Post-recurrence Overall Survival Research Articles

Bevacizumab and gamma knife radiosurgery for first-recurrence glioblastoma

IntroductionGlioblastoma (GBM) is the most common central nervous system malignancy in adults. Despite decades of developments in surgical management, radiation treatment, chemotherapy, and tumor treating field therapy, GBM remains an ultimately fatal disease. There is currently no definitive standard of care for patients with recurrent glioblastoma (rGBM) following failure of initial management.ObjectiveIn this retrospective cohort study, we set out to examine the relative effects of bevacizumab and Gamma Knife radiosurgery on progression-free survival (PFS) and overall survival (OS) in patients with GBM at first-recurrence.MethodsWe conducted a retrospective review of all patients with rGBM who underwent treatment with bevacizumab and/or Gamma Knife radiosurgery at Roswell Park Comprehensive Cancer Center between 2012 and 2022. Mean PFS and OS were determined for each of our three treatment groups: Bevacizumab Only, Bevacizumab Plus Gamma Knife, and Gamma Knife Only.ResultsPatients in the combined treatment group demonstrated longer post-recurrence median PFS (7.7 months) and median OS (11.5 months) compared to glioblastoma patients previously reported in the literature, and showed improvements in total PFS (p=0.015), total OS (p=0.0050), post-recurrence PFS (p=0.018), and post-recurrence OS (p=0.0082) compared to patients who received either bevacizumab or Gamma Knife as monotherapy.ConclusionThis study demonstrates that the combined use of bevacizumab with concurrent stereotactic radiosurgery can have improve survival in patients with rGBM.

Treatment patterns and results of salvage treatment for regional recurrences after stereotactic ablative radiotherapy for primary non-small cell lung cancer.

Stereotactic ablative radiotherapy (SABR) for early-stage lung cancer has shown promising results; however, regional recurrence (RR) development is not uncommon, and salvage treatment strategies have not been established. We aimed to investigate treatment patterns, prognostic factors, and survival outcomes. A retrospective analysis of 391 patients who underwent SABR for primary lung cancer from 2012 to 2019 was performed. Among these patients, 90 patients showed recurrence, including local recurrence (n=9), RR (n=33), distant metastasis (DM) (n=57), and RR with simultaneous DM (n=8). The median follow-up duration was 17.3 months. The median age was 75 years, and most patients underwent primary SABR due to poor lung function (69.7%). Various salvage treatments were performed in cases of RR, including chemotherapy (n=15), radiotherapy (n=7), concurrent chemoradiotherapy (n=2), and best supportive care (n=9). The median overall survival (OS) and post-recurrence OS (PR-OS) were 22.9 and 11.2 months, respectively. In multivariate analysis, age ≤75 years (HR=0.36, p=0.040), isolated recurrence (HR=0.34, p=0.037), and radiotherapy without chemotherapy (HR=0.25, p=0.024) were significant prognostic factors for PR-OS. Despite various salvage treatments, PR-OS was less than 1 year after RR in our frail patients group who underwent primary SABR. The toxicities of salvage chemotherapy could be quite severe; thus, careful patient selection is required. Further research is needed to validate our findings.

Prognostic factors after isolated ipsilateral local and regional recurrence in HER2-negative luminal breast cancer: a multi-center retrospective study

BackgroundAlthough the incidence of isolated ipsilateral local and regional recurrence (IILRR) in human epidermal growth factor 2 (HER2)-negative luminal breast cancer is low, it is important because of its potential risk of distant metastasis and breast cancer related mortality. The aim of this study was to investigate prognostic factor and survival of IILRR using a large multi-center cohort.MethodsData on patients with HER2-negative luminal breast cancer between 2005 and 2015 were retrieved. The endpoint was IILRR rate, post-recurrence progression-free survival (P-PFS), and post-recurrence overall survival (P-OS). Prognostic factors for progression and overall survival (OS) after IILRR were assessed by multivariate analysis.ResultsEighty (2.37%) patients experienced IILRR. Of them, 27 (33.7%) experienced a disease progression, including 23 (85.2%) who had distant metastasis. The median DFS was 48.5 months (range, 4–138 months). In 72.5% of cases, the first IILRR occurred after 3 years. Estimated 5-year P-PFS rates were 86.2%, 69.7%, 69.0%, 42.7%, and 82.2% for patients with age < 40 at diagnosis (p = 0.015), T1 stage (p = 0.012), stage I (p < 0.001), lymphovascular invasion (p = 0.003), and patients with post-recurrence endocrine therapy (p < 0.001), respectively. The 5-year Kaplan–Meier P-OS rate for patients was 81.4%. Post-recurrence endocrine therapy was independent factor for progression (HR: 0.176, p < 0.001) and OS (HR: 0.080, p < 0.001).ConclusionsAlthough there is no standardized treatment for IILRR yet, endocrine therapy after local resection plays a more important role in improving prognosis than chemotherapy or radiotherapy in HER2-negative luminal breast cancer.

