked with FOXO activity, was higher in CRT poor responder cell lines compared to CRT good responders. Poor CRT responder cell lines could be sensitized to CRT using PI3K inhibitors. To conclude, by using a novel method to measure signaling pathway activity on clinically available material, we identified an association of low FOXO transcriptional activity with poor response to nCRT. Targeting this pathway sensitized cells for nCRT, underlining its feasibility to select appropriate targeted therapies.

Pretreatment CT and PET radiomics predicting rectal cancer patients in response to neoadjuvant chemoradiotherapy.

BACKGROUND: The purpose of this study was to characterize pre-treatment non-contrast computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography (PET) based radiomics signatures predictive of pathological response and clinical outcomes in rectal cancer patients treated with neoadjuvant chemoradiotherapy (NACR T). MATERIALS AND METHODS: An exploratory analysis was performed using pre-treatment non-contrast CT and PET imaging dataset. The association of tumor regression grade (TRG) and neoadjuvant rectal (NAR) score with pre-treatment CT and PET features was assessed using machine learning algorithms. Three separate predictive models were built for composite features from CT + PET. RESULTS: The patterns of pathological response were TRG 0 (n = 13; 19.7%), 1 (n = 34; 51.5%), 2 (n = 16; 24.2%), and 3 (n = 3; 4.5%). There were 20 (30.3%) patients with low, 22 (33.3%) with intermediate and 24 (36.4%) with high NAR scores. Three separate predictive models were built for composite features from CT + PET and analyzed separately for clinical endpoints. Composite features with α = 0.2 resulted in the best predictive power using logistic regression. For pathological response prediction, the signature resulted in 88.1% accuracy in predicting TRG 0 vs. TRG 1-3; 91% accuracy in predicting TRG 0-1 vs. TRG 2-3. For the surrogate of DFS and OS, it resulted in 67.7% accuracy in predicting low vs. intermediate vs. high NAR scores. CONCLUSION: The pre-treatment composite radiomics signatures were highly predictive of pathological response in rectal cancer treated with NACR T. A larger cohort is warranted for further validation.

Indistinguishable T2/T3-N0 rectal cancer on rectal magnetic resonance imaging: comparison of surgery-first and neoadjuvant chemoradiation therapy-first strategies.

PURPOSE: We compared the treatment outcome between surgery-first and neoadjuvant chemoradiation therapy (nCRT)-first strategies in patients with indistinguishable T2/T3-N0 rectal cancer on rectal magnetic resonance imaging (MRI). METHODS: Our institutional review board approved this retrospective study, and informed consent was waived. Among 1910 patients who underwent rectal MRI between 2008 and 2012, 79 patients (mean age, 59.4 years, 49 men and 30 women) who had indistinguishable T2/T3-N0 rectal cancer on rectal MRI were included. Local recurrence-free survival (LRFS), recurrence-free survival (RFS), overall survival (OS), and disease-specific survival (DSS) were compared between the two groups. Treatment-related complications were evaluated. RESULTS: Among 79 patients, 51 were treated by surgery first and 28 were treated by nCRT first. In comparison of survival of the surgery- and nCRT-first groups at 5 years, the LRFS rate was 95.6 and 96.3%, RFS rate was 91.0 and 92.4%, OS rate was 93.7 and 92.6%, and DSS rate was 98.0 and 92.6%, respectively. LRFS, RFS, OS, and DSS showed no significant difference between the two groups (p = 0.862, 0.677, 0.953, and 0.479). The complication rate was not significantly different between the groups (20.0% for surgery-first group vs. 10.7% for nCRT-first group, p = 0.357). CONCLUSION: Treatment outcomes were not significantly different between surgery-first and nCRT-first strategies for indistinguishable T2/T3-N0 rectal cancer on rectal MRI.

ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).

BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.

Pathologic response grade after long-course neoadjuvant chemoradiation does not influence morbidity in locally advanced mid-low rectal cancer resected by laparoscopy.

