scholarly journals Impact of a Molecular Sequencing Systematic at Diagnosis in Digestive Oncology: Experience of a French Center

2021 ◽  
pp. 1-13
Author(s):  
Bernadette de Rauglaudre ◽  
Bernadette de Rauglaudre ◽  
Emmanuelle Norguet-Monnereau ◽  
Muriel Duluc ◽  
Isabelle Nanni ◽  
...  

Introduction: Tumor-based molecular profiling has increased in the area of precision medicine. Their routine use is still limited by accessibility, cost and availability of tumor material. Materials and Methods: We retrospectively analysed the treatment received and the survival data of patients with digestive cancer who received molecular high-throughput sequencing (NGS) analyses at diagnosis. The primary objective of this single-center study was to compare the overall survival of patients who were treated with molecularly matched therapy with patients who received standard therapy. Median overall survival was calculated from initial disease diagnosis to death. Results: 528 patients were referred to the Digestive Oncology Department of the Timone Hospital in Marseille between January 2018, and November 2020 for management of digestive cancer and received high-throughput molecular sequencing. Among them, 461 patients had a digestive carcinoma (75 of them were excluded because of the presence of a GIST or a neuroendocrine tumor, a digestive localization of extra digestive cancer or the absence of follow-up in our center) and 275 had metastatic disease (synchronous or metachronous). For metastatic patients, actionable molecular alterations were identified in95 patients (43.5%) and for 13 patients (4.7%) a molecularly matched therapy was administered. There was no significant difference in median overall survival between patients who received matched therapy than patients who did not receive molecularly matched therapy (2.89 [95%CI 1.84 - 3.93] vs. 2.86 [95%CI 1.52 - 4.19], p=0.671). Conclusion: This study suggests that high-throughput genomics can improve management of patients. Although these results did not show a benefit in overall survival for tumors who harboured such actionable molecular alterations and who received molecularly matched therapy, than patients who did not receive molecularly matched therapy, they are promising. Randomized trials are needed to confirm that there is a benefit to treating patients with matched therapy based on NGS.

Author(s):  
Li Lian Kuan ◽  
Ashley R. Dennison ◽  
Giuseppe Garcea

Abstract Background The clinical significance of indeterminate pulmonary nodules (IPN) in patients with resectable pancreatic adenocarcinoma (PDAC) is unknown. The rate of detection on IPN has risen due to enhanced staging investigations to determine resectability. IPNs detected on preoperative imaging represent a clinical dilemma and complicate decision-making. Currently, there are no recommendations on the management of IPN. This review provides a comprehensive overview of the current knowledge on the natural history of IPN detected among patients with resectable PDAC. Methods A systematic review based on a search in Medline and Embase databases was performed. All clinical studies evaluating the significance of IPN in patients with resectable PDAC were included. PRISMA guidelines were followed. Results Five studies met the inclusion criteria. The total patient population was 761. The prevalence of IPN reported ranged from 18 to 71%. The median follow-up duration was 17 months. The median overall survival was 19 months. Patients with pre-operative IPN which subsequently progressed to clinically recognizable pulmonary metastases, ranged from 1.5 to 16%. Four studies found that there was no significant difference in median overall survival in patients with or without IPNs. Conclusion This is a first review on the significance of IPN in patients with resectable PDAC. The preoperative presence of IPN does not demonstrate an association with overall survival after surgery. The identification of IPN is a significant finding however it should not preclude patients with resectable PDAC from undergoing curative resection.


1991 ◽  
Vol 9 (3) ◽  
pp. 444-448 ◽  
Author(s):  
M Boccadoro ◽  
F Marmont ◽  
M Tribalto ◽  
G Avvisati ◽  
A Andriani ◽  
...  

