Factors influencing prognosis in node-negative breast carcinoma: analysis of 767 T1N0M0/T2N0M0 patients with long-term follow-up.

1993 ◽  
Vol 11 (11) ◽  
pp. 2090-2100 ◽  
Author(s):  
P P Rosen ◽  
S Groshen ◽  
D W Kinne ◽  
L Norton

PURPOSE This study was undertaken to define prognostically favorable and unfavorable subgroups of node-negative breast carcinoma patients by employing conventional pathologic data. PATIENTS AND METHODS Seven hundred sixty-seven women with T1N0M0/T2N0M0 breast carcinoma treated consecutively from 1964 through 1970 by modified or radical mastectomy without systemic adjuvant therapy were analyzed at a median follow-up duration of 18 years. RESULTS Size and histologic type of the carcinoma were crucial discriminants of prognosis. We defined a prognostically favorable group of 219 patients (29%) with infiltrating duct or lobular carcinoma < or = 1.0 cm in diameter or special tumor types < or = 3.0 cm. This group had a relapse-free survival rate of 91% at 10 years and 87% at 20 years. The less favorable group (548 patients, 71%) with infiltrating duct or lobular carcinoma greater than 1.0 cm and special tumor types greater than 3.0 cm had relapse-free survival rates of 73% and 68% at 10 and 20 years, respectively. The frequency of nonmammary malignant neoplasms (NMMN) was similar to that of contralateral carcinoma. Deaths due to NMMN were seven times more frequent than deaths due to contralateral carcinoma. CONCLUSION Nearly 30% of these node-negative patients, identified on the basis of tumor size and type, had an extremely favorable prognosis. There is insufficient evidence to warrant the routine use of adjuvant therapy in this group unless new forms of treatment prove to be less toxic and/or more effective in enhancing relapse-free survival. Early detection of NMMN should be an important part of the follow-up of node-negative breast carcinoma patients.

2002 ◽  
Vol 20 (8) ◽  
pp. 2067-2075 ◽  
Author(s):  
Jeffrey A. Sosman ◽  
Joseph M. Unger ◽  
P.-Y. Liu ◽  
Lawrence E. Flaherty ◽  
Min S. Park ◽  
...  

PURPOSE: An association between expression of ≥ two of five HLA class I antigens (HLA-A2, HLA-A28, HLA-B44, HLA-B45, and HLA-C3; collectively called M5) and response to an allogeneic melanoma vaccine (Melacine; Corixa Corporation, Seattle, WA) has been described in stage IV melanoma. This study investigated whether class I antigen expression impacted relapse-free survival (RFS) after adjuvant therapy with this vaccine. PATIENTS AND METHODS: We performed class I (HLA-A, HLA-B, and HLA-C) serotyping on patients enrolled onto Southwest Oncology Group Trial 9035, a randomized, observation-controlled, phase III trial of adjuvant Melacine. All patients had clinically node-negative cutaneous melanoma (1.5 to 4.0 mm). Interactions between treatment and class I antigen expression were tested. Analyses involved all serotyped patients and were adjusted for tumor thickness, method of nodal staging, sex, ulceration, and primary tumor site. RESULTS: HLA typing was performed on 553 (80%) of the 689 enrolled patients (294 vaccinated and 259 observed). Expression of ≥ two M5 antigens was associated with a superior vaccine treatment effect. Among patients who matched ≥ two of the M5, the 97 vaccine-treated patients had improved RFS compared with the 78 observation patients (5-year relapse-free survival, 83% v 59%; P = .0002). The major components of this effect were contributed by HLA-A2 and HLA-C3. Among those who were HLA-A2–positive and/or HLA-C3–positive, the 5-year RFS for vaccinated patients was 77%, compared with 64% for observation (P = .004). There was no impact of HLA-A2 and/or HLA-C3 expression among observation patients. CONCLUSION: This prospective analysis indicates a highly significant benefit of adjuvant therapy with Melacine among patients expressing ≥ two of the M5 class I antigens, validating a prior observation in stage IV disease. HLA-A2 and HLA-C3 contributed most to this effect. Processed melanoma peptides found in Melacine may be presented by HLA-A2 and HLA-C3 and play a role in preventing relapse in vaccinated patients.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4004-4004 ◽  
Author(s):  
Robert Glynne-Jones ◽  
Roger James ◽  
Helen Meadows ◽  
Rubina Begum ◽  
David Cunningham ◽  
...  