PURPOSE: Patients with locally advanced rectal cancer and pathologic complete response to neoadjuvant chemoradiation therapy have lower rates of recurrence compared to those who do not. However, the influences of the pathologic response on surgical complications and survival remain unclear. This study aimed to investigate the influence of neoadjuvant therapy for rectal cancer on postoperative morbidity and long-term survival. METHODS: This was a comparative study of consecutive patients who underwent laparoscopic total mesorectal excision for rectal cancer in two European tertiary hospitals between 2004 and 2014. Patients with and without pathologic complete responses were compared in terms of postoperative morbidity, mortality, and survival. RESULTS: Fifty patients with complete response (ypT0N0) were compared with 141 patients who exhibited non-complete response. No group differences were observed in the postoperative mortality or morbidity rates. The median follow-up time was 57 months (range 1-121). Over this period, 11 (5.8 %) patients, all of whom were in the non-complete response group, exhibited local recurrence. The 5-year overall survival and disease-free survival were significantly better in the complete response group, 92.5 vs. 75.3 % (p = 0.004) and 89 vs. 73.4 % (p = 0.002), respectively. CONCLUSIONS: Postoperative complication rate after laparoscopic total mesorectal excision is not associated with the pathologic response grade to neoadjuvant chemoradiation therapy.

Endoscopic and Imaging Predictors of Complete Pathologic Response After Chemoradiation for Esophageal Cancer.

PURPOSE OF REVIEW: Locally advanced esophageal cancer is frequently treated preoperatively with chemotherapy and radiation. The degree of response to this preoperative therapy varies in different patients, and a complete pathological response (pCR) has important implications in the management and prognosis of these patients. This is a review of the different modalities currently available to detect pCR and the clinical context of their use. RECENT FINDINGS: While research is still ongoing, no single technique has emerged as the modality of choice to reliably predict pCR in all patients. Studies investigating the sensitivity, specificity, and accuracy of these modalities have had promising results, but no single modality has been firmly validated as the modality if choice. The emergence of functional imaging techniques and the use of biomarkers are newer developments which need further evaluation before adoption in routine clinical practice. While no single technique reliably predicts pCR, a combination of imaging and diagnostic modalities (endoscopic appearance, biopsy, EUS, and PET/CT) may provide a better diagnostic yield rather than any of these modalities taken alone.

Effect of Neoadjuvant Chemoradiation Therapy on Proteasome Pool in Rectal Cancer.

In untreated rectal cancer patients, the chymotrypsin-like activity of proteasomes in tumor tissue was 3-fold higher than that in conventionally normal tissue, which is explained by up-regulation of expression of immunoproteasomes and total pool of proteasomes. After neoadjuvant chemoradiation therapy, expressions of the total pool of proteasomes and immunoproteasomes in the tumor as well as the relative ratios of these indices to those in conventionally normal tissue were smaller by 1.4-3.3 times in comparison with the untreated patients. These changes were paralleled with pronounced (4.5-fold) down-regulation of proteasome activity in the tumor and a 3.7-fold decrease of activity ratio for the proteasomes in tumor and in conventionally normal tissue. The number of immunoproteasome subunits and the chymotrypsin-like activity of proteasomes can be viewed as potential markers to prognosticate effectiveness of neoadjuvant chemoradiation therapy in rectal cancer patients.

Diagnostic performance of MRI for prediction of candidates for local excision of rectal cancer (ypT0-1N0) after neoadjuvant chemoradiation therapy.

