Significant Factors For Progression-free Survival Research Articles

Five-Year Survival Outcomes After Carbon-Ion Radiotherapy for Operable Stage I NSCLC: A Japanese National Registry Study (J-CROS-LUNG)

IntroductionThe standard therapy for stage I NSCLC is surgery, but some operable patients refuse this option and instead undergo radiotherapy. Carbon-ion radiotherapy (CIRT) is a type of radiotherapy. The Japanese prospective nationwide registry study on CIRT began in 2016. Here, we analyzed real-world clinical outcomes of CIRT for operable patients with stage I NSCLC. MethodsAll patients with operable stage I NSCLC treated with CIRT in Japan between 2016 and 2018 were enrolled. The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology. CIRT was delivered to the primary tumor, not to lymph nodes. ResultsThe median follow-up period was 56 months. Among 136 patients, 117 (86%) had clinical stage IA NSCLC and 19 (14%) had clinical stage IB NSCLC. There were 50 patients (37%) diagnosed clinically without having been diagnosed histologically. Most tumors (97%) were located in the periphery. The 5-year overall survival, cause-specific survival, progression-free survival, and local control rate were 81.8% (95% confidence interval [CI]: 75.1–89.2), 91.2% (95% CI: 86.0–96.8), 65.9% (95% CI: 58.2–74.6), and 95.8% (95% CI: 92.3–99.5), respectively. Multivariate analysis identified age as a significant factor for overall survival (p = 0.018), whereas age and consolidation/tumor ratio (p = 0.010 and p = 0.004) were significant factors for progression-free survival. There was no grade 4 or higher toxicity. Grade 3 radiation pneumonitis occurred in one patient. ConclusionsThis study reports the long-term outcomes of CIRT for operable NSCLC in the real world. CIRT for operable patients has been found to have favorable outcomes, with tolerable toxicity.

Efficacy and Safety of Local Radiotherapy Combined with Chemotherapy ± Bevacizumab in the Treatment of Patients with Advanced and Recurrent Metastatic Cervical Cancer

To observe the efficacy and safety of local radiotherapy combined with chemotherapy ± bevacizumab in the treatment of patients with advanced or recurrent metastatic cervical cancer. A total of 53 patients with advanced and recurrent metastatic cervical cancer who had received local radiotherapy combined with chemotherapy ± bevacizumab in Affiliated Cancer Hospital of Guizhou Medical University from July 2018 to October 2021 were collected. The recurrence types included 21 patients of pelvic recurrence, 7 patients of distant metastasis, 14 patients of complex pelvic recurrence and distant metastasis, and 11 patients of advanced stage (initial diagnosis stage IVB). The primary endpoints were objective response rate (ORR) and disease control rate (DCR). The secondary endpoints were progression-free survival (PFS), overall survival (OS) and incidence of adverse reactions. (1) Complete response (CR) was achieved in 4 patients (7.5%), partial response (PR) in 34 patients (64.2%), stable disease (SD) in 12 patients (22.6%), and disease progression (PD) in 3 patients (5.7%), ORR was 71.7%, DCR was 94.3%. (2) The follow-up time was 5.3 to 45.7 months, the median OS was 29.3 months, the median PFS was 15.7 months, the one-year and two-year OS were 83.0% and 59.2%, and the 1-year and two-year PFS were 62.2% and 34.4%. (3) Recurrence type, tumor size at the time of recurrence, and efficacy after radiotherapy were significant factors for PFS and OS rates in multivariate analysis. (4) The main adverse reactions were myelosuppression, gastrointestinal reaction and urinary reaction. Grade IV leukopenia occurred at 13.2%, grade IV neutropenia at 11.3%, grade IV thrombocytopenia at 15.1%, and grade IV anemia at 5.7%, all of which were tolerable. The gastrointestinal and urinary reactions were mainly grade I-II, and the incidence of vesical or rectovaginal fistulas was about 7.5% (2 patients had rectovaginal fistulas and 2 patients had vesto-vaginal fistulas). Local radiotherapy combined with chemotherapy ± bevacizumab can improve the efficacy and survival of patients with advanced and recurrent metastatic cervical cancer. Adverse reactions are tolerable and may provide survival benefits in these patients.

Population Pharmacokinetics and Exposure-Response Analysis of Tremelimumab 300mg Single Dose Combined with Durvalumab 1500mg Q4W (STRIDE) in Patients with Unresectable Hepatocellular Carcinoma.

