Repeat Local Treatment of Recurrent Colorectal Liver Metastases, the Role of Neoadjuvant Chemotherapy: An Amsterdam Colorectal Liver Met Registry (AmCORE) Based Study

This cohort study aimed to evaluate efficacy, safety, and survival outcomes of neoadjuvant chemotherapy (NAC) followed by repeat local treatment compared to upfront repeat local treatment of recurrent colorectal liver metastases (CRLM). A total of 152 patients with 267 tumors from the prospective Amsterdam Colorectal Liver Met Registry (AmCORE) met the inclusion criteria. Two cohorts of patients with recurrent CRLM were compared: patients who received chemotherapy prior to repeat local treatment (32 patients) versus upfront repeat local treatment (120 patients). Data from May 2002 to December 2020 were collected. Results on the primary endpoint overall survival (OS) and secondary endpoints local tumor progression-free survival (LTPFS) and distant progression-free survival (DPFS) were reviewed using the Kaplan–Meier method. Subsequently, uni- and multivariable Cox proportional hazard regression models, accounting for potential confounders, were estimated. Additionally, subgroup analyses, according to patient, initial and repeat local treatment characteristics, were conducted. Procedure-related complications and length of hospital stay were compared using chi-square test and Fisher’s exact test. The 1-, 3-, and 5-year OS from date of diagnosis of recurrent disease was 98.6%, 72.5%, and 47.7% for both cohorts combined. The crude survival analysis did not reveal a significant difference in OS between the two cohorts (p = 0.834), with 1-, 3-, and 5-year OS of 100.0%, 73.2%, and 57.5% for the NAC group and 98.2%, 72.3%, and 45.3% for the upfront repeat local treatment group, respectively. After adjusting for two confounders, comorbidities (p = 0.010) and primary tumor location (p = 0.023), the corrected HR in multivariable analysis was 0.839 (95% CI, 0.416–1.691; p = 0.624). No differences between the two cohorts were found with regards to LTPFS (HR = 0.662; 95% CI, 0.249–1.756; p = 0.407) and DPFS (HR = 0.798; 95% CI, 0.483–1.318; p = 0.378). No heterogeneous treatment effects were detected in subgroup analyses according to patient, disease, and treatment characteristics. No significant difference was found in periprocedural complications (p = 0.843) and median length of hospital stay (p = 0.600) between the two cohorts. Chemotherapy-related toxicity was reported in 46.7% of patients. Adding NAC prior to repeat local treatment did not improve OS, LTPFS, or DPFS, nor did it affect periprocedural morbidity or length of hospital stay. The results of this comparative assessment do not substantiate the routine use of NAC prior to repeat local treatment of CRLM. Because the exact role of NAC (in different subgroups) remains inconclusive, we are currently designing a phase III randomized controlled trial (RCT), COLLISION RELAPSE trial, directly comparing upfront repeat local treatment (control) to neoadjuvant systemic therapy followed by repeat local treatment (intervention).

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Thermal Ablation Compared to Partial Hepatectomy for Recurrent Colorectal Liver Metastases: An Amsterdam Colorectal Liver Met Registry (AmCORE) Based Study

Cancers ◽

10.3390/cancers13112769 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2769

Author(s):

Madelon Dijkstra ◽

Sanne Nieuwenhuizen ◽

Robbert S. Puijk ◽

Florentine E.F. Timmer ◽

Bart Geboers ◽

...

Keyword(s):