Randomized phase II/III trial of veliparib or placebo in combination with adjuvant temozolomide in newly diagnosed glioblastoma (GBM) patients with MGMT promoter hypermethylation (Alliance A071102).

2001 Background: PolyADP-ribose polymerase (PARP) is an important modulator of DNA repair following temozolomide (TMZ) therapy. Pre-clinical testing demonstrated significant survival benefit for the combination of TMZ and PARP inhibitor veliparib in a subset of GBM pt-derived xenografts with MGMT promoter hypermethylation. Methods: After central pathology review and MGMT testing, patients (pts) with newly diagnosed, MGMT promoter hypermethylated GBM who had completed concurrent radiation and TMZ were randomized to adjuvant therapy with TMZ (Days 1-5 q28 days) combined with either placebo or veliparib (Days 1-7 q28 days). Veliparib/placebo+TMZ treatment was continued for up to 6 cycles. Pts accrued on the phase II and III portions of the trial were included in the primary endpoint analysis of overall survival (OS), with 90% power to detect a hazard ratio of 0.71 using a one-sided log-rank test with type I error rate of 0.05. The planned phase III sample size was 400 pts with data maturity after 302 deaths. Results: The phase II and III portions of the trial were open to accrual from 12/15/2014 to 2/6/2017 and 11/8/2017 to 10/15/2018, respectively; 447 pts were accrued to the trial and used in this intention to treat analysis. The two treatment groups were well balanced for prognostic factors, 421 pts initiated treatment, median follow-up was 57.8 months (mos), 380 pts had disease progression and 335 pts have died. There was no difference in OS (p = 0.15; HR 0.89 (0.71-1.11), median OS 28.1 vs. 24.8 mo. for TMZ+veliparib vs. TMZ+placebo, respectively) and no difference in secondary endpoint progression free survival (PFS, p = 0.31; HR 1.05 (0.86-1.30), median 13.2 vs. 12.1 mo, respectively). There was a notable trend for extended OS with TMZ+veliparib treatment at intermediate time-points between 24 and 42 mos (3-year OS 36.6% vs. 28.9% with TMZ+placebo, p = 0.09). In an unplanned exploratory analysis, treatment with TMZ at the time of first recurrence was associated with extended post-recurrence OS (p = 0.03) for pts treated on the experimental arm; median post-recurrence OS with TMZ salvage was 17.0 mo in the TMZ+veliparib arm and 12.6 mo in the TMZ+placebo arm, as compared to 9.6 mo in either arm if TMZ salvage was not used. These data are consistent with a possible effect of veliparib limiting the emergence of TMZ resistance in a subset of GBM pts. Conclusions: Veliparib combined with adjuvant TMZ therapy was not associated with significant extension in OS or PFS in newly diagnosed, MGMT hypermethylated GBM pts. However, a subset of pts treated with TMZ+veliparib may have an extended survival following re-treatment with TMZ at first recurrence. Clinical trial information: NCT02152982.

Hepatectomy or/with Metastatectomy for Recurrent Intrahepatic Cholangiocarcinoma: Of Promise for Selected Patients.

Introduction: Intrahepatic cholangiocarcinoma (ICC) has devastating outcomes owing to its advanced stage at diagnosis and high recurrence after hepatectomy. There is no preferred treatment for recurrent ICC. We retrospectively reviewed our patients who underwent repeated operations for recurrent ICCs based on their different indications to appraise the outcomes. Methods: In all, 160 out of 216 patients with ICC (71.4%) experienced recurrence after curative resection from 1977 to 2014. The patterns of recurrence were categorized according to the locations and numbers of recurrent tumors. Results: Patients with merely intrahepatic recurrence (n = 38) had superior overall survival (OS) compared with those with beyond intrahepatic recurrence (p < 0.0001). Twenty-seven out of 160 patients (16.8%) underwent repeat hepatectomy or/with metastatectomy for recurrence and had superior OS when compared to the remaining 133 patients who received nonoperative treatment/palliation (85.6 months versus 20.9 months, p < 0.001). Furthermore, patients suitable for repeat hepatectomy in the intrahepatic recurrent group (n = 12) had superior post-recurrence overall survival (PROS) than the remaining 26 patients receiving nonoperative treatment (61.6 months versus 14.7 months, p < 0.05). Conclusion: Liver is the most commonly involved site of recurrent ICC. However, merely intrahepatic recurrence may have a favorable prognosis compared to recurrence involving other sites. Aggressive hepatectomy may provide a survival benefit in selected patients.