A novel single-dose regimen of 300mg tremelimumab in combination with durvalumab (STRIDE) has demonstrated a favorable benefit-risk profile in the phase1/2 Study22 trial (in patients with unresectable hepatocellular carcinoma, uHCC) and in the phase3 HIMALAYA study. The current analysis evaluated the population pharmacokinetics (PopPK) of tremelimumab and durvalumab, and the exposure-response (ER) relationship for efficacy and safety of STRIDE in patients with uHCC. Previous PopPK models for tremelimumab and durvalumab were updated using data from previous studies in various cancers combined with data from Study22 and HIMALAYA. Typical population mean parameters and associated inter- and intra-individual variability were assessed, as was the influence of covariates. Individual exposure metrics were derived from the individual empirical Bayes estimates as drivers for ER analysis related to efficacy and safety from HIMALAYA. The observed pharmacokinetics of tremelimumab in uHCC were well described by a 2-compartment model with both linear and time-dependent clearance. All identified covariates changed tremelimumab PK parameters by <25%, and thus had minimal clinical relevance; similar results were obtained from durvalumab PopPK analysis. None of tremelimumab or durvalumab exposure metrics were significantly associated with overall survival (OS), progression-free survival (PFS), or adverse events. Baseline aspartate aminotransferase and neutrophil-to-lymphocyte ratio (NLR) were associated with OS (P<.001) by the Cox proportional hazards model. No covariate was identified as a significant factor for PFS. No dose adjustment for tremelimumab or durvalumab is needed based on PopPK covariate analyses or ER analyses. Our findings support the novel STRIDE dosing regimen in patients with uHCC.

Stem Cell Autograft Minimal Residual Disease Negativity Improves Outcomes after Autotransplant for Multiple Myeloma

Background: Autologous hematopoietic stem cell transplantation (AHCT) in the up-front setting is the standard-of-care for newly diagnosed multiple myeloma (NDMM). Contemporary induction regimens generate deeper responses, with higher rates of minimal residual disease (MRD) negativity in the bone marrow (BM) leading to improved progression-free survival (PFS) and overall survival (OS). However, it is unclear whether stem cell autograft (AG) contamination with myeloma cells and/or their precursors contributes to relapse after AHCT. To address this, we examined MM contamination of AG by next-generation flow cytometry (NGF) to determine the predictive value of AG MRD status on outcomes after AHCT. Methods: This study included 119 NDMM patients with prospectively collected BM and AG MRD results by NGF who underwent stem cell collection and up-front AHCT at our institution between Sept 2017 and Feb 2020. AG MRD status was assessed in peripheral blood at the time of stem cell collection (SCC). BM MRD status was assessed post-induction/pre-SCC and at 3-months post-AHCT. Additional BM MRD results were also available at 1- and 2-years post-AHCT for most patients. Patients were dichotomized based on AG MRD status (negative vs