PURPOSE: To evaluate the diagnostic performance of rectal MRI in predicting candidates for local excision (LE; ypT0-1N0) after neoadjuvant chemoradiation therapy (CRT) in patients with rectal cancer. MATERIALS AND METHODS: The institutional review board approved our retrospective study and waived informed consent. Inclusion criteria were as follows: patients with pathologically confirmed mid to lower rectal cancer (cT3NxM0 before neoadjuvant CRT) who underwent neoadjuvant CRT and had MRI performed at 3T before and after neoadjuvant CRT. A total of 168 patients met the study criteria between 2011 and 2012. Two observers independently assessed tumor and nodal stages on MR images obtained after neoadjuvant CRT. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for identifying a candidate for LE (ypT0-1N0) were calculated. Interobserver agreement was assessed with kappa value. Predictive factors for ypT0-1N0 were evaluated by logistic regression models. RESULTS: MRI had relatively high accuracy, specificity, and NPV (85.9%, 93.8%, and 88.9% for observer 1 and 85.3%, 96.1%, and 86.6% for observer 2), moderate PPV (71.4% and 76.2%), and relatively low sensitivity (57.1% and 45.7%) for predicting ypT0-1N0. The interobserver agreement was fair (kappa value = 0.593). Carcinoembryonic antigen levels after neoadjuvant CRT and the maximal extramural depth of tumor spread were significant predictors of ypT0-1N0 (P = 0.037 and 0.017, respectively). CONCLUSION: MRI after neoadjuvant CRT can predict a candidate for LE (ypT0-1N0) after neoadjuvant CRT with moderate PPV and relatively high NPV. J. Magn. Reson. Imaging 2016;44:471-477.

Clinical relevance of morphologic MRI criteria for the assessment of lymph nodes in patients with rectal cancer.

AIM: The aim of this study is the evaluation of lymph node staging by magnetic resonance imaging (MRI) within clinical routine in patients with rectal cancer. METHOD: Routine MRI reports (3 T) of 65 consecutive patients with rectal cancer were retrospectively categorized in lymph node tumor positive or negative (mriN+; mriN0) and compared to the final histopathological results (pN+; pN0). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy were calculated. The original MRI readings were then reanalyzed in order to identify the longest short-axis lymph node diameter for each patient. A receiver operating characteristic (ROC) curve was used to calculate a possible cutoff value for the short-axis lymph node diameter. RESULTS: Overall sensitivity was 94 %, specificity 13 %, NPV 86 %, PPV 28 %, and accuracy 34 %. The best accuracy could be calculated for a short-diameter cutoff of ≤5 mm (83 %); pN+ and pN0 groups were then significantly different (p < 0.0001). CONCLUSION: In clinical routine, lymph node assessment in patients with rectal cancer through MRI tends to overstage malignant lymphadenopathy. A ≤5-mm cutoff value for the short-axis lymph node diameter of benign nodes is able to improve the accuracy and has potential to lower the risk of overstaging.

Covered self-expandable metal stent deployment promises safe neoadjuvant chemoradiation therapy in patients with borderline resectable pancreatic head cancer.

BACKGROUND: Patients with borderline resectable pancreatic head cancer (BRPHC) have been treated with neoadjuvant chemoradiation therapy (NACRT) using metallic stents. The aim of the present study was to evaluate the efficacy and complications of covered self-expanding metallic stents (CSEMS) during the NACRT and surgical period. PATIENTS AND METHODS: We reviewed the outcomes of patients with BRPHC, then divided them chronologically into three groups as follows. Group A: upfront surgery with plastic stent (PS) deployment; group B: PS deployment plus neoadjuvant chemotherapy (NAC) and/or NACRT; group C: CSEMS deployment plus NAC/NACRT. Patients were categorized as borderline resectable based on National Comprehensive Cancer Network Guidelines, 2010. Days to reintervention (DR), reintervention rate, and the rate of R0 and complications were studied. Safe margin-negative resection (R0) surgery was defined as R0 surgery without reintervention during the NACRT period and no postoperative complications. RESULTS: DR were as follows. Groups A, B and C were 32, 55 and 97 days, respectively (P < 0.05). R0 surgery obtained in groups A, B and C was 53% (9/17), 100% (17/17) and 93% (14/15), respectively. CSEMS did not interfere with surgery. Safe R0 surgery obtained in groups B and C was 11% (2/19) and 67% (10/15), respectively (P < 0.05). Multivariate analysis showed that the odds ratio for safe R0 surgery was 16.210 (95% CI 2.457-106.962, P = 0.003) for CSEMS placement. CONCLUSION: CSEMS should be considered to relieve symptomatic biliary obstruction in patients with BRPHC receiving NACRT in view of the high attainability rate of safe R0 surgery compared to that with PS deployment.

Magnetic resonance imaging for assessment of rectal cancer nodes after chemoradiotherapy: A single center experience.