Selection of Treatment Regimens for Recurrent Cervical Cancer.

ObjectiveThe selection of individualized treatment for recurrent cervical cancer is challenging. This study aimed to investigate the impact of various therapies on survival outcomes after recurrence.MethodsEligible patients were diagnosed with recurrent cervical cancer between March 2012 and April 2018. Postrecurrence progression-free survival (PFS) and overall survival (OS) were investigated in the whole cohort and in subgroups, categorized by recurrence site and prior radiotherapy history, using a multivariate model that incorporated treatment for primary and recurrent tumors, histological pathology, and FIGO staging.ResultsTwo hundred and sixty recurrent cervical cancer patients were included. As of March 1, 2020, the median postrecurrence PFS and OS were 7.0 (range 0-94) and 24.0 (1.8-149.1) months, respectively. In a multivariate model measured by PFS, radiotherapy was superior to other therapies for the whole cohort (p=0.029) and recurrence only within the pelvic cavity (p=0.005), but the advantages of radiotherapy disappeared in patients with a history of radiotherapy (p values >0.05). For recurrence only beyond the pelvic cavity, combination therapy resulted in improved PFS (p=0.028). For recurrence both within and beyond the pelvic cavity, no therapy regimen provided additional PFS benefits (p values >0.05). Radiotherapy and combination therapy were also associated with improved postrecurrence OS for recurrence within the pelvic cavity (p=0.034) and only beyond the pelvic cavity (p=0.017), respectively.ConclusionsIn cervical cancer patients, postrecurrence radiotherapy can improve PFS and OS for patients with recurrence within the pelvic cavity and without prior radiotherapy. For recurrence beyond the pelvic cavity or cases with a history of radiotherapy, combination or individualized therapy may provide potential survival benefits.

Clinical Characteristics and Prognostic Factors of Early and Late Recurrence After Definitive Radiotherapy for Nasopharyngeal Carcinoma.

We investigated the clinical characteristics, prognostic factors, and post-recurrence prognostic factors of early- and late-recurrence patients for nasopharyngeal carcinoma (NPC) after definitive intensity-modulated radiation therapy (IMRT). This was a single-center retrospective analysis of patients in China from January 2010 to December 2015. The prognostic factors for overall survival (OS) and post-recurrence OS of early- and late-recurrence patients were identified using univariate and multivariate Cox regression analyses. Of the 9,468 patients included, 409 (4.3%), 325 (3.4%), and 182(1.9%) developed purely local recurrence, purely regional recurrence, and locoregional recurrence during follow-up, respectively. In the purely local recurrence group, 192 patients (46.9%) developed early local recurrence (ETR), and 217 patients (53.1%) developed late local recurrence (LTR). Of the 192 ETR patients, multivariate Cox regression analysis revealed that age and gender were independent risk factors of OS, and post-recurrence best supportive treatment (PRBST) was associated with poorer post-recurrence OS. Of the 217 LTR patients, the results revealed that baseline value of EBV-DNA was an independent risk factor for OS, while PRBST was associated with poorer post-recurrence OS. In the purely regional recurrence group, 183 patients (56.3%) developed early regional recurrence (ENR), and 142 patients (43.7%) developed late regional recurrence (LNR). Of the 183 ENR patients, multivariate Cox regression analysis revealed that alcohol abuse and TNM stage were independent risk factors of OS, while alcohol drinkers and PRBST were associated with poorer post-recurrence OS. Of the 142 LNR patients, PRBST was associated with poorer post-recurrence OS. In the locoregional recurrence group, 87 patients (47.8%) developed early locoregional recurrence (ELR), and 95 patients (52.2%) developed late locoregional recurrence (LLR). Of the 87 ELR patients, multivariate Cox regression analysis revealed that N stage and TNM stage were independent risk factors of OS, and N2/3 stage and PRBST were associated with poorer post-recurrence OS. Of the 95 LLR patients, the results revealed that T stage was an independent risk factor for OS, while T3/4 stage and PRBST were associated with poorer post-recurrence OS. Patients with LTR/LNR/LLR demonstrate significantly better OS compared with patients with ETR/ENR/ELR, Nevertheless, post-recurrence OS between patients with ETR/ENR/ELR and LTR/LNR/LLR was not significantly different.

