Neoadjuvant Chemoradiation For Esophageal Cancer Research Articles

ASO Author Reflections: Significance of Skeletal Muscle Loss After Neoadjuvant Chemoradiation for Esophageal Cancer.

ASO Author Reflections: Significance of Skeletal Muscle Loss After Neoadjuvant Chemoradiation for Esophageal Cancer.

Factors affecting timing of surgery following neoadjuvant chemoradiation for esophageal cancer

BackgroundNeoadjuvant chemoradiation with esophagectomy is standard management for locally advanced esophageal cancer. Studies have shown that surgical timing following chemoradiation is important for minimizing postoperative complications, however in practice timing is often variable and delayed. Although postoperative impact of surgical timing has been studied, less is known about factors associated with delays. Materials and methodsA retrospective review was performed for 96 patients with esophageal cancer who underwent chemoradiation then esophagectomy between 2018 and 2020 at a single institution. Univariable and stepwise multivariable analyses were used to assess association between social (demographics, insurance) and clinical variables (pre-operative weight, comorbidities, prior cardiothoracic surgery, smoking history, disease staging) with time to surgery (≤8 weeks “on-time” vs. >8 weeks “delayed”). ResultsFifty-one patients underwent esophagectomy within 8 weeks of chemoradiation; 45 had a delayed operation. Univariate analysis showed the following characteristics were significantly different between on-time and delayed groups: weight loss within 3 months of surgery (3.9 ± 5.1 kg vs. 1.5 ± 3.6 kg; P = 0.009), prior cardiovascular disease (29% vs. 49%; P = 0.05), prior cardiothoracic surgery (4% vs. 22%; P = 0.01), history of ever smoked (69% vs. 87%; P = 0.04), absent nodal metastasis on pathology (57% vs. 82%; P = 0.008). Multivariate analysis demonstrated that prior cardiothoracic surgery (OR 8.924, 95%CI 1.67–47.60; P = 0.01) and absent nodal metastasis (OR 4.186, 95%CI 1.50–11.72; P = 0.006) were associated with delayed surgery. ConclusionsDelayed esophagectomy following chemoradiotherapy is associated with prior cardiothoracic surgery and absent nodal metastasis. Further investigations should focus on understanding how these factors contribute to delays to guide treatment planning and mitigate sources of outcome disparities.

Early versus delayed surgery following neoadjuvant chemoradiation for esophageal cancer: a systematic review and meta-analysis.

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery, is the mainstay of managing locally advanced esophageal cancer. However, the optimal timing of surgery after neoadjuvant therapy is not defined clearly. A systematic search of PubMed, Embase and Cochrane databases was conducted. 6-8weeks were used as a cut-off to define early and delayed surgery groups. Overall Survival (OS) was the primary outcome, whereas pathological complete resolution (pCR), R0 resection, anastomotic leak, perioperative mortality, pulmonary complications, and major complication (> Clavien-Dindo grade 2) rates were secondary outcomes. Cohort studies and national registry bases studies were analysed separately. Survival data were pooled as Hazard Ratio (HR) and the rest as Odds Ratio (OR). According to heterogeneity, fixed-effect or random-effect models were used. Twelve retrospective studies, one RCT, and six registry-based studies (13,600 participants) were included. Pooled analysis of cohort studies showed no difference in OS (HR 1.03, CI 0.91-1.16), pCR (OR 0.98, CI 0.80-1.20), R0 resection (OR 0.90, CI 0.55-I.45), mortality (OR 1.03, CI 0.59-1.77), pulmonary complications (OR 1.26, CI 0.97-1.64) or major complication rates (OR 1.29, CI 0.96-1.73). Delayed surgery led to increased leak (OR 1.48, CI 1.11-1.97). Analysis of registry studies showed that the delayed group had a better pCR rate (OR 1.12, CI 1.01-1.24), with no improvement in survival (HR 1.01, CI 0.92-1.10). Delayed surgery was associated with increased mortality (OR 1.35, CI 1.07-1.69) and major complication rate (OR 1.55, CI 1.20-2.01). Available RCT reported surgical outcomes only. National registry-based studies' analysis shows that delay in surgery is riskier and leads to higher mortality and major complication rates. Further, well-designed RCTs are required.

Neoadjuvant chemoradiation in elderly Irish patients with esophageal cancer: A review of the clinical outcomes and toxicity.