BACKGROUND: Accurate nodal restaging is becoming clinically more important in patients with locally advanced rectal cancer (LARC) with the emergence of organ-preserving treatment after a good response to neoadjuvant chemoradiotherapy (nCRT). PURPOSE: To evaluate the accuracy of MRI in identifying negative N status (ypN0 patients) in LARC after nCRT. MATERIAL AND METHODS: 191 patients with LARC underwent MRI before and 6-8 weeks after nCRT and subsequent total mesorectal excision. Short-axis diameter of mesorectal lymph nodes was evaluated on the high resolution T2-weighted images to compare MRI restaging with histopathology.. RESULTS: 146 and 45 patients had a negative N status (ypN0) and positive N status (ypN + ), respectively. On restaging MRI, the 70 % reduction in size of the largest node was associated with an area under the curve (AUC) of 0.818 to predict ypN0 stage, with a sensitivity of 93.3 % and a negative predictive value (NPV) of 95.4 %. No nodes were observed in 38 pts (37 pts ypN0 and 1 patient ypN + ), with sensitivity and NPV of nodes disappearance for ypN0 stage of 93.3 % and 92.5 % respectively. A 2.2 mm cut-off in short-axis diameter was associated with an AUC of 0.83 for the prediction of ypN0 nodal stage, with sensitivity and NPV of 79,5% and 91.1 % respectively. CONCLUSION: A reduction in size of 70 % of the largest limph-node on MRI at rectal cancer restaging has high sensitivity and NPV for prediction of ypN0 stage after nCRT. The high NPV of node disappearance and of a ≤ 2.2 mm short-axis diameter is confirmed.

Predicting Neoadjuvant Treatment Response in Rectal Cancer Using Machine Learning: Evaluation of MRI-Based Radiomic and Clinical Models.

BACKGROUND: Radiomics is an approach to medical imaging that quantifies the features normally translated into visual display. While both radiomic and clinical markers have shown promise in predicting response to neoadjuvant chemoradiation therapy (nCRT) for rectal cancer, the interrelationship is not yet clear. METHODS: A retrospective, single-institution study of patients treated with nCRT for locally advanced rectal cancer was performed. Clinical and radiomic features were extracted from electronic medical record and pre-treatment magnetic resonance imaging, respectively. Machine learning models were created and assessed for complete response and positive treatment effect using the area under the receiver operating curves. RESULTS: Of 131 rectal cancer patients evaluated, 68 (51.9%) were identified to have a positive treatment effect and 35 (26.7%) had a complete response. On univariate analysis, clinical T-stage (OR 0.46, p = 0.02), lymphovascular/perineural invasion (OR 0.11, p = 0.03), and statin use (OR 2.45, p = 0.049) were associated with a complete response. Clinical T-stage (OR 0.37, p = 0.01), lymphovascular/perineural invasion (OR 0.16, p = 0.001), and abnormal carcinoembryonic antigen level (OR 0.28, p = 0.002) were significantly associated with a positive treatment effect. The clinical model was the strongest individual predictor of both positive treatment effect (AUC = 0.64) and complete response (AUC = 0.69). The predictive ability of a positive treatment effect increased by adding tumor and mesorectal radiomic features to the clinical model (AUC = 0.73). CONCLUSIONS: The use of a combined model with both clinical and radiomic features resulted in the strongest predictive capability. With the eventual goal of tailoring treatment to the individual, both clinical and radiologic markers offer insight into identifying patients likely to respond favorably to nCRT.

The "Watch and Wait" Method After Chemoradiotherapy for Rectal Cancer Requiring Abdominoperineal Resection.