positive). A Kaplan-Meier model compared median PFS and OS between cohorts. A cox proportional hazards model determined prognostic impact, adjusting for high-risk cytogenetics by FISH and induction therapy. Results: Baseline characteristics were balanced between the MRD-negative and positive groups, with median age at AHCT of 61 (range, 55-67) years in the MRD-negative group and 60 (range, 54-67) years in the MRD-positive group. Patients received a median of 6 (range, 2-12) induction cycles with daratumumab, carfilzomib, lenalidomide, and dexamethasone (D-KRd, n=20), KRd (n=38), bortezomib, lenalidomide, and dexamethasone (VRD, n=51), or other therapy (n=10). Patients with MRD-positive AG were not enriched for high-risk cytogenetics. AG MRD-negativity rates after D-KRd, KRd, VRd, and other therapy were 95.0%, 78.9%, 58.8%, and 50%, respectively. All patients with MRD-positive AG (n=35) also had MRD-positive pre-AHCT BM, whereas 71% of patients with MRD-negative AG had MRD-positive pre-AHCT BM (p <0.001). Sustained or conversion to MRD-negativity in the BM at 3-months and 1-year post-AHCT was observed more for patients with MRD-negative AG than MRD-positive AG (40% vs 9%). At a median follow-up of 40 months (range 33- 46) after AHCT, patients with MRD-negative AG, compared with MRD-positive AG counterparts, had a significantly improved PFS (3-y PFS 78%, CI: 69 ‒ 87, vs. 54%, CI: 39 ‒ 73, p=0.021)(Fig1A) and trend toward better OS (3-y OS 96%, CI: 92 ‒ 100, vs. 82%, CI: 70 ‒ 96)(Fig1B) . The 3-year PFS of the MRD-negative AG group treated with D-KRd, KRd, VRd, and other therapy were 84% (CI: 69 ‒ 100), 79% (CI: 65 ‒ 96), 76% (CI: 71 ‒ 98), and 60% (CI:29 ‒ 100), respectively, while for the MRD-positive AG group treated with KRd, VRd, and other therapy (no D-KRd in this group), 3-year PFS rates were 73% (CI: 47 ‒ 100), 57% (CI: 39 ‒ 83), and 20% (CI:3.5 ‒ 100), respectively (p = 0.4). The 3-year PFS for patients with or without high-risk cytogenetics were 59% (CI: 44 ‒79) and 90% (CI: 81 ‒ 100), respectively, in the MRD-negative AG group, and 40% (CI: 22 ‒ 74) and 67% (CI: 49 ‒ 93), respectively, in the MRD-positive AG group (p = 0.002). The 3-year OS rates were 93% (CI: 85 ‒ 100) and 100% (CI: 100 ‒ 100) for the MRD-negative AG group and 76% (CI: 61 ‒ 100) and 84% (CI: 69 ‒ 100) for the MRD-positive group (p not calculated). On univariate analysis of PFS, the presence of high-risk cytogenetics (HR 3.2, CI: 1.55 ‒ 6.57), R-ISS stage (HR 3.01, CI 1.42 ‒6.41 for R-ISS=3), and AG MRD positive (HR 2.14, CI: 1.10 ‒ 4.16) were significant prognostic factors. Multivariate analysis identified high-risk cytogenetics (HR 3.16, CI: 1.51 ‒ 6.60) as the only significant factor for PFS. Conclusion: Patients with MRD-negative AG have improved PFS and OS following AHCT. These findings support the potential utility of AG MRD status as a prognostic parameter for clinical outcomes, with implications for guiding post-AHCT therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Correlation of BRCA and HRD status with clinical and survival outcomes in patients with advanced-stage ovarian cancer in the age of PARPi maintenance therapy (187)