335 Background: In locally advanced esophageal cancer, neoadjuvant chemo-radiotherapy improves survival compared with surgery alone. In the Chemo-Radiotherapy for Oesophageal cancer followed by Surgery Study (CROSS), the median age was 60. However, 1/3 of patients diagnosed with esophageal cancer are over 70 years. The CROSS outcomes are therefore limited in its application to older patients. The objective of this study is to report and compare the outcomes and tolerability in elderly patients (≥70 years), who underwent neoadjuvant chemo-radiation for esophageal cancer with younger patients < 70 years. Methods: A retrospective analysis of patients treated with neoadjuvant chemo-radiation for esophageal cancer between 1st January 2015 and 1st January 2021 was completed. Baseline characteristics and haematological toxicities were reported. Pathological response was reported. Survival was estimated using the Kaplan-Meier method. Results: In total 105 patients were included; 35 (33%) were ≥ 70 years and 70 (67%) patients were < 70 years. In the elderly cohort, the median age was 75 (70-86) and the younger cohort median age was 60 (29-69). 73% of patients in each cohort were male. 31 (89%) of older adults experienced any grade of anaemia compared with 45 (64%) of the younger cohort. Only one patient experienced ≥ grade 3 anaemia in each cohort. 18(51%) and 33(47%) of older and younger patients respectively experienced any grade of neutropenia. 5(14%) older and 7(10%) younger patients experienced ≥ grade 3 neutropenia. 15(43%) and 43(61%) of older and younger patients experienced any grade of thrombocytopenia. No patients experienced ≥ grade 3 thrombocytopenia. 80% of the older and 86% of the younger cohort proceeded to surgery. 3(11%) and 17(29%) of the older and younger cohorts respectively who underwent surgery achieved a complete pathological response. There was no difference in overall survival (OS) between the cohorts (p=0.48). There was also no difference in progression free survival (PFS) between the cohorts. Conclusions: In conclusion, we confirm that neoadjuvant chemo-radiation is tolerable in patients ≥ 70 when compared with patients < 70 years. Both OS and PFS is similar in both cohorts. We recommend the use of neoadjuvant therapy in appropriately selected patients ≥ 70 years.

Early versus delayed surgery following neoadjuvant chemoradiation for esophageal Cancer: A systematic review and meta-analysis

Early versus delayed surgery following neoadjuvant chemoradiation for esophageal Cancer: A systematic review and meta-analysis

Estrogen-related receptor alpha drives mitochondrial biogenesis and resistance to neoadjuvant chemoradiation in esophageal cancer

Neoadjuvant chemoradiotherapy (nCRT) improves outcomes in resectable esophageal adenocarcinoma (EAC), but acquired resistance precludes long-term efficacy. Here, we delineate these resistance mechanisms. RNA sequencing on matched patient samples obtained pre-and post-neoadjuvant treatment reveal that oxidative phosphorylation was the most upregulated of all biological programs following nCRT. Analysisof patient-derived models confirms that mitochondrial content and oxygen consumption strongly increase in response to nCRT and that ionizing radiation is the causative agent. Bioinformatics identifies estrogen-related receptor alpha (ESRRA) as the transcription factor responsible for reprogramming, andoverexpression and silencing of ESRRA functionally confirm that its downstream metabolic rewiring contributes to resistance. Pharmacological inhibition of ESRRA successfully sensitizes EAC organoids and patient-derived xenografts to radiation. In conclusion, we report a profound metabolic rewiring following chemoradiation and demonstrate that its inhibition resensitizes EAC cells to radiation. These findings hold broader relevance for other cancer types treated with radiation as well.

A Deep Learning Classifier Based on Pre-Radiation Computed Tomography and Clinical Parameters to Predict Pathological Complete Response after Neoadjuvant Chemoradiation in Esophageal Cancer