Liver Metastases ◽

Hospital Stay ◽

Partial Hepatectomy ◽

Thermal Ablation ◽

Colorectal Liver Metastases ◽

Local Treatment ◽

Length Of Hospital Stay ◽

Progression Free Survival ◽

Free Survival ◽

Subgroup Analyses

The aim of this study was to assess safety, efficacy and survival outcomes of repeat thermal ablation as compared to repeat partial hepatectomy in patients with recurrent colorectal liver metastases (CRLM). This Amsterdam Colorectal Liver Met Registry (AmCORE) based study of two cohorts, repeat thermal ablation versus repeat partial hepatectomy, analyzed 136 patients (100 thermal ablation, 36 partial hepatectomy) and 224 tumors (170 thermal ablation, 54 partial hepatectomy) with recurrent CRLM from May 2002 to December 2020. The primary and secondary endpoints were overall survival (OS), distant progression-free survival (DPFS) and local tumor progression-free survival (LTPFS), estimated using the Kaplan–Meier method, and complications, analyzed using the chi-square test. Multivariable analyses based on Cox proportional hazards model were used to account for potential confounders. In addition, subgroup analyses according to patient, initial and repeat local treatment characteristics were performed. In the crude overall comparison, OS of patients treated with repeat partial hepatectomy was not statistically different from repeat thermal ablation (p = 0.927). Further quantification of OS, after accounting for potential confounders, demonstrated concordant results for repeat local treatment (hazard ratio (HR), 0.986; 95% confidence interval (CI), 0.517–1.881; p = 0.966). The 1-, 3- and 5-year OS were 98.9%, 62.6% and 42.3% respectively for the thermal ablation group and 93.8%, 74.5% and 49.3% for the repeat resection group. No differences in DPFS (p = 0.942), LTPFS (p = 0.397) and complication rate (p = 0.063) were found. Mean length of hospital stay was 2.1 days in the repeat thermal ablation group and 4.8 days in the repeat partial hepatectomy group (p = 0.009). Subgroup analyses identified no heterogeneous treatment effects according to patient, initial and repeat local treatment characteristics. Repeat partial hepatectomy was not statistically different from repeat thermal ablation with regard to OS, DPFS, LTPFS and complications, whereas length of hospital stay favored repeat thermal ablation. Thermal ablation should be considered a valid and potentially less invasive alternative for small-size (0–3 cm) CRLM in the treatment of recurrent new CRLM. While, the eagerly awaited results of the phase III prospective randomized controlled COLLISION trial (NCT03088150) should provide definitive answers regarding surgery versus thermal ablation for CRLM.

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The Role of Neoadjuvant Chemotherapy in Repeat Local Treatment of Recurrent Colorectal Liver Metastases: A Systematic Review and Meta-Analysis

Cancers ◽

10.3390/cancers13030378 ◽

2021 ◽

Vol 13 (3) ◽

pp. 378

Author(s):

Madelon Dijkstra ◽

Sanne Nieuwenhuizen ◽

Robbert S. Puijk ◽

Bart Geboers ◽

Florentine E. F. Timmer ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Liver Metastases ◽

Observational Studies ◽

Colorectal Liver Metastases ◽

Controlled Trial ◽

Meta Analysis ◽

Local Treatment ◽

National Guidelines ◽

Significant Difference

The additive value of neoadjuvant chemotherapy (NAC) prior to repeat local treatment of patients with recurrent colorectal liver metastases (CRLM) is unclear. A systematic search was performed in PubMed, Embase, Web of Science, and an additional search in Google Scholar to find articles comparing repeat local treatment by partial hepatectomy and/or thermal ablation with versus without NAC. The search included randomized trials and comparative observational studies with univariate/multivariate analysis and/or matching as well as (inter)national guidelines assessed using the AGREE II instrument. The search identified 21,832 records; 172 were selected for full-text review; 20 were included: 20 comparative observational studies were evaluated. Literature to evaluate the additive value of NAC prior to repeat local treatment was limited. Outcomes of NAC were often reported as subgroup analyses and reporting of results was frequently unclear. Assessment of the seven studies that qualified for inclusion in the meta-analysis showed conflicting results. Only one study reported a significant difference in overall survival (OS) favoring NAC prior to repeat local treatment. However, further analysis revealed a high risk for residual bias, because only a selected group of chemo-responders qualified for repeat local treatment, disregarding the non-responders who did not qualify. All guidelines that specifically mention recurrent disease (3/3) recommend repeat local treatment; none provide recommendations about the role of NAC. The inconclusive findings of this meta-analysis do not support recommendations to routinely favor NAC prior to repeat local treatment. This emphasizes the need to investigate the additive value of NAC prior to repeat local treatment of patients with recurrent CRLM in a future phase 3 randomized controlled trial (RCT).

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Is there an oligometastatic state in pancreatic cancer? Practical clinical considerations raise the question

British Journal of Radiology ◽

10.1259/bjr.20190627 ◽

2020 ◽

Vol 93 (1106) ◽

pp. 20190627

Author(s):

Marta Scorsetti ◽

Tiziana Comito ◽

Davide Franceschini ◽

Ciro Franzese ◽

Maria Giuseppina Prete ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Pancreatic Adenocarcinoma ◽