Objectives: Fifty percent of patients with high-grade ovarian cancer (HGOC) have a germline or somatic (tumor) mutation in BRCA1/BRCA2 or are women who have tumors that do not have a somatic mutation but are classified as homologous recombination deficient (HRD). Current studies suggest that patients with HGOC who are germline BRCA+ (gBRCA) or somatic BRCA (sBRCA)/HRD+ will have a favorable response to poly (ADP-ribose) polymerase inhibitors (PARPi). We aimed to compare clinical and survival outcomes of women with HGOC stratified by germline BRCA or somatic BRCA/HRD status and evaluate the impact of PARPi maintenance therapy. Methods: We performed a retrospective analysis of all patients with advanced HGOC from April 2013 to March 2021. Patients were included if germline BRCA and HRD status were known. Clinical outcomes were analyzed and stratified by (1) gBRCA+ (2) gBRCA - and sBRCA/HRD+, or (3) BRCA-/HRD-. Progression-free survival (PFS) was estimated using Kaplan-Meier methods stratified by HRD status and modeled via Cox proportional hazards regression. Results: A total of 1,124 patients were reviewed, and 352 met our inclusion criteria. The Median follow-up was 27.3 months. One hundred and thirty-nine patients had gBRCA+ mutation, 69 sBRCA+/ HRD+, and 143 BRCA-/HRD-. Patients with BRCA-/HRD- tumors had older median age (64 vs 54 and 62 years, p<0.001) and lower median CA-125 at diagnosis (423 vs 832 and 857 U/ml, p=0.002), were more likely of White race (87% vs 76% and 66%, p=0.008), required more median NACT cycles (4 vs 3 and 3 cycles, p=0.03), were more likely to have surgically unresectable disease at diagnosis (52% vs 35% and 46%, p=0.02), and were less likely to get PARPi frontline maintenance therapy (7% vs 17% and 25%, p=0.001). Twenty-nine patients (8%) received PARPi frontline, and 51 patients (14%) received PARPi maintenance therapy at recurrence. Patients with BRCA-/HRD- disease had worse PFS (16.9 months vs 25 and 25.2 months, p<0.001) than those with gBRCA+ and sBRCA+/HRD+ disease. Multivariate analysis for PFS revealed that age (HR: 1.02, 95% CI: 1.00-1.03, p=0.04), stage III, IV (HR: 5.02, 95% CI: 1.21-20.94, p=0.03), complete gross resection at tumor reductive surgery (HR: 0.40, 95% CI: 0.23-0.69, p=0.004), and BRCA-/HRD- status (HR: 1.74, 95% CI: 1.20-2.51, p=0.004) were significant factors for PFS. The 6-month and 12-month survival probabilities of patients on frontline PARPi maintenance therapy were 1.00 (95% CI: NE) and 0.82 (0.59-0.93), respectively, regardless of gBRCA+ or sBRCA+/HRD+ status. Objectives: Fifty percent of patients with high-grade ovarian cancer (HGOC) have a germline or somatic (tumor) mutation in BRCA1/BRCA2 or are women who have tumors that do not have a somatic mutation but are classified as homologous recombination deficient (HRD). Current studies suggest that patients with HGOC who are germline BRCA+ (gBRCA) or somatic BRCA (sBRCA)/HRD+ will have a favorable response to poly (ADP-ribose) polymerase inhibitors (PARPi). We aimed to compare clinical and survival outcomes of women with HGOC stratified by germline BRCA or somatic BRCA/HRD status and evaluate the impact of PARPi maintenance therapy. Methods: We performed a retrospective analysis of all patients with advanced HGOC from April 2013 to March 2021. Patients were included if germline BRCA and HRD status were known. Clinical outcomes were analyzed and stratified by (1) gBRCA+ (2) gBRCA - and sBRCA/HRD+, or (3) BRCA-/HRD-. Progression-free survival (PFS) was estimated using Kaplan-Meier methods stratified by HRD status and modeled via Cox proportional hazards regression. Results: A total of 1,124 patients were reviewed, and 352 met our inclusion criteria. The Median follow-up was 27.3 months. One hundred and thirty-nine patients had gBRCA+ mutation, 69 sBRCA+/ HRD+, and 143 BRCA-/HRD-. Patients with BRCA-/HRD- tumors had older median age (64 vs 54 and 62 years, p<0.001) and lower median CA-125 at diagnosis (423 vs 832 and 857 U/ml, p=0.002), were more likely of White race (87% vs 76% and 66%, p=0.008), required more median NACT cycles (4 vs 3 and 3 cycles, p=0.03), were more likely to have surgically unresectable disease at diagnosis (52% vs 35% and 46%, p=0.02), and were less likely to get PARPi frontline maintenance therapy (7% vs 17% and 25%, p=0.001). Twenty-nine patients (8%) received PARPi frontline, and 51 patients (14%) received PARPi maintenance therapy at recurrence. Patients with BRCA-/HRD- disease had worse PFS (16.9 months vs 25 and 25.2 months, p<0.001) than those with gBRCA+ and sBRCA+/HRD+ disease. Multivariate analysis for PFS revealed that age (HR: 1.02, 95% CI: 1.00-1.03, p=0.04), stage III, IV (HR: 5.02, 95% CI: 1.21-20.94, p=0.03), complete gross resection at tumor reductive surgery (HR: 0.40, 95% CI: 0.23-0.69, p=0.004), and BRCA-/HRD- status (HR: 1.74, 95% CI: 1.20-2.51, p=0.004) were significant factors for PFS. The 6-month and 12-month survival probabilities of patients on frontline PARPi maintenance therapy were 1.00 (95% CI: NE) and 0.82 (0.59-0.93), respectively, regardless of gBRCA+ or sBRCA+/HRD+ status.