<h3>Purpose/Objective(s)</h3> Neoadjuvant chemoradiation (NCRT) followed by surgery is the standard treatment for resectable esophageal cancer. More than 30% patients achieve pathological complete response (pCR) after NCRT, who may avoid the followed surgery. However, there is no reliable method in predicting pCR yet. Artificial intelligence, especially deep learning, has made great progress in many fields including treatment response prediction. Therefore, we built up a deep learning classifier based on pre-radiation computed tomography and clinical parameters to predict pCR after NCRT for esophageal cancer. <h3>Materials/Methods</h3> Between 2009 and 2021, consecutive patients with esophageal cancer received NCRT and complete resection were retrospectively analyzed. Pathological response assessed on surgical specimen was collected. Patients were randomly assigned to the training set, validation set, and testing set as 7: 1: 2. We built a binary classification neural network based on 3D Resnet. Pre-radiation computed tomography (CT) was fed as input to build the imaging classifier. The filtered clinical parameters including gender, tumor location, clinical stage, pathological type, sequence of chemoradiation, chemotherapy regimen and radiotherapy technique were then added by encoded as fully connected layer to build the combined classifier. Area under the receiver operating characteristic curve (AUC) was calculated to evaluate the prediction performance and the optimal cut-off point was determined by Youden index. <h3>Results</h3> Totally 279 patients were enrolled, of whom 93 achieved pCR (33.3%). The performances of imaging classifier were AUC=0.989 (95% CI 0.937-0.986) with the sensitivity of 98.6% and specificity of 98.5% in the training set, and AUC=0.649 (95% CI 0.481-0.660) with the sensitivity of 66.7% and specificity of 58.9% in the testing set, respectively. After the addition of clinical parameters, the combined classifier showed AUC=0.855 (95% CI 0.797-0.986) with the sensitivity of 82.4% and specificity of 74.3% in the training set, and AUC=0.731 (95%CI 0.631-0.819) with the sensitivity of 76.6% and specificity of 65.6% in the testing set, respectively. <h3>Conclusion</h3> The combined deep learning classifier can accurately predict pCR after NCRT for esophageal cancer. Besides, addition of necessary clinical parameters can remedy the overfitting of imaging classifier. Prospective exploration based on larger data sets is needed to further improve the accuracy and generalization.

Can Clinical Response Predict Pathologic Response Following Neoadjuvant Chemoradiation for Esophageal Cancer?

ObjectivesApproximately 20–40% of patients with locally advanced esophageal cancer will achieve a pathologic complete response (ypCR) following neoadjuvant chemoradiotherapy (nCRT). Predicting ypCR based on a clinical complete response (ycCR) has been a challenge. This study assessed the correlation between ycCR and ypCR, as determined from esophagectomy specimens. MethodsPatients undergoing esophagectomy following nCRT at three major institutions between 2005 and 2018 were reviewed. Restaging, including PET/CT, endoscopy with biopsy, and esophageal ultrasound (EUS), was performed to determine ycCR. ResultsSix hundred sixty patients were included, with 93.3% with esophageal adenocarcinoma histology. Six hundred fifty-eight of these patients underwent PET, 304 EUS, and 584 underwent a biopsy. Following nCRT, 148 (22.4%) were found to have a ypCR. Only 12/32 (37.5%) determined to have a ycCR were found to have a ypCR, while 136/628 (21.6%) with a non-ycCR were found to have a ypCR (p 0.075). Individual modality PPV was 28% for PET, 54% for EUS, and 26% for biopsy. When PET was combined with EUS, 168 reports were concordant and the PPV of ypCR was 50%, though the number of patients was low (1/2). With all 3 re-staging modalities combined, the PPV and NPV both rose to 100%. ConclusionsCurrent restaging tools cannot reliably predict ypCR after nCRT. While multimodal restaging appears to be a more accurate predictor of ypCR than any testing modality alone, patients cannot reliably be advised to avoid an esophagectomy on the assumption that ycCR predicts ypCR at this time.

PO-1528: Predicting response to neoadjuvant chemoradiation in esophageal cancer using CT radiomic features

PO-1528: Predicting response to neoadjuvant chemoradiation in esophageal cancer using CT radiomic features

Dosimetric analysis of lymphopenia during chemoradiotherapy for esophageal cancer.