The present study examined the therapeutic effects of preoperative neoadjuvant chemoradiation therapy (NACRT) and predictive factors for complete clinical remission, compared the prognosis and costs of abdominoperineal resection (APR) and the "watch and wait" method (WW), and evaluated the usefulness of WW. In our department, patients with stage II-III lower rectal cancer requiring APR receive NACRT. NACRT was performed as a preoperative treatment (52 Gy + S-1: 80-120 mg/day × 25 days). Eight weeks after the completion of NACRT, rectal examination, endoscopic, computed tomography, and magnetic resonance imaging findings were evaluated to assess its therapeutic effects. APR was indicated for patients in whom endoscopic findings suggested a residual tumor in which a deep ulcer or marginal swelling remained or lymph node metastasis. However, WW was selected for patients who refused APR after informed consent was obtained. In the APR and WW groups, 5- and 20-year treatment costs after CRT were calculated using the Medical Fee Points of Japan in 2020. No significant differences were observed in 3-year disease-free survival rates for either parameter between the two groups. Regarding expenses, treatment costs were lower in the WW group than in the APR group. Organ preservation using active surveillance with CRT for rectal cancer requiring APR is feasible with the achievement of endoluminal complete remission.

Prognostic impact of lymph node spreading pattern in N2 NSCLC patients.

BACKGROUND: One-third of non-small cell lung cancer (NSCLC) patients are diagnosed with locally advanced disease. Long-term survival in stage IIIA/B-N2 remains poor; this may also be due to lymph node spreading pattern. Therefore, we compared the overall survival of stage IIIA/B-N2 patients with superior mediastinal lymph nodes (SML) with infracarinal- or inferior mediastinal lymph nodes (IML) and with multilevel disease (MLD). RESEARCH DESIGN AND METHODS: One-, three-and five-year survival rates were measured. Kaplan-Meier curves and Cox proportional hazards model assessed survival and were used to identify prognostic factors. RESULTS: We reviewed data of stage IIIA/B-N2 patients (n = 129) who underwent surgery for NSCLC between 2012 and 2020. Patients with SML (n = 62) were compared to ILM (n = 37) and MLD (n = 30). SML patients showed significantly better one- (SML: 95.2% vs. IML: 78.6% vs. MLD: 69.4%, p = 0.03), three- (78.8% vs. 27.7 vs. 13.3%; p = <0.001) and five-year (61.1% vs. 17.1 vs. 3%; p < 0.001) survival rates, than IML and MLD patients. Kaplan-Meier curves showed prolonged overall survival for SML patients (log-rank SML, ILM, MLD p < 0.0001). CONCLUSIONS: This study showed significantly better long-term survival of SML patients than IML and MLD patients. The long-term survival of ILM and MLD patients was equally poor.

Prognostic Impact of Pretreatment Serum CYFRA Status in 1047 Patients with Esophageal Squamous Cell Carcinoma Who Underwent Radical Resection: A Japan Esophageal Society Promotion Research.

PURPOSE: The prognostic significance of pretreatment serum C-terminus of cytokeratin 19 (CYFRA21-1, CYFRA) status was evaluated in the patients with surgically treated esophageal squamous cell carcinoma. METHODS: A total of 1047 patients with surgically treated esophageal cancer were enrolled in a multi-institutional study promoted by the Japanese Esophageal Society. This study included an up-front surgery group (n = 412), a neoadjuvant chemotherapy (NAC) group (n = 486), and a neoadjuvant chemoradiation/radiation therapy (NACRT/RT) group (n = 149). The pretreatment CYFRA status was analyzed to assess prognostic significance using multivariate analysis according to treatment modalities. RESULTS: The CYFRA-positive group was significantly associated with deep tumor. Univariate analysis showed that the overall survival of the CYFRA-positive group was significantly worse than that of the CYFRA-negative group, but the difference was not significant in the multivariate analysis. CYFRA was an independent risk factor for poor prognosis just in the NACRT/RT group. CONCLUSIONS: The CYFRA-positive group was associated with deep tumor and poor survival. Pretreatment CYFRA was not an independent risk factor for poor prognosis in the up-front surgery group or NAC group. It was an independent risk factor for poor prognosis just in the NACRT/RT group.

Impact of pathological complete response following neoadjuvant chemotherapy (gemcitabine, nab-paclitaxel, S-1) and radiation for borderline resectable pancreatic cancer: a case report and review of literature.