The efficacy of alternating vincristine, melphalan (M), cyclophosphamide, prednisone/vincristine, carmustine, doxorubicin, and prednisone (VMCP/VBAP) polychemotherapy was compared with the M and prednisone (MP) regimen as induction treatment in multiple myeloma (MM). Three hundred four MM patients entered this study between March 1983 and July 1986; the analysis was performed in December 1989. The treatment groups did not show significant differences with respect to major prognostic factors. Median overall survival was 33.8 months. In the VMCP/VBAP and MP arms, after 12 induction chemotherapy cycles, 59.0% and 47.3% (P less than .068) of the patients achieved an M component reduction greater than 50%. No significant difference was observed in the two treatment arms in terms of remission duration (21.3 v 19.6 months, P less than .66) and survival (31.6 v 37.0 months, P less than .28). Patients younger than 65 years did not show any advantage from the alternating polychemotherapy. At diagnosis, the plasma cell labeling index (LI) and serum beta-2 microglobulin (beta 2-m) were evaluated in 173 and 183 patients, respectively. A significantly reduced survival was observed for patients with LI greater than or equal to 2% (16.4 months) or beta 2-m greater than or equal to 6 mg/L (20.4 months). Even in these poor-risk subgroups, VMCP/VBAP was not superior to MP.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2002-2002 ◽  
Author(s):  
Erica Hlavin Bell ◽  
Minhee Won ◽  
Jessica L. Fleming ◽  
Aline P. Becker ◽  
Joseph P. McElroy ◽  
...  

2002 Background: This study sought to update the predictive significance of the three WHO-defined molecular glioma subgroups ( IDHwt, IDHmt/noncodel, and IDHmt/codel) in the subset of specimens available for analysis in NRG Oncology/RTOG 9802, a phase III trial of high-risk low-grade gliomas (LGGs) treated with radiation (RT) with and without PCV after biopsy/surgical resection. Notably, this is the first phase III study to evaluate the predictive value of the WHO subgroups in LGGs using prospectively-collected, well-annotated long-term overall survival data, in a post-hoc analysis. Methods: IDH1/2 mutation status was determined by immunohistochemistry and/or next-generation sequencing. 1p/19q status was determined by Oncoscan and/or 450K methylation data. Treatment effects on overall survival (OS) and progression-free survival (PFS) by marker status were determined by the Cox proportional hazard model and tested using the log-rank test in a secondary and exploratory analysis. Results: Of all the randomized eligible high-risk G2 patients (N = 251) in NRG Oncology/RTOG 9802, 106(42%) patients had tissue available with sufficient quality DNA for profiling. Of these, 80(75%) were IDHmut; 43(41%) were IDHmut/non-co-deleted, 37(35%) were IDHmut/co-deleted, and 26(24%) were IDHwt. Upon univariate analyses, no significant difference in either PFS or OS was observed with the addition of PCV in the IDHwt subgroup. Both the IDHmut/non-co-deleted and IDHmut/co-deleted subgroups were significantly correlated with longer PFS (HR = 0.32; p = 0.003; HR = 0.13; p < 0.001) and OS (HR = 0.38; p = 0.013; HR = 0.21; p = 0.029) in the RT plus PCV arm, respectively. Conclusions: Our analyses suggest that both IDHmut/non-co-deleted and IDHmut/co-deleted subgroups received benefit from treatment with PCV although sample size is limited and analyses are post-hoc. Our results also support the notion that IDHwt high-risk LGG patients do not benefit from the addition of PCV to RT. Funding: U10CA180868, U10CA180822, and U24CA196067. Also, R01CA108633, R01CA169368, RC2CA148190, U10CA180850-01, BTFC, OSU-CCC (all to AC). Clinical trial information: NCT00003375.


2014 ◽  
Vol 120 (2) ◽  
pp. 300-308 ◽  
Author(s):  
Adam M. Sonabend ◽  
Brad E. Zacharia ◽  
Hannah Goldstein ◽  
Samuel S. Bruce ◽  
Dawn Hershman ◽  
...  

Object Central nervous system (CNS) hemangiopericytomas are relatively uncommon and unique among CNS tumors as they can originate from or develop metastases outside of the CNS. Significant difference of opinion exists in the management of these lesions, as current treatment paradigms are based on limited clinical experience and single-institution series. Given these limitations and the absence of prospective clinical trials within the literature, nationwide registries have the potential to provide unique insight into the efficacy of various therapies. Methods The authors queried the Surveillance Epidemiology and End Results (SEER) database to investigate the clinical behavior and prognostic factors for hemangiopericytomas originating within the CNS during the years 2000–2009. The SEER survival data were adjusted for demographic factors including age, sex, and race. Univariate and multivariate analyses were performed to identify characteristics associated with overall survival. Results The authors identified 227 patients with a diagnosis of CNS hemangiopericytoma. The median length of follow-up was 34 months (interquartile range 11–63 months). Median survival was not reached, but the 5-year survival rate was 83%. Univariate analysis showed that age and radiation therapy were significantly associated with survival. Moreover, young age and supratentorial location were significantly associated with survival on multivariate analysis. Most importantly, multivariate analysis using the Cox proportional hazards model showed a statistically significant survival benefit for patients treated with gross-total resection (GTR) in combination with adjuvant radiation treatment (HR 0.31 [95% CI 0.01–0.95], p = 0.04), an effect not appreciated with GTR alone. Conclusions The authors describe the epidemiology of CNS hemangiopericytomas in a large, national cancer database, evaluating the effectiveness of various treatment paradigms used in clinical practice. In this study, an overall survival benefit was found when GTR was accomplished and combined with radiation therapy. This finding has not been appreciated in previous series of patients with CNS hemangiopericytoma and warrants future investigations into the role of upfront adjuvant radiation therapy.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1618-1618
Author(s):  
Gaurav Goyal ◽  
Adam C Bartley ◽  
Aref Al-Kali ◽  
William J Hogan ◽  
Mark Litzow ◽  
...  