Local Treatment ◽

Stage Iv ◽

Progression Free Survival ◽

Free Survival ◽

Number Of Patients ◽

Clinical Considerations

Objectives: To evaluate the role of stereotactic body radiotherapy (SBRT) as a local ablative treatment (LAT) in oligometastatic pancreatic cancer. Methods: Patients affected by histologically confirmed stage IV pancreatic adenocarcinoma were included in this analysis. Endpoints are local control (LC), progression-free survival (PFS), and overall survival (OS). Results: From 2013 to 2017, a total of 41 patients were treated with SBRT on 64 metastases. Most common sites of disease were lung (29.3%) and liver (56.1%). LC at 1 and 2 years were 88.9% (95% CI 73.2–98.6) and 73.9% (95% CI 50–87.5), respectively. Median LC was 39.9 months (95% CI 23.3—not reached). PFS rates at 1 and 2 years were 21.9% (95% CI 10.8–35.4) and 10.9% (95% CI 3.4–23.4), respectively. Median PFS was 5.4 months (95%CI 3.1–11.3). OS rates at 1 and 2 years were 79.9% (95% CI 63.7–89.4) and 46.7% (95% CI 29.6–62.2). Median OS was 23 months (95%CI 14.1–31.8). Conclusions: Our results, although based on a retrospective analysis of a small number of patients, show that patients with oligometastatic pancreatic cancer may benefit from local treatment with SBRT. Larger studies are warranted to confirm these results. Advances in knowledge: Selected patients affected by oligometastatic pancreatic adenocarcinoma can benefit from local ablative approaches, like SBRT

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Cytarabine Either with Induction or Conditioning May Improve Outcomes Among Those Undergoing Autologous Transplantation in First or Second Remission for Mantle Cell Lymphoma

Blood ◽

10.1182/blood.v120.21.4546.4546 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4546-4546

Author(s):

Bijal D. Shah ◽

Bryan J Little ◽

Jennifer Cultrera ◽

Celeste M. Bello ◽

Lubomir Sokol ◽

...

Keyword(s):

Cell Lymphoma ◽

Autologous Transplantation ◽

Conditioning Regimen ◽

Progression Free Survival ◽

Published Data ◽

Free Survival ◽

Improve Outcome ◽

Significant Difference ◽

Mantle Cell

Abstract Abstract 4546 Introduction: Consolidation with autologous transplantation (AutoSCT) may extend progression free survival when administered following initial induction. Published data suggest intensive cytarabine containing induction may improve outcome when administered prior to autologous transplantation. Methods: We retrospectively evaluated all patients with MCL transplanted at our institution before 2010. We identified 57 patients, among whom 52 were transplanted in first or second remission. Results: 21 patients had received a cytarabine containing induction (most commonly R-HyperCVAD), among whom 14 also received cytarabine as a component of conditioning (BEAM+/−R). The most common induction in the remaining patients was R-CHOP. Among the 31 who did not receive a cytarabine based induction, 23 received cytarabine as a component of the pre-transplant conditioning regimen (BEAM+/−R). The median PFS for those getting cytarbine with induction and conditioning was approximately 28 months (at which time 51% of patients continued without progression). The median PFS for those getting cytarabine with conditioning only was approximately 38 months (at which time 47% continued without progression). Logrank analysis shows no statistically significant difference between these groups (p one-sided = 0.29). Alternatively, those who did not receive any cytarabine had a median PFS of 20 months, with no survival beyond 33 months. Logrank analysis shows this to be inferior to those receiving cytarabine with induction/conditioning (p one-sided = 0.049), as well as among those who received cytarabine with conditioning only (p one-sided = 0.001). Conclusions: In the absence of randomized comparisons it is difficult to draw firm conclusions on the role of induction. These analyses would suggest that among those with chemosensitive disease able to proceed to transplant, more modern conditioning with cytarabine containing regimens may make up for lack of exposure to this agent during induction. Disclosures: Sokol: Celgene: Honoraria, Speakers Bureau.

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Role of Lymphadenectomy During Interval Debulking Surgery Performed After Neoadjuvant Chemotherapy in Patients With Advanced Ovarian Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.646135 ◽

2021 ◽

Vol 11 ◽

Author(s):