4004 Background: In the ACT I trial, relapse-free survival was improved with CRT compared to RT alone, but the CR rate at 6 weeks was similar (39% CRT, 30% RT alone; p=0.08). Most studies assessed CR between 6 and 12 weeks following completion of CRT. We investigated the association between observation of CR at 3 different time-points and progression-free and overall survival (PFS, OS), to determine the optimal time to assess this early endpoint. Methods: ACT II recruited 940 pts between 2001 and 2008. It compared, in a factorial design, CisP versus MMC when combined with 5-FU CRT, and two cycles of maintenance chemotherapy versus no maintenance. CR (complete absence of tumour and node negative) was assessed by rectal exam or imaging at 11, 18 and mandated CT at 26 weeks after the start of CRT. Median follow-up was 5 years. Pts were excluded from analysis if assessment was not done/ missing at one or more time points (n=245). Data from 695 pts were analysed. Results: Pt characteristics (all 940) median age 58 years; tumour site – canal (84%), margin (14%); stage T1-T2 (52%), T3-T4 (46%); N+ (32%), N0 (62%). CisP did not improve OS (HR: 0.96, p=0.89) or PFS (HR: 0.85, p=0.43) compared to MMC. This is consistent with the lack of an absolute difference at 18 and 26 weeks, but not at 11 weeks (where a difference was found). CR patients (compared to not-CR) had a significantly lower risk of progression/death. The association between these outcomes and response was strongest at 26 weeks. 202/695 (29%) pts not in CR at 11 weeks were CR at 26 weeks. Conclusions: 29% of pts not in CR at 11 weeks achieved CR at 26 weeks. Early surgical salvage would not have been appropriate for these pts. We recommend assessment at 26 weeks in future trials. [Table: see text]


1991 ◽  
Vol 9 (9) ◽  
pp. 1650-1661 ◽  
Author(s):  
P P Rosen ◽  
S Groshen ◽  
D W Kinne

In a study of prognosis in node-negative breast carcinoma, we investigated 293 T2N0M0 patients treated by mastectomy and axillary dissection with a median follow-up of 19.8 years. The probability of surviving 20 years considering all causes of death was 41.3% +/- 3.0%. Recurrence-free survival (Kaplan-Meier estimate) was 68.6% +/- 3% at 10 years and 63.2% +/- 3.1% at 20 years. The estimated probability of cure determined by the method of Brinkley and Haybittle was 63% (95% confidence interval [Cl], 55% to 72%). Prognosis was related to primary tumor size with the best separation (P = .06) when tumors from 2.1 to 3.0 cm (33% chance of recurrence at 20 years) and from 3.1 to 5.0 cm (44% chance of recurrence at 20 years) were compared. The histologic tumor type was prognostically important. Recurrence at 20 years was not significantly different for patients with invasive duct (34%) and lobular (42%) carcinoma. Women with special types (medullary, mucinous, papillary, etc) of carcinoma had a 25% chance of recurrence. Subsequent contralateral breast carcinoma was diagnosed in 29 patients, and four of these were fatal, accounting for only 4.6% of breast carcinoma deaths. Thirty-two patients (10.9%) developed a nonmammary malignant neoplasm (NMMN) after the ipsilateral breast carcinoma, and 69% of these lesions were fatal. Although the chances of recurrence at 20 years related to tumor size and type did not differ statistically in the series, there were trends that suggest that T2N0M0 patients can be stratified into recurrence risk groups based on tumor size and histologic type. These factors should be taken into consideration in the design and analysis of clinical adjuvant therapy trials. Measures for the early detection of common NMMNs should be included in the routine follow-up of T2N0M0 breast carcinoma patients.


1989 ◽  
Vol 7 (3) ◽  
pp. 355-366 ◽  
Author(s):  
P R Rosen ◽  
S Groshen ◽  
P E Saigo ◽  
D W Kinne ◽  
S Hellman