Primary 21-Gene Recurrence Score and Disease Outcome in Loco-Regional and Distant Recurrent Breast Cancer Patients.

Background: The 21-gene recurrence score (RS) assay has been proven prognostic and predictive for hormone receptor-positive/HER2-negative, node-negative early breast cancer patients. However, whether primary 21-gene RS can predict prognosis in recurrent breast cancer patients remained unknown.Patients and Methods: Consecutive breast cancer patients operated in Comprehensive Breast Health Center, Shanghai Ruijin Hospital between January 2009 and December 2018 were retrospectively analyzed. Patients with available 21-gene RS result for the primary tumor and reporting disease recurrence during follow-up were included. Association of 21-gene RS and overall survival (OS), post-recurrence overall survival (PR-OS), post-recurrence progression-free survival (PR-PFS), and first-line systemic treatment after recurrence were compared among different groups.Results: A total of 74 recurrent patients were included, with 10, 27, 37 patients in the RS <18, 18–30, and ≥ 31 groups, respectively. Recurrent patients with RS ≥ 31 were more likely to receive chemotherapy as their first-line treatment compared to those with RS <31 (P = 0.025). Compared to those with RS <31, patients with RS ≥ 31 had significantly worse OS (P = 0.025), worse PR-OS (P = 0.026), and a trend of inferior PR-PFS (P = 0.106). Multivariate analysis demonstrated that primary ER expression level (OS: P = 0.009; PR-OS: P = 0.017) and histological grade (OS: P = 0.003; PR-OS: P = 0.009), but not primary 21-gene RS (OS: P = 0.706; PR-OS: P = 0.120), were independently associated with worse OS and PR-OS.Conclusions: High primary 21-gene RS tended to be associated with worse disease outcome in loco-regional and distant recurrent breast cancer patients, which could influence the first-line systemic treatment after relapse, warranting further clinical evaluation.

Identification of Patients with Brain Metastases with Favorable Prognosis After Local and Distant Recurrence Following Stereotactic Radiosurgery.

PurposeThis retrospective study aimed to determine the prognostic factors associated with overall survival after intracranial local and distant recurrence in patients undergoing stereotactic radiosurgery (SRS) for brain metastases.Patients and MethodsClinical characteristics and therapeutic parameters of 251 patients, who were treated with initial stereotactic radiosurgery for brain metastases and later experienced intracranial recurrence, were analyzed to identify prognostic factors of post-recurrence overall survival (PROS). A Cox proportional hazard model was applied for univariate and multivariate analyses.ResultsAmong the 251 patients, the median post-recurrence overall survival was 8 months, and the six-month PROS rate was 60.2%. The interval from initial radiosurgery treatment to intracranial recurrence (hazard ratio [HR]:0.970), the number of brain recurrent tumors (HR:1.245), the number of extracranial metastatic organs (HR:1.183), recursive partition analysis (RPA) (HR:1.778), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (HR:2.442) were identified as independent prognostic factors. The patients who received local treatment for solitary brain recurrence achieved better survival (the median survival time after recurrence was 22 months). In patients without extracranial metastasis, the median post-recurrence overall survival of the local treatment group was longer than that in the whole brain radiation therapy (WBRT) group (P<0.001) and the systemic therapy group (P<0.001).ConclusionA shorter interval from initial stereotactic radiosurgery to recurrence, an increasing number of brain recurrences and extracranial metastatic organs, and poor RPA and ECOG PS values are associated with poor post-recurrence prognosis. When the number of brain recurrent tumors and extracranial metastatic organs was limited, local treatment including stereotactic radiosurgery, surgery or intensity-modulated radiation therapy (IMRT) improved the post-recurrence overall survival.

Identifying Long-Term Survival Candidates among Patients with Isolated Locoregionally Recurrent Breast Cancer: Implications of the Use of Systemic Chemotherapy.

PurposeWe aimed to investigate the clinicopathologic factors associated with distant metastasis (DM) and post-recurrence overall survival (OS) after salvage treatments for isolated locoregional recurrence (ILRR) of breast cancer and identify long-term surviving patients for providing a more personalized therapy.MethodsWe analyzed 125 patients who underwent salvage local treatments for ILRR after initial curative breast surgery.ResultsFifty-two (41.6%) patients experienced secondary recurrence or disease progression, of which 20 (38.5%) experienced a secondary locoregional recurrence and 40 (76.9%) experienced DM as the first site of failure. In multivariate analysis of distant metastasis free survival (DMFS) and post-recurrence OS, the initial pN2-3 stage, a disease-free interval of < 36 months, and non-curative resection for recurrent disease were independently poor prognosticators. The score for patients stratified according to the number of risk factors increased from 0 to 3; the corresponding 5-year DMFS rates were 91.4%, 53.0%, 35.9%, and 0% and the 5-year OS rates were 97.3%, 70.4%, 32.7%, and 25.0%, respectively (p < 0.001). Systemic chemotherapy reduced DM in patients with a score of 2–3, but it did not in those with a score of 0-1.ConclusionOur collective stratification can help with prognosis prediction for ILRR of breast cancer. Depending on the DM risk of patients, the potential combination of systemic therapy should be discussed further.