Minjun He ◽

Yuerong Lai ◽

Hongyu Peng ◽

Chongjie Tong

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Progression Free Survival ◽

Debulking Surgery ◽

Hazard Ratios ◽

Significant Difference ◽

Interval Debulking Surgery

ObjectiveThe role of lymphadenectomy in interval debulking surgery (IDS) performed after neoadjuvant chemotherapy (NACT) in advanced ovarian cancer remains unclear. We aimed to investigate the clinical significance of lymphadenectomy in IDS.MethodsWe retrospectively reviewed and analyzed the data of patients with advanced ovarian cancer who underwent NACT followed by IDS.ResultsIn 303 patients receiving NACT-IDS, lymphadenectomy was performed in 127 (41.9%) patients. One hundred and sixty-three (53.8%) patients achieved no gross residual disease (NGRD), and 69 (22.8%) had residual disease < 1 cm, whereas 71 (23.4%) had residual disease ≥ 1cm. No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between the lymphadenectomy group and the no lymphadenectomy group in patients with NGRD, residual disease < 1 cm, and residual disease ≥ 1 cm, respectively. The proportions of pelvic, para-aortic and distant lymph node recurrence were 7.9% (10/127), 4.7% (6/127) and 5.5% (7/127) in the lymphadenectomy group, compared with 5.7% (10/176, P = 0.448), 4.5% (8/176, P = 0.942) and 5.1% (9/176, P = 0.878), respectively, in no lymphadenectomy group. Multivariate analysis identified residual disease ≥ 1 cm [hazard ratios (HR), 4.094; P = 0.008] and elevated CA125 levels after 3 cycles of adjuvant chemotherapy (HR, 2.883; P = 0.004) were negative predictors for OS.ConclusionLymphadenectomy may have no therapeutic value in patients with advanced ovarian cancer underwent NACT-IDS. Our findings may help to better the therapeutic strategy for advanced ovarian cancer. More clinical trials are warranted to further clarify the real role of lymphadenectomy in IDS.

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Efficacy and safety of radiotherapy (RT) plus temozolomide (TMZ) in elderly patients (EP) with glioblastoma (GBM).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.2043 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 2043-2043 ◽

Cited By ~ 1

Author(s):

Giuseppe Lombardi ◽

Luisa Bellu ◽

Franco Berti ◽

Patrizia Farina ◽

Sara Galuppo ◽

...

Keyword(s):

Haematological Toxicity ◽

Progression Free Survival ◽

Severe Toxicity ◽

Wild Type ◽

Free Survival ◽

Kaplan Meier ◽

Significant Difference ◽

Grade 3 ◽

Ecog Ps

2043 Background: the optimal management of EP with GBM remains controversial. The role of RT with TMZ for EP is unclear, and EP are often treated with RT alone, TMZ alone or palliative approaches. We describe our experience of combining RT with concurrent TMZ for treatment of EP with GBM Methods: medical records of patients ≥65 years old with newly GBM, histologically confirmed at Veneto Institute of Oncology – Padua, and treated with RT plus TMZ, were reviewed. Concomitant TMZ was 75mg/m2/die. The adjuvant treatment consisted of TMZ 150-200mg/m2/die for six cycles. Median progression-free survival(PFS) and overall survival(OS) were estimated with Kaplan-Meier method. Toxicity was scored according to CTCAE 4.0 Results: we analyzed 60 patients(PTS), 34 males and 26 females; the average age was 70 (range 65-82); ECOG PS was 0-1 in 35 PTS and 2 in 25 PTS; complete surgery was performed in 35 PTS, partial surgery in 25 PTS. 40 and 20 PTS received RT within 6 or more weeks (range 7-9) from surgery. MGMT and IDH1 were analyzed in 43 PTS: MGMT methylated in 20 PTS (46%), all PTS had wild-type IDH1. 34 PTS were treated with RT 40Gy in 15 fractions, 26 PTS with RT 60Gy in 30 fractions with no significant difference in ECOG PS, MGMT and type of surgery between the two subgroups. For all PTS, PFS and OS were 9.5 and 12.7 ms, respectively. OS was 13.7 and 12.4 ms (p=0.9) in PTS receiving RT within 6 or more weeks from surgery, respectively. 13% of PTS showed grade 3-4 haematological toxicity, 12% grade 3-4 asthenia, 3% nausea/vomiting. MGMT methylated and complete surgery was associated with a longer survival. PFS was 9 vs 10 months (p=0.4) and OS was 11.7 vs 13.7 ms (p=0.1), for PTS treated with 40Gy and 60Gy, respectively. Regarding toxicity: grade 3-4 haematological toxicity was 9% vs 23%, severe asthenia was 9% vs 15%, nausea/vomiting was 3% vs 4% of PTS receiving RT 40Gy and 60Gy, respectively. Conclusions: RT plus TMZ is effective and safe in EP with GBM and good ECOG PS. PFS and OS was not statistically different between PTS receiving RT 40Gy or 60Gy, although we showed a trend for longer OS with RT 60Gy; in contrast, severe toxicity was higher in PTS with RT 60Gy. OS was similar between PTS receiving RT within 6 or more weeks (7-9ws) from surgery.