This study was undertaken to investigate the long-term survival and the probability of "cure" in a group of 644 patients treated by mastectomy for T1 breast carcinoma. After a median follow-up of 18.2 years, 23% were dead of recurrent breast carcinoma, 3% were alive with recurrent disease, and 74% had not experienced a recurrence. The probability of recurrence was directly related to the initial extent of the disease. Overall, 16% of recurrences and 25% of deaths due to disease occurred in the second decade of follow-up. The proportion of recurrences detected in the second decade was inversely related to the stage of the primary tumor at diagnosis. When stratified by tumor size, T1N0M0 patients with tumors 1.0 cm or less in diameter had a significantly better 20-year recurrence-free survival (86%) than did T1N0M0 patients with tumors 1.1 to 2.0 cm (69%). When observed and expected survival curves were compared by the method of Brinkley and Haybittle, it appeared that 80% of T1N0M0 patients with tumors 1 cm or less might be cured at 20 years, whereas for those in the 1.1- to 2-cm group, the proportion cured was indeterminate, but might be as high as 70%. A potentially cured group could not be identified among T1N1M0 patients, but an estimated 52% of these patients did not have a recurrence within the nearly 20-year follow-up period. These data are important when one considers the proper role of adjuvant therapy for stage I disease. Patients with tumors larger than 1 cm and those with axillary lymph node metastases may have an improved recurrence-free survival as a result of systemic adjuvant treatment, while women in the T1N0M0 group with an especially favorable recurrence-free survival, particularly those with tumors 1 cm in diameter or smaller, might be spared adjuvant therapy.


Author(s):  
Alexander C.J. van Akkooi ◽  
Michael B. Atkins ◽  
Sanjiv S. Agarwala ◽  
Paul Lorigan

Wide local excision is considered routine therapy after initial diagnosis of primary melanoma to reduce local recurrences, but it does not impact survival. Sentinel node staging is recommended for melanomas of intermediate thickness, but it has also not demonstrated any indisputable therapeutic effect on survival. The prognostic value of sentinel node staging has been long established and is therefore considered routine, especially in light of the eligibility criteria for adjuvant therapy (trials). Whether completion lymph node dissection after a positive sentinel node biopsy improves survival is the question of current trials. The MSLT-2 study is best powered to show a potential benefit, but it has not yet reported any data. Another study, the German DECOG study, presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting did not show any benefit but is criticized for the underpowered design and insufficient follow-up. There is no consensus on the use of adjuvant interferon in melanoma. This topic has been the focus of many studies with different regimens (low-, intermediate-, or high-dose and/or short- or long-term treatment). Adjuvant interferon has been shown to improve relapse-free survival but failed to improve overall survival. More recently, adjuvant ipilimumab has also demonstrated an improved relapse-free survival. Overall survival data have not yet been reported due to insufficient follow-up. Currently, studies are ongoing to analyze the use of adjuvant anti–PD-1 and molecular targeted therapies (vemurafenib, dabrafenib, and trametinib). In the absence of unambiguously positive approved agents, clinical trial participation remains a priority. This could change in the near future.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1552.3-1552
Author(s):  
A. Mekinian ◽  
D. Saadoun ◽  
J. C. N. F. [email protected] ◽  
I. Q. M. F. [email protected] ◽  
P. Jégo ◽  
...  

Objectives:To assess long term efficacy of tocilizumab in treatment-naive patients with Takayasu arteritis (TAK).Methods:In this multicenter, prospective, open-labelled trial, we aim to evaluate the benefit of adding tocilizumab to steroids in treatment-naïve patients with TAK, on discontinuation of steroids after 6 months of tocilizumab treatment, and to assess relapse-free survival following tocilizumab discontinuation.Results:Thirteen patients with TAK were included, with a median age of 32 years [19-45] and 12 (92%) females. Six (54%) patients met the primary end-point. Among 11 (85%) patients which achieved remission at 6 months, 6 (54%) have reached primary endpoint.. Among the 5 remaining patients which continued steroids, 3 had a prednisone-equivalent dosage < 5mg/day. A significant decrease of disease activity was observed after 6 months of tocilizumab therapy: decrease of median NIH scale (3 [3-4] at baseline, versus 1 [0-2] after 6 months; p <0.001), ITAS-2010 score (5 [2-7] versus 3 [0-8]; p = 0.002), and ITAS-A score (7 [4-10] versus 4 [1-15]; p = 0.0001)]. All patients discontinued tocilizumab after 7 infusions, and no other immunosuppressive drugs was introduced, except for 1 patient which received methotrexate. After 9 and 12 months, respectively 7 (54%) and 6 (50%) patients achieved remission with less than 7.5 mg/day of prednisone, and 9 (69%) and 9 (75%) with doses <10 mg/day. During the 12 months follow-up after tocilizumab discontinuation, a relapse occurred among 5 patients (45%) out of 11 in which achieved remission after 6 months of tocilizumab.No severe AEs were considered related to study treatment and none required tocilizumab interruption or dose reduction. No deaths have occurred during the study period.Conclusion:Tocilizumab seems an effective steroid sparing therapy in TAK but its effect appears to be suspensive.Disclosure of Interests:Arsene Mekinian: None declared, david Saadoun: None declared, [email protected] [email protected]: None declared, [email protected] [email protected]: None declared, Patrick Jégo: None declared, [email protected] [email protected]: None declared, wxv wxv: None declared, Jacques-Eric Gottenberg Grant/research support from: BMS, Pfizer, Consultant of: BMS, Sanofi-Genzyme, UCB, Speakers bureau: Abbvie, Eli Lilly and Co., Roche, Sanofi-Genzyme, UCB, Mathieu Vautier: None declared, [email protected]>; [email protected]>;: None declared, Patrice cacoub: None declared, olivier fain: None declared