Diffuse Large B-Cell Lymphoma in the Elderly : Retrospective Analysis from a Single Tertiary Cancer Center in India

IntroductionDiffuse large B-cell lymphoma (DLBCL) commonly affects the elderly population and the treatment is often challenging because of the close interplay between age, comorbidities, frailty as well as cognitive and psychosocial factors. Anthracycline constitutes the cornerstone of the treatment regimen of Non-Hodgkin lymphoma but is associated with several side-effects including cardiotoxicity. At our institute, we replace doxorubicin with etoposide in cases where compromised cardiac function, performance status (PS) and multiple comorbidities are major concerns. We aim to retrospectively analyze the treatment outcomes of patients with DLBCL aged ≥ 60 years and specifically compare R-CHOP and R-CEOP regimens.MethodsIn this retrospective study, we included patients aged ≥ 60 years, newly diagnosed with DLBCL according to WHO classification between January 2015 to December 2018 at our center. Chemotherapy regimens received included R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone), R-CE (Etoposide) OP for anthracycline-ineligible or elderly frail patients and R-EPOCH, followed by radiotherapy for residual disease or bulky sites (size > 7cm). The decision to use anthracycline or non-anthracycline based regimen was at the discretion of the physician depending on the performance status, frailty and serum albumin levels. Dose of etoposide used in the R-CEOP regimen was 65mg/m 2 orally on day 1-3. Primary G-CSF prophylaxis was used in all patients. After 4 cycles of chemotherapy, patients underwent an interim PET-CT for response evaluation. Patients who attained partial response underwent a repeat PET-CT evaluation at the end of 6 cycles. Post treatment completion, patients were followed up for clinical examination every three months for the first two years, six monthly for the next three years and annually thereafter.ResultsA total of 218 patients were included. The median age of patients was 65 years (range, 60-88 years). Patients were divided into two age-groups with 124 patients (56.9%) of the age group of 60-65 years and 94 patients (43.1%) were aged above 65 years. Of the 218 patients, 71 patients (32.6%) received R-CHOP regimen and 137 patients (62.4%) received R-CEOP regimen, while 10 patients (5.0%) received R-EPOCH. More patients aged >65 years received R-CEOP than in the 60-65 years age group (83% vs 47.6%) and the difference was statistically significant (p-value <0.001). Reasons for replacing doxorubicin were cardiac contraindications (9.6%), presence of hypertension or ≥ 2 significant comorbidities (29.9%), advanced age (age ≥ 75 years, 8.0%), baseline Eastern Cooperative Oncology Group (ECOG) PS of > 2 (3.6%), and physician's discretion in 48.9% of cases. Baseline disease characteristics including NCCN-IPI of patients treated with both these regimens were comparable. Complete response rate and overall response rate were higher in the R-CHOP group compared to the R-CEOP group, but statistically significant difference was found only among 60-65 years of age group. Among patients aged 60-65 years, the incidence of febrile neutropenia and grade III/IV hematological toxicities were significantly higher in the R-CHOP group than in the R-CEOP group. The overall median follow-up was 22.71 months (Range 1-81 months). The 2-year progression-free survival (PFS) rate in the R-CHOP group was higher than that in the R-CEOP group (79.1% vs 49.6%, p-value <0.001) (Figure 1). This statistically higher 2-year PFS rate was found among patients with early as well as advanced stage disease, and also in the age group of 60-65 years (Figure 2, 3). Match pairing analysis after adjusting for confounders like NCCN-IPI and presence of bulky disease showed significantly higher 2-year PFS rate in the R-CHOP group than in the R-CEOP group (70.0% vs 34.6%, p-value <0.001). ECOG PS at presentation, NCCN-IPI and the chemotherapy regimen were found to be significant factors for PFS by multivariate analysis (Table 1).ConclusionAge and comorbidities are not absolute contraindications to the use of anthracyclines. Fit patients without cardiac contraindications should receive R-CHOP regimen whenever possible. Geriatric assessment tools should be used for the frail or unfit patients to guide appropriate therapy and further prospective trials should be done in this direction. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Genomic Instability of Circulating Tumor DNA as a Prognostic Marker for Pancreatic Cancer Survival: A Prospective Cohort Study.

Simple SummaryThis prospective cohort study showed that circulating tumor DNA-genomic instability (ctDNA-GI) I-scores, which was defined as the natural logarithm of the sum of LOESS-normalized Z-scores of sequenced reads in 1 Mb bins, are prognostic of the outcome of either localized or metastatic pancreatic adenocarcinoma. At baseline, 24.1% of patients had high genomic instability with I-score. Multivariable analyses demonstrated I-score was a significant factor for progression-free survival and overall survival.Genomic instability of circulating tumor DNA (ctDNA) as a prognostic biomarker has not been evaluated in pancreatic cancer. We investigated the role of the genomic instability index of ctDNA in pancreatic ductal adenocarcinoma (PDAC). We prospectively enrolled 315 patients newly diagnosed with resectable (n = 110), locally advanced (n = 78), and metastatic (n = 127) PDAC from March 2015 through January 2020. Low-depth whole-genome cell-free DNA sequencing identified genome-wide copy number alterations using instability score (I-score) to reflect genome-wide instability. Plasma cell-free and matched tumor tissue DNA from 15 patients with resectable pancreatic cancer was sequenced to assess the concordance of chromosomal copy number alteration profiles. Associations of I-score with clinical factors or survival were assessed. Seventy-six patients had high genomic instability with I-score > 7.3 in pre-treatment ctDNA; proportions of high I-score were 5.5%, 5.1%, and 52% in resectable, locally advanced, and metastatic stages, respectively. Correlation coefficients between Z-scores of plasma and tissue DNA at segment resolution were high (r2 = 0.82). Univariable analysis showed the association of I-score with progression-free survival in each stage. Multivariable analyses demonstrated that clinical stage-adjusted I-scores were significant factors for progression-free and overall survival. In these patients, ctDNA genomic I-scores provided prognostic information relevant to progression-free survival in each clinical stage.