Definitive Local Therapy for Oligo-recurrence in Patients With Completely Resected Non-small Cell Lung Cancer.

The aim of this study was to elucidate a curable subgroup among patients with non-small cell lung cancer (NSCLC) who developed postoperative recurrence. Between 1986 and 2012, among the 1408 patients who underwent complete anatomic lung resection for NSCLC at our institution, 420 developed recurrence. After excluding 14 patients with insufficient information about recurrence, 406 were included in this retrospective study. We investigated the association between several clinicopathologic factors and postrecurrence overall survival (PR-OS) and postrecurrence progression-free survival (PR-PFS). The 5-year PR-OS and PR-PFS rates were 14.0% and 5.9%, respectively. By multivariate analysis, female sex, longer disease-free interval, specific targeted therapy, recent recurrence, oligo-recurrence, and definitive local therapy (DLT) were found to be independent favorable prognostic factors for both PR-OS and PR-PFS. Among these 6 prognostic factors, although female sex, longer disease-free interval, and specific targeted therapy were associated with a prolonged median PR-PFS time, they were not associated with an improved 5-year PR-PFS rate. In contrast, recent recurrence, oligo-recurrence, and DLT were associated with improvement in both the median PR-PFS time and 5-year PR-PFS rate. We found that recent recurrence, oligo-recurrence, and DLT were associated with an improved median PR-PFS time and long-term PR-PFS rate in patients with postoperative recurrence after complete resection of NSCLC. On the basis of these results, we believe that DLT should be considered first for patients with oligo-recurrence before applying noncurative treatment.

Postoperative Imaging and Tumor Marker Surveillance in Resected Pancreatic Cancer.

Background: Pancreatic cancer is a catastrophic disease with high recurrence and death rates, even in early stages. Early detection and early treatment improve survival in many cancer types but have not yet been clearly documented to do so in pancreatic cancer. In this study, we assessed the benefit on survival resulting from different patterns of surveillance in daily practice after curative surgery of early pancreatic cancer. Methods: Patients with pancreatic ductal adenocarcinoma who had received curative surgery between January 2000 and December 2013 at our institute were retrospectively reviewed. Patients were classified into one of four groups, based on surveillance strategy: the symptom group, the imaging group, the marker group (carbohydrate antigen 19-9 and/or carcinoembryonic antigen), and the intense group (both imaging and tumor marker assessment). Overall survival (OS), relapse-free survival (RFS), and post-recurrence overall survival (PROS) were evaluated. Results: One hundred and eighty-one patients with documented recurrence or metastasis were included in our analysis. The median OS for patients in the symptom group, imaging group, marker group, and intense group were 21.4 months, 13.9 months, 20.5 months, and 16.5 months, respectively (p = 0.670). Surveillance with imaging, tumor markers, or both was not an independent risk factor for OS in univariate and multivariate analyses. There was no significant difference in median RFS (symptom group, 11.7 months; imaging group, 6.3 months; marker group, 9.3 months; intense group, 6.9 months; p = 0.259) or median PROS (symptom group, 6.9 months; imaging group, 7.5 months; marker group, 5.0 months; intense group, 7.8 months; p = 0.953) between the four groups. Multivariate analyses identified poor Eastern Cooperative Oncology Group Performance Status (ECOG PS) (≥1), primary tumor site (tail), and tumor grade (poor differentiation) were poor prognostic factors for OS. Conclusions: Surveillance with regular imaging, tumor marker, or both was not an independent risk factor for OS of pancreatic cancer patients who undergo curative tumor resection.