Author(s):  
Bei-Bei Xiao ◽  
Qiu-Yan Chen ◽  
Xue-Song Sun ◽  
Ji-Bin Li ◽  
Dong-hua Luo ◽  
...  

Abstract Objectives The value of using PET/CT for staging of stage I–II NPC remains unclear. Hence, we aimed to investigate the survival benefit of PET/CT for staging of early-stage NPC before radical therapy. Methods A total of 1003 patients with pathologically confirmed NPC of stages I–II were consecutively enrolled. Among them, 218 patients underwent both PET/CT and conventional workup ([CWU], head-and-neck MRI, chest radiograph, liver ultrasound, bone scintigraphy) before treatment. The remaining 785 patients only underwent CWU. The standard of truth (SOT) for lymph node metastasis was defined by the change of size according to follow-up MRI. The diagnostic efficacies were compared in 218 patients who underwent both PET/CT and CWU. After covariate adjustment using propensity scoring, a cohort of 872 patients (218 with and 654 without pre-treatment PET/CT) was included. The primary outcome was overall survival based on intention to treat. Results Retropharyngeal lymph nodes were metastatic based on follow-up MRI in 79 cases. PET/CT was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions (72.2% [62.3–82.1] vs. 91.1% [84.8–97.4], p = 0.004). Neck lymph nodes were metastatic in 89 cases and PET/CT was more sensitive than MRI (96.6% [92.8–100.0] vs. 76.4% [67.6–85.2], p < 0.001). In the survival analyses, there was no association between pre-treatment PET/CT use and improved overall survival, progression-free survival, local relapse-free survival, regional relapse-free survival, and distant metastasis-free survival. Conclusions This study showed PET/CT is of little value for staging of stage I–II NPC patients at initial imaging. Key Points • PET/CT was more sensitive than MRI in detecting neck lymph node lesions whereas it was significantly less sensitive than MRI in detecting retropharyngeal lymph node lesions. • No association existed between pre-treatment PET/CT use and improved survival in stage I–II NPC patients.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3935-3935
Author(s):  
Shanee Chung ◽  
Jennifer White ◽  
Cynthia L. Toze ◽  
Heather J. Sutherland ◽  
David Sanford ◽  
...  

