scholarly journals No Impact of NRAS Mutation on Features of Primary and Metastatic Melanoma or on Outcomes of Checkpoint Inhibitor Immunotherapy: An Italian Melanoma Intergroup (IMI) Study

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 475
Author(s):  
Michele Guida ◽  
Nicola Bartolomeo ◽  
Pietro Quaglino ◽  
Gabriele Madonna ◽  
Jacopo Pigozzo ◽  
...  

Aims: It is debated whether the NRAS-mutant melanoma is more aggressive than NRAS wildtype. It is equally controversial whether NRAS-mutant metastatic melanoma (MM) is more responsive to checkpoint inhibitor immunotherapy (CII). 331 patients treated with CII as first-line were retrospectively recruited: 162 NRAS-mutant/BRAF wild-type (mut/wt) and 169 wt/wt. We compared the two cohorts regarding the characteristics of primary and metastatic disease, disease-free interval (DFI) and outcome to CII. No substantial differences were observed between the two groups at melanoma onset, except for a more frequent ulceration in the wt/wt group (p = 0.03). Also, the DFI was very similar in the two cohorts. In advanced disease, we only found lung and brain progression more frequent in the wt/wt group. Regarding the outcomes to CII, no significant differences were reported in overall response rate (ORR), disease control rate (DCR), progression free survival (PFS) or overall survival (OS) (42% versus 37%, 60% versus 59%, 12 (95% CI, 7–18) versus 9 months (95% CI, 6–16) and 32 (95% CI, 23–49) versus 27 months (95% CI, 16–35), respectively). Irrespectively of mutational status, a longer OS was significantly associated with normal LDH, <3 metastatic sites, lower white blood cell and platelet count, lower neutrophil-to-lymphocyte (N/L) ratio. Our data do not show increased aggressiveness and higher responsiveness to CII in NRAS-mutant MM.

2014 ◽  
Vol 128 (11) ◽  
pp. 996-1002 ◽  
Author(s):  
S Mallick ◽  
A K Gandhi ◽  
N P Joshi ◽  
S Pandit ◽  
S Bhasker ◽  
...  

AbstractObjective:To explore the treatment outcomes of patients treated with re-irradiation for recurrent or second primary head and neck cancer.Method:An analysis was performed of 79 head and neck cancer patients who underwent re-irradiation for second primaries or recurrent disease from January 1999 to December 2011.Results:Median time from previous radiation to re-irradiation for second primary or recurrence was 53.6 months (range, 2.7–454.7 months). Median age at diagnosis of first primary was 54 years. Median re-irradiation dose was 45 Gy (range, 45–60 Gy). Acute grade 3 or worse toxicity was seen in 30 per cent of patients. Median progression-free survival for recurrent disease was 15.0 months (95 per cent confidence interval, 8.33–21.66). The following factors had a statistically significant, positive impact on progression-free survival: patient age of less than 50 years (median progression-free survival was 29.43, vs 13.9 months for those aged 50 years or older; p = 0.004) and disease-free interval of 2 years or more (median progression-free survival was 51.66, vs 13.9 months for those with less than 2 years disease-free interval).Conclusion:Re-irradiation of second primaries or recurrences of head and neck cancers with moderate radiation doses yields acceptable progression-free survival and morbidity rates.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 540-540 ◽  
Author(s):  
Gunnar Folprecht ◽  
Thomas Gruenberger ◽  
Wolf Bechstein ◽  
Florian Lordick ◽  
Hauke Lang ◽  
...  