Abstract Introduction Isolated myeloid sarcoma is a rare form (<1%) of acute myeloid leukemia presenting as extramedullary tumor. Contemporary clinical data are mostly limited to institutional case series. Using the National Cancer Database, the largest public cancer registry covering >70% of all newly diagnosed cancers in the United States, we determined the patterns of anatomical presentation and clinical outcome of myeloid sarcoma. Methods We identified patients with a histologically confirmed diagnosis of isolated myeloid sarcoma from 2004-2013 using International Classification of Diseases for Oncology version 3 (ICD-O-3) code: 9930. To allow at least 1 year of follow-up, only patients diagnosed from 2004-2012 were included in the survival analysis using Kaplan-Meier estimates. Results A total of 746 patients were included in the study. The median age of patients was 59 years (range, 41 to 73) and 56% were males. The anatomical distribution and median overall survival of patients are depicted in the Table. The top 3 most common sites of presentation were connective/soft tissues (31.3%), skin/breast (12.3%), and digestive system (10.3%). Compared to other races, Blacks were more likely to have presentation in bones/joints (11.8% vs 6.3% in others), lymph nodes/spleen (22.1% vs. 9%), and less likely in skin/breast (4.4% vs. 13.8%). Asians were more likely to present with cardiopulmonary/mediastinal disease as compared to other races (13.6% vs. 4.2%). According to outcomes, we can categorize the patients into 3 groups: good (median overall survival >30 months: reproductive and digestive systems), intermediate (median overall survival 15-30 months: head/neck and kidney/bladder/retroperitoneum/adrenal), and poor (median overall survival <15 months: nervous system, connective/soft tissue, and bones/joints). There was no significant difference in overall survival between males and females (P =0.06). Among the races, Blacks had the worst overall survival (P =0.02; Figure). Conclusions This is the largest registry-based study on isolated myeloid sarcoma in the United States. Isolated myeloid sarcoma has a diverse anatomic clinical presentation and the overall survival varied significantly according to sites of presentation and racial subgroups. The results of our study may aid the prognostication of patients for treatment decision making and in the understanding of the biological differences by anatomic sites of presentation. Table Anatomical distribution and median overall survival of isolated myeloid sarcoma Table. Anatomical distribution and median overall survival of isolated myeloid sarcoma Figure Overall survival by sex and race in isolated myeloid sarcoma Figure. Overall survival by sex and race in isolated myeloid sarcoma Disclosures Al-Kali: Onconova Therapeutics, Inc.: Research Funding; Celgene: Research Funding.


Author(s):  
Chezi Ganzel ◽  
Ju-Whei Lee ◽  
Hugo Fernandez ◽  
Elisabeth Paietta ◽  
Selina Luger ◽  
...  

Central nervous system (CNS) involvement in newly diagnosed acute myeloid leukemia (AML) patients is rare and systematic data regarding outcome are scarce. This retrospective study summarized data from 11 consecutive ECOG-ACRIN clinical trials for newly diagnosed AML patients. 3240 patients with AML were analyzed and 36 (1.11%) were found to have CNS involvement at diagnosis. The incidence of CNS disease among the 5 studies with per protocol mandatory lumbar puncture (LP) was similar to the incidence among studies where LP was done at the discretion of the investigator (0.86% vs. 1.41%, p=0.18). There was no significant difference in the complete remission (CR) rate between patients with CNS involvement and those with other extramedullary disease (EMD) sites or those with no EMD (52.8% vs. 59.3-60%). The median overall survival (OS) of CNS-positive patients, other EMD or no EMD was 11.4, 11.3 and 12.7 months, respectively. There was no difference in OS between patients with CNS involvement and those with other EMD (HR 0.96, adjusted p=0.84) or no EMD (HR 1.19, adjusted p=0.44). In conclusion, the reported incidence of CNS involvement of newly diagnosed AML is low (1.1%), irrespective of whether an LP is mandatory or not. The presence of CNS disease at diagnosis does not appear, in and of itself, to portend for a poor prognosis for either achieving an initial CR or OS.