BackgroundLymphopenia during chemoradiation (CRT) for esophageal cancer (EC) can adversely affect clinical outcomes. We sought to explore an association between lymphopenia and dosimetric parameters during CRT for EC.MethodsAfter IRB approval, we retrospectively reviewed 54 patients treated with either definitive or neoadjuvant CRT for EC. Absolute lymphocyte count was recorded weekly during CRT up and graded according to the common terminology of adverse events (CTCAE) version 4.0. Dose volume histograms (DVH) parameters were collected based on vertebral body, body dose, dose to peripheral lymphocytes, and spleen. Logistic regression correlated Grade 4 toxicity with DVH parameters and linear regression analysis correlated absolute lymphocyte nadir counts with DVH parameters. Receiver operator curves (ROC) were constructed to define dosimetric thresholds.ResultsThere were a total of 21 Grade 4 events (38.8%) of lymphopenia. Increasing vertebral volume receiving ≥10 Gy (OR 1.1, P=0.04), ≥20 Gy (OR 1.1, P=0.03), ≥30 Gy (OR 1.1, P=0.012), or mean body dose (OR 1.04, P=0.032) were correlated with Grade 4 lymphopenia on multivariable logistic regression. The dosimetric parameters most predictive of Grade 4 toxicity via a ROC analysis included absolute vertebral volume receiving 10 Gy >289 cc, 20 Gy ≥270 cc, and vertebral volumes receiving 30 Gy ≥197 cc. On multivariable linear regression increasing volume receiving 20 Gy (Beta −0.004, P=0.001), 30 Gy (Beta −0.005, P=0.0046), and mean body dose (Beta −0.002, P=0.001) all correlated with absolute lymphocyte nadir.ConclusionsLymphopenia, a known negative prognostic factor in EC, is closely correlated with the volume of vertebral bodies receiving radiation during CRT for EC. Dosimetric sparing of the vertebral bodies may result in better outcomes.

Drivers of 30- and 90-day Postoperative Death After Neoadjuvant Chemoradiation for Esophageal Cancer

Neoadjuvant chemoradiation, followed by esophagectomy, is a standard of care for locally advanced esophageal cancers. The ChemoRadiOtherapy plus Surgery versus Surgery alone (CROSS) trial reported a 30-day mortality rate of 6%. We sought to evaluate 30- and 90-day mortality in similar patients in the United States and identify predictors of higher mortality rates. The National Cancer Database was used to identify patients with cT3-4/N+ esophageal cancers treated with neoadjuvant chemoradiation followed by esophagectomy. Bivariate univariable and multivariable regression analysis was used to identify predictors of 30- and 90-day mortality. We identified 7691 patients. Readmission within 30 days of surgery occurred in 6.0% of patients. Mortality was 2.9% at 30 days and 7.2% at 90 days. Positive surgical margins conferred a more than doubled risk of 30- and 90-day mortality, 5.5% vs 2.7% and 14.6% vs6.8% (both P < .001). Facility surgical volume impacted 30-day mortality, whereas readmission was associated with 90-day mortality, both exceeding 10% (P= .004 and P= .001, respectively). In patients undergoing minimally invasive surgery converted to open, 90-day mortality was 12.1% (P < .01). For patients 69 years and older, 90-day mortality was also 12.1% (P < .001). Patients who underwent esophagectomy more than 45 days from completion of chemoradiation also had higher 90-day mortality at 8.3% vs 6.2% (P < .001). Postoperative death at 30 and 90 days after neoadjuvant chemoradiation and esophagectomy appears to be on par with randomized data. Positive surgical margins, squamous cell carcinomas, age 69 and older, readmission within 30 days, and conversion from a minimally invasive operation to an open operation all carry a 90-day mortality risk exceeding 10%.

Drivers of 30-/90-Day Post-Operative Mortality Following Neoadjuvant Chemoradiation for Esophageal Cancer

Drivers of 30-/90-Day Post-Operative Mortality Following Neoadjuvant Chemoradiation for Esophageal Cancer

Comparison of Pathologic Complete Response Rates and Outcomes in Patients Receiving Neoadjuvant Chemoradiation to 50.4Gy Vs 41.4 Gy in the Treatment of Surgically Resectable Esophageal Cancer