BACKGROUND: Pancreatic cancer (PC) is a highly lethal malignancy, even if surgical resection is possible (median survival: < 30 months). The prognosis of borderline resectable pancreatic cancer (BR-PC) is even worse. There is no clear consensus on the optimal treatment strategy, including pre/postoperative therapy, for BR-PC. We report a patient with BR-PC who achieved clinical partial response with neoadjuvant chemoradiation therapy (NACRT) and underwent curative resection, resulting in pathological complete response (pCR). CASE PRESENTATION: A 71-year-old man with jaundice and liver dysfunction was referred to our department because of a 48-mm hypo-vascular mass in the pancreatic head with obstruction of the pancreatic and bile ducts and infiltration of superior mesenteric vein and portal vein. The lesion was identified as atypical cells which suggested adenocarcinoma by biopsy, and he was administered NACRT: gemcitabine and nab-paclitaxel, following S-1 and intensity modulated radiation therapy. After reduction in the tumor size (clinical partial response), pancreaticoduodenectomy was performed, and pCR achieved. Postoperative adjuvant chemotherapy with S-1 was initially administered and the patient is currently alive with no recurrence as of 2 years after surgery. CONCLUSIONS: NACRT is a potentially useful treatment for BR-PC that may lead to pCR and help improve prognosis.

Histopathological and Haemogram Features Correlate with Prognosis in Rectal Cancer Patients Receiving Neoadjuvant Chemoradiation without Pathological Complete Response.

BACKGROUND: Neoadjuvant chemoradiation therapy (NCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC); approximately 80% of patients do not achieve complete response. Identifying prognostic factors predictive of survival in these patients to guide further management is needed. The intratumoural lymphocytic response (ILR), peritumoural lymphocytic reaction (PLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PtLR) are correlated with the tumour microenvironment and cancer-related systemic inflammation. This study aimed to explore the ability of the ILR, PLR, NLR, and PtLR to predict survival in LARC patients without a complete response to NCRT. METHODS: Sixty-nine patients who underwent NCRT and surgery were retrospectively reviewed. The ILR and PLR were assessed in surgical specimens, and the NLR and PtLR were calculated using pre- and post-NCRT blood count data. The Kaplan-Meier method and Cox regression analyses were performed for survival analysis. RESULTS: A high PLR and high post-NCRT NLR and PtLR were significantly associated with better prognosis. Lymphovascular invasion (LVI), post-NCRT neutrophil count, and lymphocyte count were significant predictors of overall survival. LVI and the PLR were independent predictors of disease-free survival. CONCLUSIONS: NCRT-induced local and systemic immune responses are favourable prognostic predictors in LARC patients without complete response to NCRT.

A Rare Case of Metastatic Esophageal Adenocarcinoma Presenting as an Isolated Cerebellar Lesion 5 Years After Treatment.

Isolated brain metastasis (IBM) as a recurrence of primary esophageal adenocarcinoma (AC) has rarely been reported in the literature and typically manifests within a short period of time after diagnosing the primary lesion. We present here an unusual case of an IBM presenting nearly 5 years after neoadjuvant chemoradiation therapy and surgical resection of a primary distal esophageal tumor with no interval evidence of recurrence. A 53-year-old man presented to our gastroenterology clinic with progressive dysphagia and weight loss. On upper endoscopy, the patient was found to have a large obstructing distal esophageal mass with biopsies reported as moderately differentiated AC. Subsequent computed tomography (CT) chest/abdomen/pelvis (C/A/P) and magnetic resource imaging (MRI) brain were negative for any distant metastases. The patient received preoperative chemotherapy and radiation therapy, followed by distal esophagectomy with findings of stage IIIB disease. He did well after surgery and was monitored closely by his oncologist with no evidence of recurrence on interval imaging or follow-up endoscopy. Several years after his diagnosis, however, the patient developed new neurologic symptoms, and an MRI brain revealed a solitary cerebellar lesion with surrounding edema concerning for metastatic disease. Positron emission tomography and CT C/A/P were negative for any other new lesions. The tumor was resected, and pathology was confirmed as metastatic AC of esophageal origin. To our knowledge, this is the first case of recurrent esophageal AC presenting as an isolated cerebellar lesion 5 years after treatment of the primary tumor.