BRCA1-associated and sporadic ovarian carcinomas: outcomes of primary cytoreductive surgery or neoadjuvant chemotherapy

2019 ◽  
Vol 29 (4) ◽  
pp. 779-786 ◽  
Author(s):  
Tatyana Gorodnova ◽  
Anna Sokolenko ◽  
Valeria Ni ◽  
Alexandr Ivantsov ◽  
Khristina Kotiv ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Ovarian Carcinomas ◽  
Disease Free Interval ◽  
Primary Surgery ◽  
Free Interval ◽  
Mutation Carriers ◽  
Disease Free

ObjectiveTumors arising in BRCA1/2 mutation carriers are characterized by increased platinum sensitivity; however, it is unknown whether this feature should be considered while choosing between primary surgical versus systemic treatment. This study aimed to compare outcomes of ovarian cancer patients undergoing either primary surgery or interval cytoreduction based on BRCA1/2 status.MethodsThe study included consecutive ovarian cancer patients, who were treated at the N.N. Petrov Institute of Oncology (St Petersburg, Russia) from 2000 to 2013 and who underwent complete or optimal cytoreductive surgery. A comparison of disease outcomes was performed for the total group of ovarian cancer patients as well as for 69 BRCA1-mutated and 151 sporadic high-grade serous advanced-stage ovarian carcinomas. Frequency comparisons were performed by Chi-square test or Fisher exact test. Disease-free interval and overall survival were analyzed by Mann-Whitney U-test and Kaplan-Meier method. Hazard ratios were calculated by Cox regression analysis.ResultsThe analysis included 283 consecutive patients who underwent optimal cytoreduction (size of residual tumor <1 cm (n=156)) or complete tumor excision (n=127) on primary surgery (n=168) or after neoadjuvant chemotherapy (n=115). 84 patients carried germline mutation in BRCA1 (n=77) or BRCA2 (n=7) genes, while 199 ovarian cancer patients were classified as sporadic. High-grade serous ovarian cancer patients treated with neoadjuvant chemotherapy had a lower disease-free interval compared with those undergoing primary surgery followed by adjuvant therapy (7.8 vs 14.2 months, p<0.001). This difference was attributed mainly to sporadic cases (5.1 vs 12.2 months, p<0.001), while BRCA1-associated cancers had a similar disease-free interval regardless of the sequence of treatments (12.5 vs 15.8 months, p=0.53). When treated with neoadjuvant chemotherapy, BRCA1-mutated patients had improved overall survival as compared with sporadic cases (45.7 vs 25.3 months, p=0.007), while patients subjected to primary surgery showed similar overall survival irrespective of BRCA1 status (54.6 vs 53.9 months, p=0.56). A total of 29/61 (48%) BRCA1/2-associated patients relapsed as a single local tumor; this was lower in sporadic cancer patients (38/134 (28%); p=0.01).ConclusionIn BRCA1 mutation carriers, the oncologic outcomes are similar when comparing primary surgery versus neoadjuvant chemotherapy. In addition, BRCA1-mutation carriers often have a single site of disease when diagnosed with recurrent ovarian cancer.

Non-surgical Treatments for Lung Metastases in Patients with soft Tissue Sarcoma: Stereotactic Body Radiation Therapy (SBRT) and Radiofrequency Ablation (RFA)

2020 ◽  
Vol 16 ◽  
Author(s):  
Cecilia Tetta ◽  
Maria Carpenzano ◽  
Areej Tawfiq J Algargoush ◽  
Marwah Algargoosh ◽  
Francesco Londero ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Stereotactic Body Radiation Therapy ◽  
Lung Metastases ◽  
Disease Free Interval ◽  
Stereotactic Body Radiation ◽  
Free Interval ◽  
Disease Free

Background: Radio-frequency ablation (RFA) and Stereotactic Body Radiation Therapy (SBRT) are two emerging therapies for lung metastases. Introduction: We performed a literature review to evaluate outcomes and complications of these procedures in patients with lung metastases from soft tissue sarcoma (STS). Method: After selection, seven studies were included for each treatment encompassing a total of 424 patients: 218 in the SBRT group and 206 in the RFA group. Results: The mean age ranged from 47.9 to 64 years in the SBRT group and from 48 to 62.7 years in the RFA group. The most common histologic subtype was, in both groups, leiomyosarcoma. : In the SBRT group, median overall survival ranged from 25.2 to 69 months and median disease-free interval from 8.4 to 45 months. Two out of seven studies reported G3 and one G3 toxicity, respectively. In RFA patients, overall survival ranged from 15 to 50 months. The most frequent complication was pneumothorax. : Local control showed high percentage for both procedures. Conclusion: SBRT is recommended in patients unsuitable to surgery, in synchronous bilateral pulmonary metastases, in case of deep lesions and in patients receiving high-risk systemic therapies. RFA is indicated in case of a long disease-free interval, in oligometastatic disease, when only the lung is involved, in small size lesions far from large vessels. : Further large randomized studies are necessary to establish whether these treatments may also represent a reliable alternative to surgery.

Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside.

1994 ◽  
Vol 12 (5) ◽  
pp. 1036-1044 ◽  
Author(s):  
P O Livingston ◽  
G Y Wong ◽  
S Adluri ◽  
Y Tao ◽  
M Padavan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stage Iii ◽  
Disease Free Interval ◽  
Free Interval ◽  
Ajcc Stage ◽  
Melanoma Patients ◽  
Stage Iii Melanoma ◽  
Receive Treatment ◽  
To Receive ◽  
Disease Free

PURPOSE To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction. PATIENTS AND METHODS One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy). RESULTS GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance. CONCLUSION (1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.

scholarly journals The Significance of Metastasectomy in Patients with Metastatic Renal Cell Carcinoma in the Era of Targeted Therapy

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoteng Yu ◽  
Bing Wang ◽  
Xuesong Li ◽  
Gang Lin ◽  
Cuijian Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Targeted Therapy ◽  
Renal Cell ◽  
Complete Resection ◽  
Disease Free Interval ◽  
Free Interval ◽  
Metastatic Sites ◽  
Disease Free

Objective. To investigate the efficacy of surgery in the treatment of metastatic renal cell carcinoma (mRCC) and to identify prognostic factors. Methods. A single center retrospective study of 96 patients with mRCC from December 2004 to August 2013. Results. The median follow-up time was 45 months. Thirty-one (32.3%) of the patients received complete resection of metastatic sites, 11 (11.5%) of the patients underwent incomplete resection of metastatic sites, and 54 (56.3%) of the patients received no surgery. In the univariate Kaplan-Meier analysis, the median overall survival times of the three groups were 52 months, 16 months, and 22 months, respectively (p<0.001). The difference in the overall survival time was statistically significant between complete resection and no surgery groups (HR = 0.43, p=0.009), while there was no significant difference between the incomplete metastasectomy and no surgery groups (HR = 1.80, p=0.102). According to the multivariate Cox regression analysis, complete metastasectomy (HR = 0.49, p=0.033), T stage > 3 (HR = 1.88, p=0.015), disease free interval <12 months (HR = 2.34, p=0.003), and multiorgan involvement (HR = 2.00, p=0.011) were significant prognostic factors. Conclusion. In the era of targeted therapy, complete metastasectomy can improve overall survival. Complete metastasectomy, T stage > 3, disease free interval <12 months, and multiorgan involvement are independent prognostic factors.

804 Does Neoadjuvant Chemotherapy with FOLFOX- or FOLFIRI Improve the Disease-Free Interval or Survival of Patients with Colorectal Metastases?

2009 ◽  
Vol 136 (5) ◽  
pp. A-878
Author(s):  
Sarah Y. Boostrom ◽  
David Nagorney ◽  
John H. Donohue ◽  
Florencia G. Que ◽  
Michael L. Kendrick ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Colorectal Metastases ◽  
Disease Free Interval ◽  
Free Interval ◽  
Disease Free

5T4 oncofetal antigen expression in ovarian carcinoma

1995 ◽  
Vol 5 (4) ◽  
pp. 269-274 ◽  
Author(s):  
E. Wrigley ◽  
A. T. Mcgown ◽  
J. Rennison ◽  
R. Swindell ◽  
D. Crowther ◽  
...  
Keyword(s):  
Antigen Expression ◽  
Figo Stage ◽  
Ovarian Carcinomas ◽  
Disease Free Interval ◽  
Free Interval ◽  
Adenocarcinoma Cells ◽  
Stromal Tissue ◽  
Poorly Differentiated ◽  
Low Levels ◽  
Disease Free