The CROSS trial reported high rates of pathological complete response (pCR) and excellent outcomes with neoadjuvant chemoradiation for esophageal cancer with carboplatin and paclitaxel despite treating to only 41.4 Gy. With pCR rates comparable to historical series using 50.4 Gy, the question arises if there is any advantage to a higher dose in this population. This study compares pCR rates and outcomes in patients treated with 41.4 Gy vs 50.4 Gy in the neoadjuvant setting. We retrospectively reviewed the records of patients with esophageal adenocarcinoma (AC) or squamous cell carcinoma (SCC) treated with neoadjuvant chemoradiation with carboplatin/paclitaxel who underwent surgical resection. The primary endpoint was pCR rate. Secondary endpoints were progression free survival (PFS) and overall survival (OS). Groups were compared with Fischer exact test and t-test. Kaplan-Meier method was used to calculate PFS and OS with comparisons made with the log rank test. We identified a total of 33 patients treated with neoadjuvant chemoradiation followed by oncologic resection. 16 patients were treated with 41.4 Gy and 17 with 50.4 Gy. Cohorts were well matched with regard to age, clinical stage, tumor grade, ECOG performance status, and smoking history (all p>0.05). There were significantly higher frequencies of adenocarcinoma (13/16 vs 6/17) (p=0.007), lower-third of the esophagus primary (15/16 vs. 9/17) (p=0.026), and use of IMRT (11/16 vs. 5/17) (p<0.001)in the 41.4 Gy cohort vs 50.4 Gy. There was no difference in pCR rates (7/16 (43.8%) vs 8/17 (47.1%), p=0.563) between patients receiving 41.4 vs 50.4 Gy, respectively, even when correcting for AC vs. SCC. At a median follow up of 28 months, there was no difference in 3-year OS (73.3% vs 71.4% p=.21) or 3-year PFS (47.4% vs 35.4%, p=.237) between 50.4 Gy and 41.4 Gy, respectively. In this series of esophageal cancer treated with neoadjuvant chemoradiation with carboplatin/paclitaxel followed by surgical resection, there appears to be no difference in pCR between 41.4 Gy and 50.4 Gy as well as no difference in PFS and OS. Larger, multi-institutional series are needed to validate these results.

1031 – Lymphadenectomy and Survival After Neoadjuvant Chemoradiation for Esophageal Cancer: is More Better?

1031 – Lymphadenectomy and Survival After Neoadjuvant Chemoradiation for Esophageal Cancer: is More Better?

Patients with Non-response to Neoadjuvant Chemoradiation for Esophageal Cancer Have No Survival Advantage over Patients Undergoing Primary Esophagectomy

BackgroundSurvival for patients with locally advanced esophageal cancer remains dismal. Non-response to neoadjuvant chemoradiation (nCRT) portends worse survival. We hypothesized that patients undergoing up-front esophagectomy may have better survival than those who do not respond to nCRT. MethodsWe identified all patients undergoing esophagectomy with a pathologic stage of II or greater at our institution between 1994 and 2015 and separated them into two groups: those who received nCRT and those undergoing up-front esophagectomy. The neoadjuvant group was further separated into patients downstaged to pathologic stage 0 or I (responders) and patients with either the same or higher pathologic stage after nCRT, or with pathologic stage II disease or greater (non-responders). Overall survival was compared between groups using Kaplan–Meier statistics. Covariate-adjusted Cox modeling was used to estimate hazard ratios (HR) for mortality associated with non-response. ResultsOverall, 287 patients met inclusion criteria. Fifty-nine percent of the responders had pathologic complete response (pCR). The majority of non-responders and primary esophagectomy patients had stage II or III disease (94%). Median survival was 58.3 months in responders, 23.9 months in non-responders, and 29.1 months in primary esophagectomy patients (p < 0.01). The HR for mortality associated with non-response was 1.82 compared to response to nCRT (p < 0.01) and 1.09 compared to primary esophagectomy (p = 0.71). ConclusionsIn patients with esophageal cancer who do not respond to nCRT, neoadjuvant therapy may represent a toxic and costly treatment modality that does not improve survival and may delay potentially curative resection. Further research is needed to identify potential non-responders with advanced resectable disease and allow individual tailoring of pre-surgical decision-making.

Dose-Dependent Association of Vertebral Body irradiation and Lymphopenia During Chemoradiation for Esophageal Cancer

