scholarly journals Complete Pathologic Response Predicts Disease-Free Survival for Melanoma Patients Undergoing Neoadjuvant Therapy

2021 ◽  
Vol 233 (5) ◽  
pp. S246
Author(s):  
Kristen E. Rhodin ◽  
Elizabeth M. Gaughan ◽  
Vignesh Raman ◽  
April K. Salama ◽  
Brent A. Hanks ◽  
...  
2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Alexis Legault-Dupuis ◽  
Philippe Bouchard ◽  
Frederic Nicodème ◽  
Jean-Pierre Gagne ◽  
Serge Simard ◽  
...  

Abstract   The treatment of esophageal cancer is in constant evolution. Most of the esophageal cancer receive induction chemoradiation therapy. Surgical delay has been studied but the optimal timing has not been clarified. Through the years, surgical delay has been modified by surgeons in our institutions, going from an average of 6 weeks delay to an average of 10 weeks delay. It is time to ask if this change has a real positive impact on our patient. Methods In this retrospective multi-center study, we combined data from two center in Quebec city that performs oncologic esophagectomy. The surgical delay went from 6 to 10 weeks around 2014. All surgeons changed their practice at that moment. We retrospectively analysed 5 years before and after the change of practice and created two cohorts of patients. Our primary outcome compared complete pathologic response rate. Our secondary outcomes were surgical complications, anastomotic leak, disease free survival and overall survival. Results Thirty-eight patients had surgery under 8 weeks (mean: 6 weeks) after their induction chemoradiation compared to 64 patients that had surgery after 8 weeks (mean: 10 weeks). There was no statistical significant difference between groups for the complete pathologic response (32% vs 25%, p = 0,16). Important complications were similar, with a rate of 24% vs 28% (p = 0,69). Anastomotic leaks were less frequent in the less than 8 weeks group, but no statistical significance was obtained (13% vs 27%, p = 0,14).No difference in the disease-free survival rate and overall survival rate was noted (DFS 40% vs 55% (p = 0,32), OS 38% vs 38% (p = 0,29)). Conclusion The treatment of esophageal cancer is in constant evolution, induction therapy and surgical technics involve over time. Surgical delay has no impact on complete pathologic response, complication and overall survival. There is no advantage to wait longer before surgery.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 130-130
Author(s):  
K. Meredith ◽  
J. Weber ◽  
R. Shridhar ◽  
S. E. Hoffe ◽  
K. Almhanna ◽  
...  

130 Background: Esophageal cancer often presents as locally advanced disease with 15% of patients having T4 tumors upon diagnosis. Esophagectomy was often reserved for palliation given the dismal survival rates and high rates of R1/R2 resections. However, neoadjuvant therapy (NT) has the potential to significantly downstage esophageal cancers and thus increase complete resection rates. We report our experience with surgically resected T4 cancers of the esophagus. Methods: Using a comprehensive esophageal cancer database, we identified patients who underwent an esophagectomy for T4 tumors between 1994 and 2008. Neoadjuvant therapy and pathologic response were recorded and denoted as complete (pCR), partial (pPR), and non-response (NR). Clinical and pathologic data were compared using Fisher's exact and chi-square when appropriate while Kaplan Meier estimates were used for survival analysis. Results: We identified 39 patients with T4 tumors who underwent esophagectomy of which 38 (97%) underwent NT. The median age was 61 (31-79) years with a median follow-up of 32 (5-97) months. There were 3 (7.9%) pCR, 17 (44.7%) pPR, and 18 (47.4%) NR. R0 resections were accomplished in 37 (94.9%). Two patients had incomplete resections. One patient had a R2 resection after NT and was deemed as NR. An additional patient had a R1 resection after NT and was a pPR with a residual 0.2 cm tumor on permanent pathology. There were 14 (35.9%) recurrences with a median time to recurrence of 19.5 (4-71) months. Complete pathologic response represented 1 (7.1%), whereas pPR and NR represented 6 (42.9%), and 7 (50%) respectively of all recurrences. The overall and disease free survival for all patients with T4 tumors was 28% and 34% respectively. Patients achieving a pCR had a 5-year overall and disease free survival of (43% and 47%), compared to pPR (30% and 21%) while there were no 5-year survivors in the NR cohort. Conclusions: T4 esophageal cancer often portends a dismal prognosis even after surgical resection. Historical incomplete resections and dismal survival rates often make surgery palliative rather then curative. However, we have demonstrated that neoadjuvant therapy and down staging of T4 tumors leads to increased R0 resections and improvements in overall and disease free survival. No significant financial relationships to disclose.