Stage-specific disease recurrence and survival in localized and regionally advanced cutaneous melanoma

ObjectiveTo investigate stage-specific survival from diagnosis, stage-specific disease recurrence, and post-recurrence survival in patients diagnosed with localized and regionally advanced cutaneous melanoma. MethodsA retrospective, observational cohort study was conducted in six Dutch hospitals. We included patients with a first diagnosis of stage I, II, or III melanoma between January 2003 and December 2011. Descriptive statistics were used to summarize time to first recurrence and type of first recurrence. Overall survival (OS) from diagnosis and post-recurrence OS were assessed using the Kaplan-Meier method. ResultsA total of 3,093 patients had a first diagnosis of stage I (n = 2,299), II (n = 565), or III (n = 229) melanoma. Median OS was not yet reached for patients with stage I, 9.5 years for patients with stage II, and 6.8 years for patients with stage III. Fifty-seven patients (8%) with stage IB, 137 patients (29%) with stage II, and 81 patients (47%) with stage III developed disease recurrence. Median time to first recurrence was 2.8, 1.5, and 1.0 years for patients with stage IB, II, and III, respectively. Most patients (79%) developed regional lymph node or distant metastases as first recurrence. Median post-recurrence OS was 2.8, 3.9, and 0.5 years for patients with intralymphatic, regional lymph node, and distant metastases, respectively. ConclusionA substantial number of patients developed disease recurrence. Of these patients, a considerably high proportion developed distant metastases which had a great impact on survival. Identifying disease recurrence at its earliest stage is crucial because metastatic melanoma remains incurable for most patients.

Prognostic significance of primary tumor localization in stage II and III colon cancer.

AIMTo investigate the effects of tumor localization on disease free survival (DFS) and overall survival (OS) in patients with stage II-III colon cancer.METHODSThis retrospective study included 942 patients with stage II and III colon cancer, which were followed up in our clinics between 1995 and 2017. The tumors from the caecum to splenic flexure were defined as right colon cancer (RCC) and those from splenic flexure to the sigmoid colon as left colon cancer (LCC).RESULTSThe median age of the patients was 58 years (range: 19-94 years). Male patients constituted 54.2%. The rates of RCC and LCC were 48.4% (n = 456) and 51.6% (n = 486), respectively. During the median follow-up of 90 mo (range: 6-252 mo), 14.6% of patients developed recurrence and 9.1% of patients died. In patients with stage II and III disease with or without adjuvant therapy, DFS was similar in terms of primary tumor localization (stage II; P = 0.547 and P = 0.481, respectively; stage III; P = 0.976 and P = 0.978, respectively). In patients with stage II and III disease with or without adjuvant therapy, OS was not statistically significant with respect to primary tumor localization (stage II; P = 0.381 and P = 0.947, respectively; stage III; P = 0.378 and P = 0.904, respectively). The difference between median OS of recurrent RCC (26 ± 6.2 mo) and LCC (34 ± 4.9 mo) cases was eight months (P = 0.092).CONCLUSIONOur study showed no association of tumor localization with either DFS or OS in patients with stage II or III colon cancer managed with or without adjuvant therapy. However, post-recurrence OS appeared to be worse in RCC patients.

PRM21 - MODELLING SURVIVAL OF PATIENTS WITH COMPLETELY RESECTED ADVANCED MELANOMA WITH ADJUVANT TREATMENT OF NIVOLUMAB VERSUS OBSERVATION

Nivolumab demonstrated significant recurrence-free survival (RFS) gains vs. ipilimumab in the phase 3 trial CheckMate-238, whilst the phase 3 trial CA184-029 showed superior RFS gains for ipilimumab vs. placebo. Modelling was used to estimate overall survival (OS) associated with nivolumab compared to observation (no treatment) when OS data was not available in CheckMate-238. Four modelling options were developed using different methods and evidence sources to estimate post-recurrence survival (PRS) and OS. For all options, the RFS parametric survival curves for nivolumab and observation were informed by a patient-level data meta-regression of the two trials. The first option applied a partitioned survival model (PSM), where the parametric OS curve for observation was derived from the CA184-029 placebo arm, and nivolumab OS was based on a surrogacy relationship between RFS and OS specific to adjuvant melanoma. The other options used state-transition Markov models to estimate PRS from different data sources: (1) assumed PRS is identical to OS curves from the PSM, applying a PRS vs OS hazard ratio from CA184-029; (2) used weighted survival of local/regional recurrence data in CA184-029 and a network meta-analysis of advanced melanoma treatments and (3) used PRS from CA184-029. In all options, long-term melanoma registry data were applied to both treatment arms at 10 years. The PSM estimated 21.1 and 13.9 life-years (LYs) for nivolumab and observation, respectively over a life time horizon. Markov option 1 reported 18.5 and 11.1 LYs, option 2 reported 13.9 and 9.1 LYs, and option 3 reported 17.0 and 12.1 LYs for nivolumab and observation, respectively. Modelling can be used to estimate OS for nivolumab and observation. Different modelling methods and evidence sources all predicted superior OS for nivolumab vs. observation, but with varying LY differences. Longer term OS data are required to validate these modelling options.