BMC Surgery ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
LingXiang Kong ◽  
Tao Lv ◽  
Li Jiang ◽  
Jian Yang ◽  
Jiayin Yang

Abstract Background Adult hemiliver transplantation (AHLT) is an important approach given the current shortage of donor livers. However, the suitability of AHLT versus adult whole liver transplantation (AWLT) for recipients with high Model for End-Stage Liver Disease (MELD) scores remains controversial. Methods We divided patients undergoing AHLT and AWLT into subgroups according to their MELD scores (≥ 30: AHLT, n = 35; AWLT, n = 88; and < 30: AHLT, n = 323; AWLT, n = 323). Patients were matched by demographic data and perioperative conditions according to propensity scores. A cut-off value of 30 for MELD scores was determined by comparing the overall survival data of 735 cases of nontumor liver transplantation. Results Among patients with an MELD score ≥ 30 and < 30, AHLT was found to be associated with increased warm ischemia time, operative time, hospitalization time, and intraoperative blood loss compared with AWLT (P < 0.05). In the MELD ≥ 30 group, although the 5-year survival rate was significantly higher for AWLT than for AHLT (P = 0.037), there was no significant difference between AWLT and AHLT in the MELD < 30 group (P = 0.832); however, we did not observe a significant increase in specific complications following AHLT among patients with a high MELD score (≥ 30). Among these patients, the incidence of complications classified as Clavien-Dindo grade III or above was significantly higher in patients undergoing AHLT than in those undergoing AWLT (25.7% vs. 11.4%, P = 0.047). For the MELD < 30 group, there was no significant difference in the incidence of complications classified as Clavien-Dindo grade III or above for patients undergoing AHLT or AWLT. Conclusion In patients with an MELD score < 30, AHLT can achieve rates of mortality and overall survival comparable to AWLT. In those with an MELD score ≥ 30, the prognosis and incidence of complications classified as Clavien-Dindo III or above are significantly worse for AHLT than for AWLT; therefore, we may need to be more cautious regarding the conclusion that patients with a high MELD score can safely undergo AHLT.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15173-e15173
Author(s):  
Tetsuya Kusumoto ◽  
Koji Ando ◽  
Satoshi Ida ◽  
Yasue Kimura ◽  
Hiroshi Saeki ◽  
...  

e15173 Background: S-1 monotherapy or S-1/CDDP have remained important as a standard chemotherapy regimen for patients with advanced gastric cancer (AGC), based on the randomized phase III trials. Although S-1/docetaxel has been reported highly active and well tolerated for AGC by many researchers, it could not show the superiority compared with S-1 monotherapy in the recent international randomized trial. We have also demonstrated that it might be effective for patients with Stage III AGC in both preoperative and postoperative adjuvant setting. The aim of this study was to evaluate efficacy, toxicity and validity of S-1/docetaxel retrospectively, compared with the standard regimens. Methods: We conducted a retrospective review of the data of 89 patients with AGC who received chemotherapy who were given S-1-containing regimens as the first line chemotherapy; 15 patients treated with S-1 monotherapy, 21 with S-1/CDDP, and 53 with S-1/docetaxel. The objective response, adverse event (AE), progression-free survival (PFS), and overall survival (OS) were compared between the three groups. Results: The overall response rates (ORRs) were obtained 6.7%, 38.1% and 30.2% for S-1 monotherapy, S-1/CDDP, and S-1/docetaxel, respectively. The incidence of AEs was more frequent in S-1 based combined treatments than in the S-1 monotherapy, however there was no significant difference in the severe AEs between each group. Survival data showed that the PFSs were 121 days, 199 days and 178 days, respectively, and there was the significant difference between S-1 monotherapy and S-1/docetaxel (p<0.05). The overall survival showed that the MSTs were not significantly different. The conversion rate to the subsequent treatments following S-1 monotherapy was higher than the other treatments. Conclusions: S-1/docetaxel was active and well tolerated for the patients with ARGC as the first line. Although the Japanese guideline for treatment of gastric cancer recommends S-1 monotherapy or S-1/CDDP as the standard regimens, docetaxel could be applied for patients with AGC in case of CDDP-resistant or –naïve patients.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8609-8609 ◽  
Author(s):  
Hari Prasad Ravipati ◽  
Jonathan L. Kaufman ◽  
Amelia A. Langston ◽  
Lawrence Boise ◽  
Christopher Flowers ◽  
...  