5T4 oncofetal antigen is defined by a monoclonal antibody raised against human placental trophoblast, and recognizes a 72 kD glycoprotein expressed in many different carcinomas but detected only at low levels in some normal epithelia. Analysis of the patterns of expression of 5T4 oncofetal antigen in colorectal carcinomas has indicated a significant association between the presence of the antigen in tumor cells and metastatic spread. The 5T4 antigen expression of 72 epithelial ovarian carcinomas has been investigated by immunohistochemistry; 71% of the carcinomas demonstrated positive 5T4 immunoreactivity in adenocarcinoma cells and/or associated stromal tissue. In order to assess any relationship to prognosis, the 5T4 phenotypes were analyzed with respect to various clinicopathologic features of the tumors and the clinical outcome of the patients assessed by survival and disease-free interval. There was a significant correlation between 5T4 expression and more advanced stage of disease (FIGO stages III and IV) (P< 0.001) and with poorly differentiated tumors (P= 0.036) compared to well or moderately differentiated tumors. Patients with tumors expressing 5T4 were less likely to respond well to adjuvant therapy (P= 0.030) and had a significantly worse outlook in terms of survival (P= 0.033) and disease-free interval (P= 0.033). This significance was not demonstrated as acting independently of FIGO stage and tumor differentiation.

scholarly journals Urokinase plasminogen activator: a prognostic marker in breast cancer including patients with axillary node-negative disease

1998 ◽  
Vol 44 (6) ◽  
pp. 1177-1183 ◽  
Author(s):  
Michael J Duffy ◽  
Catherine Duggan ◽  
Hugh E Mulcahy ◽  
Enda W McDermott ◽  
Niall J O’Higgins
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Plasminogen Activator ◽  
Prognostic Marker ◽  
Urokinase Plasminogen Activator ◽  
Lymph Node Status ◽  
Disease Free Interval ◽  
Node Negative ◽  
Free Interval ◽  
Disease Free

Abstract Urokinase plasminogen activator (uPA) is a serine protease causally involved in cancer invasion and metastasis. In this study, high concentrations of uPA in primary breast cancers were independently associated with both a shortened disease-free interval and overall survival. For the disease-free interval as endpoint, uPA was a stronger indicator of outcome than lymph node status, whereas for overall survival, nodal status was stronger than uPA. In patients without metastasis to axillary nodes, uPA was also an independent prognostic marker, using both the disease-free interval and overall survival as end points. In contrast to uPA, neither tumor size nor estrogen receptor status was prognostic in the node-negative patients. Measurement of uPA concentrations might thus be of value in selecting the more aggressive subpopulation of node-negative breast cancer patients that could benefit from adjuvant therapy.

scholarly journals The Capacity of the Ovarian Cancer Tumor Microenvironment to Integrate Inflammation Signaling Conveys a Shorter Disease-free Interval

2020 ◽  
Vol 26 (23) ◽  
pp. 6362-6373 ◽  
Author(s):  
Kimberly R. Jordan ◽  
Matthew J. Sikora ◽  
Jill E. Slansky ◽  
Angela Minic ◽  
Jennifer K. Richer ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Microenvironment ◽  
Disease Free Interval ◽  
Free Interval ◽  
Cancer Tumor ◽  
Disease Free

Maintenance treatment in relapsed canine lymphoma after a short L-CHOP protocol

2021 ◽  
Vol 49 (03) ◽  
pp. 185-194
Author(s):  
Karin Troedson ◽  
Nataliia Ignatenko ◽  
Csilla Fejos ◽  
Yury Zablotski ◽  
Johannes Hirschberger
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Adverse Events ◽  
Survival Time ◽  
Maintenance Treatment ◽  
Canine Lymphoma ◽  
Disease Free Interval ◽  
Overall Survival Time ◽  
Free Interval ◽  
Disease Free

Abstract Objective A number of different rescue protocols for relapsed canine multicentric large-cell lymphoma have been described. The aim of this pilot study was to evaluate the efficacy of a maintenance treatment in dogs that experienced a second complete remission after a short L-CHOP-rescue protocol. Material and methods Included in the study were dogs experiencing the first lymphoma relapse during a treatment-free period which were treated with a short L-CHOP protocol, achieved a complete remission and were afterwards treated with a continuous maintenance phase (MP) protocol. The L-CHOP protocol consisted of weekly treatments, with at least 3 additional treatments following complete remission. Thereafter the MP protocol with 2-week treatment intervals was conducted. It consisted of alternating oral home administration of different alkylating agents and one intravenously administered cytotoxic agent of a different mechanism of action. The dogs were presented either every 4 or 6 weeks for intravenous treatment and at this time a complete blood count was performed. The durations of the first remission, disease-free interval and overall survival time were evaluated. Results A total of 20 dogs were included in the study. A median of 7 weekly applications were given before the treatment was switched to the MP protocol. During MP, 14 dogs were treated intravenously every 6 weeks and 6 dogs every 4 weeks. Haematological adverse events were mainly mild. During the L-CHOP-protocol, one septic event occurred, and 2 dogs were hospitalized due to gastrointestinal adverse events. No patient required hospitalization during the MP. Fifteen dogs completed at least one cycle in the MP and a median of 8.5 chemotherapeutic treatments were administered. The median disease-free interval was 264 days and the median overall survival time was 737 days. Conclusion and clinical relevance The protocol was generally well tolerated. Since 5 patients showed disease progression during the first cycle of the MP, dogs should ideally be evaluated for minimal residual disease before being switched to the MP. The case number in the presented study was low and the treatment relatively heterogeneous. Therefore, more dogs have to be treated with the proposed protocol before general recommendations can be made.