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Association of PD-L1 expression with tumor infiltrating immune cells and mutation burden in the high grade neuroendocrine carcinoma of the lung.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.8564 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 8564-8564 ◽

Cited By ~ 2

Author(s):

Hye Sook Kim ◽

Ji-Youn Han

Keyword(s):

Neuroendocrine Carcinoma ◽

Immune Cells ◽

Progression Free Survival ◽

Large Cell ◽

High Grade ◽

Free Survival ◽

Mutation Burden ◽

Programmed Death ◽

Significant Difference

8564 Background: Large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are recognized as high grade neuroendocrine carcinoma of the lung and remain among the most fatal malignancies. Programmed death-ligand 1 (PD-L1) is expressed in a group of cancers that may be suitable for specific immunotherapy. We retrospectively investigated PD-L1 expression in tumor cells (TC) and tumor infiltrating immune cells (IC) and correlated this with mutation burden and clinical outcome. Methods: A total of 192 patients with LCNEC (n = 72) and SCLC (n = 120) were explored. PD-L1 expression was scored by immunohistochemistry in TC and IC. We used the Ion AmpliSeq Comprehensive Cancer Panel to identify mutation in all exons in 409 cancer-related genes. Results: The overall prevalence of PD-L1 expression on TC was 15.1 % (29/192). No significant difference was observed between LCNEC and SCLC (16.7% vs. 14.2%, p = 0.365). Tumor-infiltrating IC and PD-L1 positive immune cells (IC) were observed in 34.4% (66/192) and 31.3% (60/192), respectively. The prevalence of tumor-infiltrating IC and PD-L1 expression on IC were significantly higher in LCNEC compared to SCLC (57.6% vs. 23.3%, p < .001; 45.8% vs. 22.5%, p = .001, respectively). Tumor-infiltrating IC and PD-L1 expression on IC were correlated with higher nonsynonymous mutational load (p = 0.048 and 0.038, respectively). Tumor-infiltrating immune cells (median 11.3 vs. 6.8 months, p = 0.005), and its correlated PD-L1 expression on IC (median 11.3 vs. 7.0 months, p = 0.024) were related with better progression free survival. There was no relevance between biomarker status and overall survival. Conclusions: These findings suggest that the PD-1/PD-L1 pathway is activated in a fraction of HGNEC of lung with correlating higher mutational burden. Further studies are needed to determine the PD-L1 expression and correlated clinical features to refine role of anti-PD1 treatments in these patient population.

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Autologous Transplantation in Relapsed and Refractory Mantle Cell Lymphoma

Blood ◽

10.1182/blood.v120.21.4542.4542 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4542-4542

Author(s):

Bijal D. Shah ◽

Bryan J Little ◽

Jennifer Cultrera ◽

Celeste M. Bello ◽

Lubomir Sokol ◽

...

Keyword(s):

Autologous Transplantation ◽

Progression Free Survival ◽

Refractory Disease ◽

Limited Data ◽

Free Survival ◽

Significant Difference ◽

Mantle Cell ◽

First Remission ◽

First Relapse

Abstract Abstract 4542 Introduction: Consolidation with autologous transplantation (AutoSCT) may extend progression free survival when administered following initial induction. There are limited data to support the role of AutoSCT in the relapsed or refractory setting. Methods: We retrospectively evaluated all patients with MCL transplanted at our institution before 2010. We identified 57 patients, among whom 42 were transplanted in first remission (CR1, n=32; PR1 n=10), 11 in second remission (CR2, n=4, PR2, n=7), and 4 with relapsed/refractory disease beyond first remission. Results: The median PFS are: CR1 37mo, PR1 24mo, CR2 not reached, and PR2 23mo. No statistically significant difference was observed between patients transplanted CR1 vs PR1 (p one-sided =0.08), CR2 vs PR2 (p one-sided =0.10), or in CR/PR1 vs CR/PR2 (p one-sided =0.39). The median PFS for those with refractory disease, and/or those transplanted beyond second remission was 6mo which is significantly inferior to the cohort of those transplanted in first or second remission (p one-sided =.01). The median OS calculated from transplant are: CR1 63mo, PR1 50mo, CR2 not reached, PR2 45mo. No statistically significant difference was observed between patients transplanted CR1 vs PR1 (p one-sided =0.47), CR2 vs PR2 (p one-sided =0.46), or in CR/PR1 vs CR/PR2 (p one-sided =0.29). The median OS for those with refractory disease, and/or those transplanted beyond second remission was 16mo which is not statistically significantly inferior to the cohort of those transplanted in first or second remission (p one-sided =.067). MIPI data collected at diagnosis were available for 30 patients, all transplanted in first or second remission with chemosensitive disease. These data were not predictive of survival or progression from transplantation. Simplified MIPI obtained at the time of transplant were available for 44 patients, all transplanted in first or second remission with chemosensitive disease. These data were similarly uninformative for prediction of progression or survival from transplantation. Conclusions: Consolidation with AutoSCT may be similarly effective for patients in first relapse with chemosensitive disease. MIPI at diagnosis and the simplified MIPI at transplant may failed to account for survival among highly selected patients considered eligible for transplantation. Disclosures: Sokol: Celgene: Honoraria, Speakers Bureau.