Characterization of Late Recurrence After Radical Cystectomy in a Large Multicenter Cohort of Bladder Cancer Patients

To investigate the characteristics and outcomes of late recurrence (LR) in patients with bladder cancer (BCa) treated with radical cystectomy (RC) and to identify clinicopathologic predictors of LR and postrecurrence survival. This multicenter study included 1652 BCa patients. LR was defined as occurring more than 5 years after RC. Differences in postrecurrence overall survival according to the timing of disease recurrence and the location of recurrence were calculated using the log-rank test. A logistic regression model was used to identify predictors of LR, and Cox regression models were used to evaluate variables associated with postrecurrence overall survival (OS). Overall, 548 patients experienced disease recurrence. Of these, 67 patients (12.2%) experienced LR, with a median time to recurrence of 86 months (interquartile range 70.5-107.2). LR was more likely to be located in the urothelium (P = .005). On multivariable analysis, younger age (P = .008) and non-organ confined disease (P = .03) were found to be predictors of LR. Postrecurrence 5-year OS was worse in patients who experienced early recurrence compared with those with LR (12% vs 25%, P = .02) and in those with nonurothelial recurrence compared to those with disease recurrence in the remaining urothelium (12% vs 51%, P < .001). Older age (P < .001), non-organ confined disease at RC (P = .02), and nonurothelial recurrence site (P = .002) were independently associated with postrecurrence OS. LR after RC is an uncommon but non-negligible event that harbors unique characteristics. LR is associated with better OS compared to early recurrence. Our findings reinforce the need for lifelong follow-up of BCa patients after RC.

A multi-institutional study of immunosuppressed and immunocompetent patients with cutaneous squamous cell carcinoma of the head and neck treated with definitive surgery and radiotherapy: Outcomes after disease recurrence.

63 Background: Our multi-institutional group previously demonstrated that immunosuppressed (IS) patients with cutaneous squamous cell cancer of the head and neck (cSCC-HN) treated with surgery and adjuvant radiotherapy had inferior survival compared to immunocompetent (IC) patients. This study further examines those patients who experienced disease recurrence and compares the impact of immune status on overall survival after recurrence. Methods: Pts who received surgical resection and postoperative RT for primary or recurrent, stage I-IV (non-metastatic) cSCC-HN between 1995-2015 at Cleveland Clinic, Washington University St. Louis, and University of California San Francisco were included in this IRB approved study. Pts were categorized as IS if they were diagnosed with chronic hematologic malignancy, HIV/AIDS, or were treated with immunosuppressive therapy for organ transplantation ≥ 6 months prior to diagnosis. Pts with recurrence included those who experienced local, regional, or distant failure after completion of definitive surgery and radiation. Overall survival (OS) and progression free survival (PFS) were calculated using the Kaplan Meier method. Results: In the initial study of 205 pts, 138 (67.3%) were immunocompetent (IC) and 67 (32.7%) were IS, and were followed for a median of 25 months. PFS was significantly lower in IS pts compared to IC at 2 years (38.7% vs. 71.6%; p = 0.002), while 2yr OS demonstrated a similar but non-significant trend (60.9% vs. 78.1%; p = 0.135). A total of 72 patients (35%) recurred, including 31 with distant failure. 1yr post-recurrence OS was 42% with a median survival of 8.4 months. Median survival did not significantly differ between the IS and IC groups (8.0 vs. 12.9 months; p = 0.9). Conclusions: Pts with cSCC-HN who experience disease recurrence after definitive treatment with surgery and radiation have poor survival, irrespective of immune status. Clinical trials testing immunotherapies are needed for both IC and IS patients with this understudied disease.

Risk stratification and prognostic nomogram for post-recurrence overall survival in patients with recurrent extrahepatic cholangiocarcinoma

BackgroundThis study aimed to investigate post-recurrence overall survival (PROS) in patients with recurrent extrahepatic cholangiocarcinoma (EHC) and to indicate which groups of patients need active salvage treatments. MethodsWe retrospectively reviewed the records of 251 consecutive patients who underwent curative surgery followed by adjuvant chemoradiotherapy for EHC. Among these, 144 patients experienced a recurrence and were included for further analysis. ResultsThe median PROS was 7 months (range, 1–130). In multivariate analysis, poorly differentiated histology, short disease-free survival, poor performance status, and elevated CA 19-9 were identified as significant prognosticators for poor PROS. Based on this, we stratified study patients into three categories by the number of risk factors: group 1 (0 or 1 factors), group 2 (2 factors) and group 3 (3–4 factors). Median PROS for groups 1, 2, and 3 were 13, 7, and 5 months, respectively (p < 0.001). Group 1 patients showed a significant benefit from salvage treatment, but groups 2 and 3 did not demonstrate clear benefit. In addition, we developed a nomogram to specifically identify individual patient's prognosis. ConclusionOur simple risk stratification as well as proposed nomogram can classify patients into subgroups with different prognosis and will help facilitate personalized strategies after recurrence.