2009 ◽  
Vol 27 (31) ◽  
pp. 5124-5130 ◽  
Author(s):  
Mark S. Roh ◽  
Linda H. Colangelo ◽  
Michael J. O'Connell ◽  
Greg Yothers ◽  
Melvin Deutsch ◽  
...  

Purpose Although chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma. Patients and Methods Patients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS). Results From August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P = .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P = .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence. Conclusion Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.


2021 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Alexis Legault-Dupuis ◽  
Philippe Bouchard ◽  
Frederic Nicodeme ◽  
Jean-Pierre Gagne ◽  
Serge Simard ◽  
...  

Abstract   The treatment of esophageal cancer is in constant evolution. Most of the esophageal cancer receive induction chemoradiation therapy. Surgical delay has been studied but the optimal timing has not been clarified. Through the years, surgical delay has been modified by surgeons in our institutions, going from an average of 6 weeks delay to an average of 10 weeks delay. It is time to ask if this change has a real positive impact on our patient. Methods In this retrospective multi-center study, we combined data from two center in Quebec city that performs oncologic esophagectomy. The surgical delay went from 6 to 10 weeks around 2014. All surgeons changed their practice at that moment. We retrospectively analysed 5 years before and after the change of practice and created two cohorts of patients. Our primary outcome compared complete pathologic response rate. Our secondary outcomes were surgical complications, anastomotic leak, disease free survival and overall survival. Results Thirty-eight patients had surgery under 8 weeks (mean: 6 weeks) after their induction chemoradiation compared to 64 patients that had surgery after 8 weeks (mean: 10 weeks). There was no statistical significant difference between groups for the complete pathologic response (32% vs 25%, p = 0,16). Important complications were similar, with a rate of 24% vs 28% (p = 0,69). Anastomotic leaks were less frequent in the less than 8 weeks group, but no statistical significance was obtained (13% vs 27%, p = 0,14). No difference in disease-free survival rate and overall survival rate was noted (DFS 40% vs 55% (p = 0,32), OS 38% vs 38% (p = 0,29)). Conclusion The treatment of esophageal cancer is in constant evolution, induction therapy and surgical technics involve over time. Surgical delay has no impact on complete pathologic response, complication and overall survival. There is no advantage to wait longer before surgery.


Epigenomics ◽  
2020 ◽  
Vol 12 (19) ◽  
pp. 1689-1706
Author(s):  
Maurizio Cardelli ◽  
Remco van Doorn ◽  
Lares Larcher ◽  
Michela Di Donato ◽  
Francesco Piacenza ◽  
...  

Aim: To evaluate CpG methylation of long interspersed nuclear elements 1 (LINE-1) and human endogenous retrovirus K (HERV-K) retroelements as potential prognostic biomarkers in cutaneous melanoma. Materials & methods: Methylation of HERV-K and LINE-1 retroelements was assessed in resected melanoma tissues from 82 patients ranging in age from 14 to 88 years. In addition, nevi from eight patients were included for comparison with nonmalignant melanocytic lesions. Results: Methylation levels were lower in melanomas than in nevi. HERV-K and LINE-1 methylation were decreased in melanoma patients with clinical parameters associated with adverse prognosis, while they were independent of age and gender. Hypomethylation of HERV-K (but not LINE-1) was an independent predictor of reduced disease-free survival. Conclusion: HERV-K hypomethylation can be a potential independent biomarker of melanoma recurrence.