540 Background: Non-resectable liver metastases (mets) can be resected if they responded to systemic treatment. Cetuximab increases response rates in patients with k-ras wild type (wt) tumours. Methods: Patients (pts) with non-resectable liver mets (defined as technically non-resectable or ≥ 5 liver mets) were randomized to cetuximab/FOLFOX (arm A) or cetuximab/FOLFIRI (arm B). Resectability was re-evaluated after four and then every 2 months. Resection was offered to pts who became resectable during treatment. (Folprecht et al, Lancet Oncol 2010) Progression free survival (PFS) and overall survival (OS) were analysed in June 2011. Results: One hundred nine pts were randomized to cetuximab/FOLFOX or cetuximab/FOLFIRI, 106 evaluable for response. The median OS in all pts was 33.1 months [95% CI: 25.8-40.4], 35.7 [29.9-41.6] mo. in arm A and 29.0 [18.1-39.8] mo. in arm B (HR 1.09 [0.69-1.72]). The 4-year OS was 28% in all pts. The PFS was 11.2 [7.2-15.3] and 10.5 [8.9-12.2] mo. in arm A and B, respectively (HR 1.15 [0.77-1.70]). According to the k-ras mutational status, the OS and PFS was 36.1 [24.4-47.8] and 11.9 [8.25-15.6] in k-ras wt, 27.4 [15.7-39.1] and 9.9 [4.5-15.2] in k-ras mutant pts. In the k-ras wt subset, the OS was 35.8 [30.2-41.4] and 41.6 [24.8-58.5] mo. in arm A and B (HR 1.01 [0.55-1.86]), the PFS 12.1 [5.2-19.1] and 11.5 [8.8-14.1] mo. in arm A and B (HR 1.09 [0.66-1.79]). Pts with R0 resection had a significantly longer OS (median 46.7 [30.7-62.7] mo.) than pts without (median OS: 27.3 [21.2-33.3] mo, p=0.002). In R0 resected pts, the 3- and 4 year OS was 64% and 49%. The median disease free survival (DFS) was 9.9 mo after R0 resection, the 2 year DFS 19%. According to a review of CT/MRI scans which was performed by surgeons blinded to all clinical data, there was no survival difference between “resectable” pts and pts not categorized as “resectable” at baseline (HR 0.81 [0.44-1.50]), but a significantly better OS was observed for pts regarded as “resectable” after treatment vs. other categories (HR 0.47 [0.27-0.83], p=0.007). Conclusions: Pts had a favourable overall survival which was longer in R0 resected pts. Resectability after treatment seems to be important for the pts outcome.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 946-946 ◽  
Author(s):  
Joseph R. Mikhael ◽  
Sahar Zadeh ◽  
Sara Samiee ◽  
Keith Stewart ◽  
Christine Chen ◽  
...  

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%


2003 ◽  
Vol 13 (4) ◽  
pp. 497-504 ◽  
Author(s):  
Y. Eralp ◽  
P. Saip ◽  
B. Sakar ◽  
S. Kucucuk ◽  
A. Aydiner ◽  
...  

The aim of this study is to identify the impact of various prognostic factors on survival in patients with recurrent carcinoma of the uterine cervix. Fifty-two patients who were treated with platinum-based chemotherapy for recurrent or metastatic disease were retrospectively evaluated. Twenty-seven patients (90%) had received pelvic radiation as primary treatment.Out of 45 evaluable patients, two (4.4%) had complete response (CR), three (6.7%) had a continuous CR after additional surgical treatment and irradiation. Five patients (11.1%) had partial response (PR). The majority of patients had progressive response to treatment (22 patients, 48.9%). After a median follow-up period of 19 months, 31 patients (60%) had died. Progression-free survival after initial diagnosis was observed to have a significant association with response to chemotherapy for recurrent disease (Fisher two-sided P = 0.027). The median survival duration for relapsed disease was 11.8 months. Those with a longer disease-free interval (8 months vs. ≤ 8 months) from initial diagnosis to first recurrence and reponse to chemotherapy had a tendency for a longer survival duration after relapse by univariate analysis. Multivariate analysis revealed that progressive response to chemotherapy (P = 0.002, HR = 4.6) and recurrence within the previously irradiated field (P = 0.04, HR = 2.7) were significant independent prognostic factors for a shorter time to progression after recurrence. Furthermore, advanced stage at presentation (P = 0.001, HR = 3.0) and a short disease-free interval after primary treatment (<8 months, P = 0.003, HR = 3.4) were determined as independent prognostic factors with a significant negative influence on progression-free survival and overall survival from initial diagnosis, respectively.The use of toxic and expensive combinations for the treatment of recurrent cervical cancer patients should be well balanced against potential hazards. Based on our data, less toxic regimens would be more feasible in patients who present with advanced disease at initial diagnosis, or those that experience recurrence within the previously irradiated field after a progression-free interval of less than 8 months.


2021 ◽  
Vol 69 (4) ◽  
pp. 888-892
Author(s):  
Joseph I Clark ◽  
Brendan Curti ◽  
Elizabeth J Davis ◽  
Howard Kaufman ◽  
Asim Amin ◽  
...  

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.


2021 ◽  
Vol 31 (3) ◽  
pp. 208-217
Author(s):  
Alexandra Frelau ◽  
Eva Jali ◽  
Boris Campillo-Gimenez ◽  
Marc Pracht ◽  
Marc Porneuf ◽  
...  

2018 ◽  
Vol 50 (1) ◽  
pp. 66-78 ◽  
Author(s):  
Qingyan Mao ◽  
Zhen Chen ◽  
Kun Wang ◽  
Renfang Xu ◽  
Hao Lu ◽  
...  