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Examining the Use of Radiation Therapy for Cholangiocarcinoma: Benefits through Modern Techniques

Oncology Research and Treatment ◽

10.1159/000517533 ◽

2021 ◽

pp. 1-6

Author(s):

Michael Oertel ◽

Felix Gattermann ◽

Hartmut Schmidt ◽

Hans Theodor Eich

Keyword(s):

Radiation Therapy ◽

Local Control ◽

Progression Free Survival ◽

Free Survival ◽

Treatment Situation ◽

Significant Difference ◽

Bile Duct Epithelium ◽

Definitive Surgery

Background: Cholangiocarcinoma (CCA) is a rare malignant tumor of the bile duct epithelium. At first diagnosis, only a minority of patients are eligible for surgery, which is regarded as the only curative treatment. This study examines the role of radiation therapy (RT) and chemoradiotherapy (CRT) in the definitive and adjuvant treatment situation. Methods: The monocentric, retrospective analysis included 39 patients with CCA undergoing 53 RT courses. Data were collected from January 2005 to September 2018. There were 11 cases of CRT, 6 of which were definitive. Surgery was either palliative (n = 6) or radical (n = 15). Results: After RT, the median overall survival (OS) was 10.4 months (m), median progression-free survival was 5.6 m, and median duration of local control (DOLC) was 8.9 m. There was a significant difference in survival between patients with and without locoregional lymph node metastasis (OS: 4.3 vs. 15.4 m, p = 0.031). After treatment of a primary tumor, DOLC was about twice as long as in the recurrent situation (10.4 vs. 5.4 m, p = 0.032). Conservative therapy significantly elevated the risk of local recurrence compared to radical surgery in univariate and multivariate analyses. Side effects were mostly classified as mild to moderate. Termination of RT and increased alanine aminotransferase were significantly less frequent after stereotactic body radiation therapy and hypofractionation. Conclusion: RT can achieve local control in patients with CCA. Toxicities of RT are manageable but require close clinical and laboratory follow-up.

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The role of subgroup analyses: results from the NOVA trial

Cancer Breaking News ◽

10.19156/cbn.2017.0039 ◽

2017 ◽

Vol 5 (1) ◽

pp. 40-42

Author(s):

Massimo Di Maio ◽

Alice Bergamini

Keyword(s):

Ovarian Cancer ◽

Maintenance Treatment ◽

Progression Free Survival ◽

Adenosine Diphosphate ◽

Parp Inhibitors ◽

Wild Type ◽

Free Survival ◽

Platinum Sensitive ◽

Subgroup Analyses

The clinical efficacy of poly-adenosine diphosphate (ADP) ribose polymerase (PARP) inhibitors in BRCA-mutated ovarian cancer patients has been widely reported. However, novel challenges are currently aimed at broadening the benefit of PARP inhibitors to patients with wild-type BRCA and homologous recombination deficiency (HRD) and identifying a test able to select those patients who might benefit most from this therapy. The recently published ENGOT-OV16/NOVA trial reported an advantage in progression-free survival (PFS) for patients receiving the PARP1/2 inhibitor niraparib, as maintenance treatment for platinum-sensitive ovarian cancer compared to placebo, regardless of their germline BRCA or HRD status. This suggests that niraparib could potentially represent a valuable maintenance option for virtually all patients with platinum-sensitive relapsed ovarian cancer and that the HRD assay used in this trial is not able to reliably identify those patients who benefit the most from niraparib maintenance. These provocative considerations are the result of subgroup analyses that should be interpreted with caution but are useful to show the consistency of the effect of niraparib across the whole population.

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