Lymphopenia during chemoradiation (CRT) for esophageal cancer (EC) can adversely affect clinical outcomes. Treatment related factors associated with lymphopenia in this population are not well defined. We hypothesized that radiation dose to vertebral bone marrow during chemoradiotherapy for EC was associated with lymphopenia. The goal of our study was to investigate the dosimetric relationship between vertebral irradiation and lymphopenia. We further sought to explore the association between missed chemotherapy events and hematological toxicity. With institutional review board approval, we retrospectively reviewed forty patients treated with either conventionally fractionated definitive or neoadjuvant CRT for EC. Patients were excluded if treated with palliative intent. Absolute lymphocyte count (ALC) was recorded weekly until two weeks following CRT and graded according to the common terminology of adverse events (CTCAE) version 4.0. Dose volume histogram (DVH) parameters were collected based on vertebral volume receiving between 10 and 40 Gy. Logistic regressions correlated Grade 4 toxicity with DVH parameters and linear regression analysis correlated absolute lymphocyte count nadir with DVH parameters. Receiver Operator Curves (ROC) were constructed to further define dose volume parameters associated with toxicity. Wilcoxon rank sum test and chi-squared analyses tested the association between missed chemotherapy for both Grade 4 lymphopenia and absolute lymphocyte nadir. There were a total of 21 (52.5%) Grade 3 (ALC <0.5 x 109/L) and 17 (42.5%) Grade 4 (ALC <0.2 x 109/L) lymphopenic events. Vertebral volume (VVERT) receiving ≥10 Gy (OR 1.015, p=0.02), ≥20 Gy (OR 1.018, P = 0.025), and ≥30 Gy (OR 1.012, p = 0.026) were correlated with Grade 4 lymphopenia on multivariable logistic regression. Multivariable linear regression correlated lymphopenia nadir with VVERT receiving ≥20 Gy (OR 0.99, P = 0.01), ≥30 Gy (OR 0.99, P = 0.01), and ≥40 Gy (OR 0.99, P = 0.01). Dosimetric parameters on ROC most predictive of Grade 4 toxicity included vertebral volume receiving 10 Gy (VVERT10) ≥291 cc, VVERT20 ≥278 cc, and VVERT30 ≥193 cc. Grade 4 lymphopenia, and lymphocyte nadir were associated with missed chemotherapy (p = 0.01 and p < 0.002, respectively). Lymphopenia, a known negative prognostic factor for EC, is associated with greater volume of vertebral bodies receiving radiation during CRT. Dosimetric sparing of the vertebral bodies may result in less immunosuppression, better tolerance of CRT, and improved clinical outcomes, warranting further investigation.

YpT0N+: the unusual patient with pathological complete tumor response but with residual lymph node disease after neoadjuvant chemoradiation for esophageal cancer, what's up?

Little is known about the prognostic significance of residual nodal disease in otherwise complete pathologic responders (ypT0N+) after neoadjuvant chemoradiation (nCRT) for esophageal cancer (EC). The purpose is to analyze the long-term outcomes of EC patients with ypT0N+ following nCRT and esophagectomy. From a single institution database, 466 consecutive EC patients undergoing esophagectomy after nCRT were collected (1996-2016). ypT0N+ responders were compared to pathological complete responders (ypT0N0) and to pathological non-complete responders (ypT+N0 and ypT+N+). There were 149 ypT0N0, 31 ypT0N+, 141 ypT+N0 and 145 ypT+N+. Median overall survival (OS) was worse in ypT0N+ (21.7 months) and ypT+N+ (16.8 months) compared to ypT0N0 (55.2 months) and ypT+N0 (42.0 months). Stratification by histology revealed a significant difference in prevalence of ypT0: 62.5% in 184 squamous cell carcinomas (SCC) compared to 23.0% in 282 adenocarcinomas (ADC) (P<0.0001) but not in ypT0N+ (15% vs. 22% respectively, P=0.25). In ADC, locoregional recurrence in ypT0N+ (43%) was comparable to ypT+N+ (31%) and more common compared to ypT0N0 (7%) and ypT+N0 (10%), reflected in median OS rates of 20.6, 17.5, 53.0 and 36.6 months respectively. Median OS in ADC is significantly determined by number of positive lymph nodes, being 21.7 months for pN1 and 2.7 months for pN2/3 (P=0.005) in ypT0N+ and 33.7 months for pN1 and 16.2 months for pN2/3 (P=0.031) in ypT+N+. In SCC, locoregional recurrences were found in 17% of ypT0N+, 33% of ypT+N+, 11% of ypT0N0 and 22% in ypT+N0 and median OS was 26.6, 15.6, 55.2 and 43.8 months respectively. In SCC ypN+ number of affected lymph nodes showed no difference on OS. ypT0N+ in EC patients following nCRT has a poor prognosis and behaves similar to ypT+N+. However, stratification by histology shows that this is especially true in ADC but seems determined by the number of involved lymph nodes.