8609 Background: Plasma cell leukemia (PCL) is an aggressive plasma cell disorder that is associated with poor outcomes. Previous studies have shown improved survival with bortezomib-based regimens in this subset of patients undergoing stem cell transplant (SCT), but this may reflect referral bias. Current knowledge evaluating outcomes of PCL is limited in the era of novel agents. Methods: We analyzed the Surveillance, Epidemiology, and End Results (SEER) database from 18 registries for survival characteristics in PCL stratified by age, sex, race and the era of diagnosis. International Classification of Diseases for Oncology 3rd edition histology code 9733 was used to identify cases. Results: From 1973 to 2009, 74826 cases of myeloma and 479 cases of PCL were recorded. Survival data was available for 397 PCL patients. The median overall survival (OS) was 6 months (95% Confidence Interval (CI): 4.8 months – 7.2 months); and 1-year, 2-year, and 4-year OS rates were 34%, 20%, and 9% compared to corresponding myeloma survival rates of 66%, 52%, and 32%, respectively. Median overall survival differences were observed for women vs. men (7 months vs. 5 months, p=0.026); black vs. white patients (7 months vs. 5 months, p=0.01); and patients aged <60 years vs. ≥ 60 years (9 months vs. 4 months; P=0.01), respectively. In addition, patients diagnosed after 2005 had superior median OS compared with patients diagnosed prior to 2005 (7 months vs. 3 months; P=0.005). Conclusions: Black patients, women and patients aged <60 years have improved OS compared to white patients, males and patients aged ≥ 60 years. The survival benefit seen in patients diagnosed after 2005 may be attributed to the benefit conferred by access to new agents, but OS remains poor. Newer treatment approaches for managing PCL are clearly needed.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 147-147
Author(s):  
Rui Jin ◽  
Zhaohui Jin ◽  
Sean P. Cleary ◽  
David M. Nagorney ◽  
Rory L. Smoot ◽  
...  

147 Background: Colorectal cancer is one of the leading causes of cancer related deaths with liver being most common site of CRC metastasis. More than 50% of the CRC patients will develop metastatic liver lesion that eventually leads to death in about 70% of them. In this retrospective review we reviewed the outcome of pts who received neoadjuvant chemotherapy followed by resection of liver lesion for metastatic colorectal cancer. Methods: 304 pts who had preoperative chemotherapy were identified from 1045 metastatic colorectal cancer patients who had liver metastasectomy at Mayo Clinic between 1997 and 2018. A retrospective review was conducted by using data from electronic medical records. Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Results: There were 113 (37%) female and 191 (63%) male pts. Median age at primary disease diagnosis was 56.5 yrs. Two hundred forty-nine pts presented with stage IV metastatic colorectal cancer. Primary tumor locations were: 53 right-sided, 117 left-sided and 133 rectum. 152 (50%) pts had extrahepatic metastases. Two pts were found to be MSI-H, 113 MSS, 189 unknown. BRAF mutation was found in 6 patients. RAS mutation was present in 84 patients, with 124 unknown. Pts received chemotherapy for median of 2.82 months. Single agent fluoropyrimidine was administered in 38 (12%) pts and rest receiving chemotherapy doublet or triplet with fluropyrimidine plus oxaliplatin being most common regimen. The median overall survival from primary diagnosis for the entire group was 74.5 months. Median overall survival from liver metastasectomy was 60.0 months. In univariate analysis, metachronous disease, age < 60 yrs, and an absence of extrahepatic lesions led to statistically significant improvement of overall survival from primary diagnosis. Metachronous and extrahepatic lesions remained statistically significant in multivariate analysis. Conclusions: Neoadjuvant chemotherapy followed by liver metastasectomy is beneficial for highly-selected metastatic colorectal cancer pts. Compared to a historical control of 30-36 months, our patient population had a median overall survival of about 5 years from resection.


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