2021 ◽  
Vol 113 (1) ◽  
pp. 32-42
Author(s):  
Martín Galvarini Recabarren ◽  
◽  
Francisco Schlottmann ◽  
C. Agustín Angeramo ◽  
Javier Kerman Cabo ◽  
...  

Background: Gastric adenocarcinoma (GAC) and esophageal adenocarcinoma (EAC) are one of the leading causes of mortality from gastrointestinal cancer worldwide. Endoscopic ultrasound (EUS) has proved to be a valuable tool for preoperative staging of GAC and EAC in selected cases. Objective: The aim of this study was to evaluate the usefulness of EUS for staging of EAC and GAC and selecting patients who are candidates for neoadjuvant therapy, as compared with the previous stage before the implementation of EUS, in a surgical center in Argentina. Material and methods: Consecutive patients with EAC and GAC between 2013-2019 were included. Patients with criteria of unresectable cancer or who underwent emergency surgery were excluded. The sample was divided into four groups G1 and G2 (EAC with and without EUS, respectively) and G3 and G4 (GAC with and without EUS, respectively). The clinical and anatomopathological variables and survival were evaluated in all the groups. Results: A total of 89 patients were included, 40 with EAC (30 in G1 and 10 in G2, and 49 with GAC, 20 in G3 and 29 in G4. Of the patients undergoing EUS staging in G1, 23 (75%) received neoadjuvant therapy vs. 2 patients in G2 (20%) (P ≤ 0.005). Eight patients (40%) in G3 and 2 (7%) in G4 received perioperative chemotherapy (P ≤ 0.005). Lymph node metastases were observed in 9 (30%) of surgical specimens of EAC in G1 and in 60% in G2 (P ≤ 0.005), and in 45% in G3 and G4. After a mean follow-up of 36 months (6-72), we observed a non-significant trend toward higher overall survival and disease-free survival in patients undergoing EUS staging. Conclusion: EUS for preoperative staging pf EAC and GAC is a useful tool. Although the use of EUS use may be a challenging task in many centers in Argentina, future efforts are needed to include this test in selected cases for staging patients with these types of cancers


2020 ◽  
Author(s):  
Yuchun Wei ◽  
Chuqing Wei ◽  
Chen Liang ◽  
Ning Liu ◽  
Zhenhao Fang ◽  
...  

Abstract Background Response of cervical cancer patients to neoadjuvant therapy differs from person to person. It remains unclear whether genetic alterations can predict response to neoadjuvant therapy and disease-free survival in cervical cancer.Methods 62 Chinese patients with stage IB-IIA cervical cancer were included in this study. Pre-treatment tumor tissues were profiled using a targeted next-generation sequencing assay. Genetic alterations were compared with those identified in the Western populations using the TCGA database. Pathological response and disease-free survival (DFS) were evaluated and their correlations with genetic alterations were analyzed.Results Genetic alterations in PIK3CA were prevalent in both Chinese and Caucasian populations. The mutation frequencies of TERT, POLD1, NOS2, and FGFR3 were significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were frequently mutated in Caucasian patients. Germline mutations were identified in 13 out of 62 Chinese patients and 57% of them occurred in DNA repair genes, such as BRCA1/2, TP53 and PALB2. High tumor mutation burden (TMB), TP53 polymorphism (rs1042522) and KEAP1 mutations were found to be associated with poor response to neoadjuvant therapy. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC amplification and TYMS polymorphism were associated with higher relapse rates of cervical cancer.Conclusion The similarity and difference of mutation landscape of Chinese and Caucasian patients suggested genetic background played a role in shaping the architecture of cervical cancer mutations. The associations of mutation feature of cervical cancer with patient response and tumor recurrence risk provided rationale to further validate and explore potential biomarkers for cervical cancer patients.


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