Nomogram for predicting survival of postcystectomy recurrent urothelial carcinoma of the bladder

PurposeWe aimed to identify prognostic clinicopathological factors and to create a nomogram able to predict overall survival (OS) in recurrent urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC). Materials and methodsAmong 1,087 patients with UCB who had undergone RC at our 11 institutions between 1990 and 2010, 306 patients who subsequently developed distant metastasis or local recurrence or both were identified. Clinical data were collected with medical record review. Univariate and multivariate Cox regression models addressed OS after recurrence. A nomogram predicting postrecurrence OS was constructed based on Cox proportional hazards model, without using postrecurrence factors (systemic chemotherapy and resection of metastasis). The performance of the nomogram was internally validated by assessing concordance index and calibration plots. ResultsOf the 306 patients, 268 died during follow-up with a median survival of 7 months (95% CI: 5.8–8.5). Postrecurrence chemotherapy was administered in 119 patients (38.9%). Multivariable analysis identified 9 independent predictors for OS; period of time from RC to recurrence (time-to-recurrence), symptomatic recurrence, liver metastasis, hemoglobin level, serum alkaline phosphatase level, serum lactate dehydrogenase level, serum C-reactive protein level, postrecurrence chemotherapy, and resection of metastasis. A nomogram was formed with the following 5 variables to predict OS: time-to-recurrence, symptomatic recurrence, liver metastasis, albumin level, and alkaline phosphatase level. Concordance index rate was 0.75 (95% CI: 0.72–0.78) by internal validation using Bootstraps with 1,000 resamples. Calibration plots showed that the nomogram fitted well. ConclusionsWe identified 9 clinicopathological factors as independent OS predictors in postcystectomy recurrence of UCB. We also created a validated nomogram with 5 variables that efficiently stratified those patients regardless of eligibility for chemotherapy. The nomogram would be useful for acquiring relevant prognostic information and for stratifying patients for clinical trials.

Impact of Systemic Therapy and Recurrence Pattern on Survival Outcome after Radiofrequency Ablation for Colorectal Liver Metastases.

Background: Most patients undergoing radiofrequency ablation (RFA) of colorectal liver metastasases (CLM) develop disease recurrence, but little is known about the effect of recurrence patterns and/or systemic therapy on outcome. In this study, we examined the recurrence patterns and survival after systemic therapy plus RFA in patients with unresectable CLM without extrahepatic disease. The aims were to analyze the effect of recurrence patterns on survival and to assess the relative benefit contributed by systemic therapy and local ablation to disease control and patient outcome.Methods: From January 2002 to December 2012, 113 patients underwent RFA of liver-limited CLM after systemic therapy. Univariate and multivariate analyses for associations between clinical and/or treatment-related variables, recurrence-free survival (RFS), recurrence patterns, and overall survival (OS) were carried out.Results: Of 113 patients, 105 (92.8%) had disease recurrence (median RFS: 6.1 months). Lower post-recurrence OS was observed after early (≤6 months) than after late recurrence (8.5 versus 24.0 months, p < 0.001). Recurrence sites were RFA-sites only (4.8%), liver-only (57.1%), lung-only (10.5%), or multiple (27.6%); the corresponding post-recurrence OS was 21, 19, 39, and 7 months (p < 0.001), respectively. Response to pre-RFA systemic therapy was the strongest predictor for OS (hazard ratio [HR] 5.28), RFS (HR 3.30), early (odds ratio [OR] 6.34) and multiple-site recurrence (OR 3.83) (p < 0.01), respectively; only responders achieved 5-year OS and RFS (29% and 12% versus 0% and 0% for non-responders, p < 0.001, respectively).Conclusions: Survival after RFA for liver-limited CLM is strongly linked to the timing and pattern of non-local disease recurrence. Local ablation efficacy is necessary but not sufficient to obtain long-term disease control. Effective pre-RFA systemic therapy does favourably affect the incidence, timing and patterns of recurrence and long-term survival and appears essential for the tailoring of RFA application to maximize patient benefit.