Background/Aims: Several recent studies have demonstrated that Stathmin 1expression may be closely associated with prognosis in patients with various types of cancers. In the present study, we conducted a meta-analysis of all available studies in the English literature to assess the prognostic value of Stathmin 1expression in patients with solid cancers. Methods: The online databases PubMed, Embase, and Web of Science were searched for literature regarding Stathmin 1 and its association with patient outcomes associated with solid cancers. Results: A total of 23 articles including 26 studies that contained 5 335 patients were retrieved and analyzed. Our results indicated that high Stathmin 1 expression yielded a worse overall survival (OS) (hazard ratio [HR] = 2.17, 95% confidence interval [CI]: 1.81–2.60), disease-free survival (DFS) (HR = 2.46, 95% CI: 2.00–3.02), disease-specific survival (DSS) (HR = 1.98, 95% CI: 1.58– 2.47) and progression-free survival (PFS)/recurrence-free survival (RFS) (HR = 2.09, 95% CI: 1.51–2.89). Furthermore, the association of high Stathmin 1 expression with poor survival was significant even for sub-group analyses of different tumor types, ethnicities, methods used to calculate HRs, detected methods, and analysis types. Conclusion: In summary, this meta-analysis determined that high Stathmin 1 expression is associated with poor prognosis in patients with solid cancers and expression of this protein could be a clinically useful prognostic biomarker.


2020 ◽  
Vol 26 (7) ◽  
pp. 1754-1758
Author(s):  
Mesut Yilmaz ◽  
Şermin Güven Meşe

Introduction Patients with distant metastatic melanoma has a poor prognosis, with a reported median survival time of six to eight months. In modern era, survival has prolonged with the immunotherapy and targeted therapy options. Potent and selective BRAF inhibitors have been developed that specifically inhibit mutated BRAF over other RAF kinases. Vemurafenib was the first selective tyrosine kinase inhibitor developed to target the V600E allele of BRAF-mutant melanoma. Case Report In this report, we present a case of BRAFV600E-mutant metastatic melanoma, which is being treated with vemurafenib monotherapy with complete response for about seven years. Management and Outcome The patient is still being treated with vemurafenib and radiologic complete response is ongoing for about seven years. Discussion Patients treated with BRAF inhibitors monotherapy had promising response rates and improvement in the progression-free survival and overall survival, but melanoma cells became resistant very quickly, affecting the progression. In this case, we present a case that has permanent response to vemurafenib monotherapy.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Francesco Gaudio ◽  
Annamaria Giordano ◽  
Vincenzo Pavone ◽  
Tommasina Perrone ◽  
Paola Curci ◽  
...  

Recurrences of Hodgkin's Lymphoma (HL) 5 years after the initial therapy are rare. The aim of this study is to report a single centre experience of the clinical characteristics, outcome, and toxicity of pts who experienced very late relapses, defined as relapses that occurred 5 or more years after the achievement of first complete remission. Of 532 consecutive pts with classical HL treated at our Institute from 1985 to 1999, 452 pts (85%) achieved a complete remission. Relapse occurred in 151 pts: 135 (29.8%) within 5 years and 16 over 5 years (3.5%, very late relapses). Very late relapses occurred after a median disease-free interval of 7 years (range: 5–18). Salvage treatment induced complete remission in 14 pts (87.5%). At a median of 4 years after therapy for very late relapse, 10 pts (63%) are still alive and free of disease and 6 (37%) died (1 from progressive HL, 1 from cardiac disease, 1 from thromboembolic disease, 1 from HCV reactivation, and 2 from bacterial infection). The probability of failure-free survival at 5 years was 75%. The majority of deaths are due to treatment-related complications. Therapy regimens for very late relapse HL are warranted to minimize complications.


2018 ◽  
Vol 33 (4) ◽  
pp. 372-378 ◽  
Author(s):  
Yuanyuan Hu ◽  
Jie Shen ◽  
RuiKe Liu ◽  
ZhiMei Feng ◽  
ChangNing Zhang ◽  
...  

Background: The pretreatment prognostic nutritional index has been considered a potential prognostic biomarker in patients with non-small cell lung cancer (NSCLC), but this remains controversial. Therefore, we performed a meta-analysis to systematically assess the prognostic value of the prognostic nutritional index in patients with NSCLC. Methods: We systematically searched PubMed, EMBASE, Web of Science, and CNKI. The hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were used to evaluate the link between the prognostic nutritional index and the oncological outcomes of patients with NSCLC, including overall survival, disease-free survival/recurrence-free survival, and progression-free survival. Results: Fifteen studies were included in this meta-analysis. Twelve of these studies explored the association between the prognostic nutritional index and the overall survival of patients with NSCLC. Our pooled analysis indicated that a low prognostic nutritional index was significantly related to adverse overall survival (HR 1.61; 95% CI 1.44, 1.81; P < 0.001). Our results also showed that the prognostic nutritional index was a negative predictor for disease-free survival/recurrence-free survival, and progression-free survival in patients with NSCLC. Conclusion: Our meta-analysis demonstrated that there was a close association between the prognostic nutritional index value and prognosis in NSCLC patients and that the prognostic nutritional index may act as a useful prognostic biomarker in NSCLC patients.


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