Complete pathologic response is independent of the timing of esophagectomy following neoadjuvant chemoradiation for esophageal cancer

The relationship of complete pathologic response (cPR) with the timing of esophagectomy after neoadjuvant chemoradiation (nCRT) is not well defined. We sought to determine if a delay in esophagectomy after nCRT would result in increased likelihood of cPR and improved survival. This is a retrospective analysis of a prospectively maintained database of all patients treated with nCRT and esophagectomy between 2004 and 2014. Patients were divided into two groups based on timing of esophagectomy (≤50 vs. >50 days) after completion of nCRT. Survival outcomes were compared using standard Kaplan-Meier curves, and multivariable analyses were performed using Cox regression models. This study included 226 patients (males, 211 and median age, 61 years) for analysis. Fifty-two patients (23%) in the early group (≤50 days) were compared to 174 patients (77%) in the delayed group (>50 days). The two groups were similar with respect to age, gender, comorbid conditions, ECOG status, location, grade, and tumor histology. There was no statistically significant difference in cPR rate between the early and late groups (26.9% vs. 19.0%, respectively, P=0.24). On multivariable analysis, lower age, absence of signet cell histology, better ECOG status, shorter length of stay and cPR were independent predictors of improved survival. The median follow-up was 52 months (range, 2-110 months), and there was no difference in the median overall survival (OS) between the early and late groups (48.9 vs. 42.6 months, respectively, P=0.73). This analysis of a large cohort of patients with esophageal cancer undergoing multi-modality therapy shows that cPR is independent of the timing of esophagectomy. Other considerations for the timing of surgery, including recovery from nCRT and patient performance, may have more relevant roles than cPR when deciding when to perform esophagectomy.

Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy

Background and purposeCirculating lymphocytes are exquisitely sensitive to radiation exposure, even to low scattered doses which can vary drastically between radiation modalities. We compared the relative risk of radiation-induced lymphopenia between intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT) in esophageal cancer (EC) patients undergoing neoadjuvant chemoradiation therapy (nCRT). Material and methodsEC patients treated with IMRT and PBT were propensity matched based on key clinical variables. Treatment-associated lymphopenia was graded using CTCAE v.4.0. Using matched cohorts, univariate and multivariable multiple logistic regression was used to identify factors associated with increased risk of grade 4 lymphopenia as well as characterize their relative contributions. ResultsAmong the 480 patients treated with nCRT, 136 IMRT patients were propensity score matched with 136 PBT patients. In the matched groups, a greater proportion of the IMRT patients (55/136, 40.4%) developed grade 4 lymphopenia during nCRT compared with the PBT patients (24/136, 17.6%, P < 0.0001). On multivariable analysis, PBT was significantly associated with a reduction in grade 4 lymphopenia risk (odds ratio, 0.29; 95% confidence interval, 0.16–0.52; P < 0.0001). ConclusionPBT is associated with significant risk reduction in grade 4 lymphopenia during nCRT in esophageal cancer.

Preoperative enteral access is not necessary prior to multimodality treatment of esophageal cancer

BackgroundSurgical enteral access prior to multimodality treatment for esophageal cancer is controversial as dysphagia is often used for feeding tube referral. We hypothesized that enteral access before neoadjuvant chemoradiation for esophageal cancer provides no benefit compared to that placed during definitive esophagectomy. MethodsPatients undergoing esophagectomy for esophageal malignancy from 2007 − 2014 were retrospectively identified. Clinicopathologic factors were recorded including preoperative enteral access, weight change, nutritional laboratory works, and perioperative complications. ResultsOf 156 identified patients, 99 (63.5%) received neoadjuvant chemoradiation and comprised the study cohort. Fifty (50.5%) underwent enteral access (gastrostomy [14], jejunostomy [32], other [4]; “Access Group”) prior to chemoradiation followed by esophagectomy and were compared to 49 “No-Access” patients who underwent enteral access during esophagectomy. Clinicopathologic variables were similar between cohorts. The Access and No-Access cohorts had similar reported dysphagia (86% vs 75.5%, respectively; P = .2) and mean preesophagectomy serum albumin (3.9 vs 4 gm/dL, respectively; P = .2). Weight loss ± 6-month periesophagectomy was similar between access versus No-Access cohorts (−11.2% vs −15.4%, respectively; P = .1). Weight loss during this period was likewise similar for patients with dysphagia in the Access (−11%) versus No-Access group (−15.2%, P = .1). No difference in complication rates was noted between Access (64%) and No-Access groups (51%, P = .2). ConclusionDespite healthcare provider bias, there seems to be no nutritional or perioperative benefit for enteral access before neoadjuvant chemoradiation for esophageal malignancy. Patients with esophageal malignancy should therefore proceed to appropriate neoadjuvant and surgical therapy with enteral access performed during definitive resection or reserved for those with frank obstruction on endoscopy.