Second Autologous Stem Cell Transplant (ASCT) as Salvage Therapy in Patients with Relapsed Multiple Myeloma: Improved Outcomes in Patients with Longer Disease Free Interval after First ASCT.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 946-946 ◽  
Author(s):  
Joseph R. Mikhael ◽  
Sahar Zadeh ◽  
Sara Samiee ◽  
Keith Stewart ◽  
Christine Chen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Salvage Therapy ◽  
Median Overall Survival ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Disease Free Interval ◽  
Free Survival ◽  
Free Interval ◽  
Disease Free

Abstract Background: Single autologous stem cell transplant (ASCT) is considered the standard of care for younger multiple myeloma (MM) patients (pts). However, it is not curative and virtually all patients will ultimately relapse. As more options, such as biological therapy, are available to treat relapsed disease, the role of a second ASCT as salvage therapy is unclear. Method: Retrospective review of all MM pts who received a 2nd ASCT as salvage therapy at Princess Margaret Hospital. Results: Between February 1997 and June 2007, 61 MM pts received a second ASCT for relapsed MM at our institution. Median age was 56 yrs (range 35–71) at second transplant. 37 pts (61%) were male. Immunoglobulin subtype included IgG (36), IgA (14), light chain (6), nonsecretory (3), IgM(1) and IgD (1). Transplant conditioning regimen for first transplant was high dose melphalan (MEL) 140–200 mg/m2 in 51, MEL/etoposide(E)/TBI in 4, and MELl/TBI in 2. 2nd ASCT conditioning consisted of MEL + TBI +/− E in 2, MEL alone in 58 and Busulfan/Cyclophosphomide in 1. The median time from diagnosis to first transplant was 9.7 months (2.0–74.2). The median time to relapse after the first transplant was 32.6 months (9.7–85.6), with a median interval between transplants of 45.1 months (19.7– 115). Two transplant-related deaths occurred (3%). Response to first transplant was 4 CR (8%), 34 PR (68%), 2 MR (4%) and 10 SD (20%). Nineteen pts went on to maintenance therapy between transplants. Response to second transplant was 4 CR (8%), 41 PR (80%), 5 SD (10%) and 1 PD (2%). Median progression-free survival (PFS) was 15.8 months (0–63.8) while median overall survival (OS) was 4.2 years (0–7.0) after 2nd ASCT. The relationship between progression-free interval after 1st ASCT and the outcome of the 2nd ASCT is summarized Table 1. Patients can be stratified into two groups, those with a disease free interval of less than or greater than 24 months. The use of maintenance therapy did not differ between the two groups, 6 (40%) in patients with PFS ≤24 months and 13 (28%) in patients with PFS >24 months. Conclusions: 2nd ASCT is a feasible and safe salvage therapy in patients with relapsed MM. 2nd ASCT is effective in providing a median progression free survival of 1.25 years and median overall survival of 4.2 years after 2nd ASCT - results that compare favourably with other salvage approaches. Patients with a longer disease free interval after 1st ASCT experience a better progression free survival and overall survival after 2nd ASCT. It is reasonable, therefore, to consider a 2nd ASCT if the time to progression is greater than 2 years after first ASCT. Outcomes Based on Time to Progression Post 1st ASCT PFS post 1st ASCT # of pts median PFS post 2nd ASCT PFS post 2nd ASCT1 Median OS post 2nd ASCT OS post 2nd ASCT2 1 p< 0.005, 2 p< 0.05 ≤24 months 15 12.7 months 1 year: 46% 3.5 years 1 year: 85% 2 year: 11% 2 years: 76% 3 years 0% 3 years: 63% 4 years: 31% > 24 months 46 19.8 months 1 year: 74% 5.9 years 1 year: 91% 2 year: 45% 2 years: 82% 3 year: 31% 3 years: 65% 4 years: 55%

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