Abstract Introduction: Patients newly diagnosed with classic Hodgkin lymphoma (CHL) have over 80% chance of remission with first-line chemotherapy, such as ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) regime. However, 10-40% of patients relapse eventually and require salvage therapy. High-dose therapy with autologous stem cell transplantation (ASCT) remains the standard of care for patients with relapsed or refractory CHL, offering a cure rate of around 50%. This may be further improved to around 60% with post-transplant consolidation with brentuximab vedotin (BV). Post-SCT BV consolidation has been offered to all patients, regardless of the risk group, in British Columbia since late 2015. We set out to review the ASCT outcome in CHL patients in the recent decade at our institution. Methods: All adult patients who received ASCT for relapsed or refractory CHL between July 2011 and June 2020 were included in this retrospective analysis. Information pertaining to their demographics, disease characteristics, treatment history, transplant details, clinical outcomes and post-relapse therapy was obtained by review of electronic data. The data cut-off date was June 28, 2021. Survival outcomes were censored at the last known clinic visit for patients without relapse or death during follow up. Survival analysis was performed using Kaplan-Meier survival function and log-rank test. Pearson's chi-square test and ANOVA were used for comparison between cohorts. The statistical program used was Stata® version 16.1 (Texas, USA). Results: 114 patients underwent ASCT for relapsed/refractory CHL. Bulky disease and extranodal involvement were seen in 11% and 40% respectively at relapse. Looking at the 'high risk criteria' as defined in the AETHERA trial: 45/114 (40%) patients had primary refractory CHL, 21/114 (18%) had relapsed within 12 months of completing the front-line chemotherapy and 15/114 (13%) had relapsed beyond one year of completing initial treatment but with an extranodal disease. The most commonly used salvage chemotherapy regime was GDP (gemcitabine, dexamethasone, cisplatin; 111/114; 97%). 10/114 (9%) patients received BV after failing salvage chemotherapy pre-SCT. The median number of lines of therapy pre-SCT was two (range 2-5). 94/108 (98%) had a chemosensitive disease with 35/108 (32%) achieving complete remission. 6/108 (6%) patients had a progressive disease at the time of SCT. For the transplant, all patients had a peripheral blood stem cell source and the conditioning regime was either Carmustine/Etoposide/Cytarabine/Melphalan (76%) or Etoposide/Melphalan (24%). After median follow up of 62.2 months, 50/114 (44%) patients relapsed with median relapse-free survival of 20.2 months (range 0.9 - 113.5) and 16/114 (14%) died. The direct cause of death was lymphoma progression in all but three patients (PJP pneumonia, pulmonary fibrosis, traumatic subdural hematoma). Whereas only 4/51 (8%) patients (2 without relapse) received post-SCT BV consolidation via a compassionate access program between July 2011 and October 2015 (cohort 1), 45/63 (71%) patients (33 in remission) received routine BV consolidation between November 2015 and June 2020 (cohort 2). In cohort 2, 44% had primary refractory CHL compared to 33% in cohort 1 but the number of 'low risk' patients was similar at 29% (Table 1). The most common reason for no post-SCT BV consolidation in cohort 2 was patient refusal (7/18; 40%). Other causes included BV pre-SCT, early disease progression and patient comorbidities. Only 9/42 (21%) patients with available data in cohort 2 completed the planned 16 cycles of BV consolidation. The median number of cycles was 10.5 (range 1-16). The most common reasons for early termination of BV consolidation were peripheral neuropathy (22/33; 67%) and disease progression (9/33; 27%). There was no statistically significant difference in PFS or OS demonstrated between the two cohorts (Graphs 1, 2). Conclusion: After median follow up of 5 years, 86% of patients remain alive and 56% are alive in remission. In British Columbia, post-SCT BV consolidation has been widely adopted with over 70% of patients receiving at least one cycle since late 2015. Successful completion of post-SCT BV consolidation is, however, limited by a high rate of treatment-limiting peripheral neuropathy. Relapse-free survival benefit of routine post-SCT BV consolidation is not demonstrated in this single-centre cohort. Figure 1 Figure 1. Disclosures White: Novartis: Honoraria. Sutherland: Janssen: Consultancy, Research Funding; GSK: Research Funding; Karyopharm: Research Funding; Celgene: Consultancy; Amgen: Consultancy. Sanford: Abbvie: Membership on an entity's Board of Directors or advisory committees; Stellar: Membership on an entity's Board of Directors or advisory committees. Abou Mourad: Amgen: Consultancy; Paladin: Consultancy; Pfizer: Consultancy. Song: Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Honoraria; Kite, a Gilead Company: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria.


1995 ◽  
Vol 13 (11) ◽  
pp. 2712-2721 ◽  
Author(s):  
M R Sertoli ◽  
P Bruzzi ◽  
P Pronzato ◽  
P Queirolo ◽  
D Amoroso ◽  
...  

PURPOSE The aim of this multicentric randomized trial was to determine whether reducing the interval between surgery and chemotherapy improves the outcome of breast cancer patients. PATIENTS AND METHODS Between June 1985 and July 1992, 600 breast cancer patients, clinical stages T1-3A,N0-2,M0 were randomly assigned to a perioperative cycle (PC) of cyclophosphamide 600 mg/m2, epidoxorubicin 60 mg/m2, and fluorouracil 600 mg/m2 (CEF). Node-negative (N-) patients did not receive any further treatment. Node positive (N+) patients received 11 cycles if previously given PC, or 12 cycles of CEF alternated with cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 (CMF). In addition, N+ patients received concomitant or sequential 5-year tamoxifen therapy. RESULTS At a median follow-up duration of 5.7 years, no significant difference in survival (88% v 84%, P = .3) between the two treatment arms was seen. However, a difference of borderline significance in relapse-free survival (RFS; 76% v 70%, P = .053) was evident. A significant survival advantage for the PC arm was detected only in the estrogen receptor-negative (ER-) patients (P = .003). RFS was significantly improved in N- patients, postmenopausal patients, and ER- patients. Multivariate analyses show that pathologic tumor size, nodal status, receptor status, and treatment (only in ER- patients) are significantly correlated with survival and RFS. PC toxicity did not influence wound healing. CONCLUSION This study provides preliminary evidence that PC positively affects relapse rate and survival in some subgroups, namely, ER- patients.


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