Efficacy of Icotinib, an EGFR Tyrosine Kinase Inhibitor in Non-Small Cell Lung Cancer Patients with Exon 19 Deletion and Exon 21 L858R: A Retrospective Analysis in China

Introduction: The effect of icotinib on non-small cell lung cancer (NSCLC) patients with EGFR exon 19 deletions (19-Del) or L858R point mutation in exon 21 (21-L858R) remains inconsistent. This study aimed to evaluate the efficacy and safety of icotinib in patients with advanced NSCLC harboring these 2 EGFR mutations. Methods: We retrospectively assessed the clinical effects of first-line icotinib on advanced NSCLC patients with 2 classic EGFR mutations. Kinase activity assays were used to reaffirm the preclinical efficacy. Results: Among 2,757 patients, 2,365 (86%) harbored 19-Del (1,346/2,757, 49%) or 21-L858R (1,019/2,757, 37%) mutation. Patients with 19-Del had a higher response rate (ORR; 67.8 vs. 62.1%; p = 0.0039) and disease control rate (98.5 vs. 97.2%; p = 0.0223) than those with 21-L858R mutation. The median progression-free survival (PFS) in the 19-Del group (22.3 months, 95% confidence interval [CI]: 21.3–23.4) was significantly longer than that in the 21-L858R group (20.4 months, 95% CI: 19.5–21.7) (p = 0.004). In multivariate analysis, mutation types, clinical stage, and smoking history were significant factors for PFS. Additionally, an in vitro study indicated the 50% inhibitory concentrations (IC₅₀) of icotinib was lower for EGFR 19-Del than 21-L858R. Conclusion: These results suggest that EGFR 19-Del confers superior PFS and response to the icotinib treatment compared to 21-L858R.

Significance of liver metastasis volume in breast cancer patients treated with stereotactic body radiotherapy.

This study analyzed the impact of liver metastasis (LM) volume on treatment outcomes in breast cancer (BC) patients treated with stereotactic body radiotherapy (SBRT). This single-institution retrospective analysis included 40oligometastatic (≤ 5 metastases) BC patients with 58liver metastases treated with SBRT between April 2013 and March 2021. The prognostic factors for local control (LC), overall survival (OS), and progression-free survival (PFS) rates were assessed. Median follow-up time was 28.1months. Isolated and solitary LM were seen in26 (65%) and24 (60%) patients, respectively. Median time to disease recurrence was 10.7months post liver SBRT. The 2‑year OS, PFS, and LC rates were 71.4%, 27.5%, and 86.8%, respectively. In univariate analysis, patients with agross tumor volume (GTV) of ≤ 6cc and aplanning target volume (PTV) of ≤ 38cc demonstrated asignificantly better median OS than those with GTV > 6cc and PTV > 38cc. In multivariate analysis, the predictive factors for worse OS were GTV > 6cc (HR = 3.07 [95% CI, 1.14-8.22; p = 0.03]) and PTV > 38 cc (HR = 5.91 [95% CI, 1.92-18.21; p = 0.002]). No significant factor for PFS was found. Only 2patients experienced rib fracture at 4and 6months post treatment, and 1patient had agradeII duodenal ulcer. Liver SBRT is an effective and safe treatment option for oligometastatic BC patients with excellent LC, promising survival, and limited toxicity. Patients with smaller tumors displayed better OS than their counterparts, validating the effectiveness of alocal treatment for this group.

Radiation Therapy for Grade 3 Gliomas: Correlation of MRI Findings With Prognosis.

Background and objectivePostoperative radiotherapy is usually indicated for both grade 3 glioma and grade 4 glioblastoma. However, the treatment results and tumor features of grade 3 glioma clearly differ from those of glioblastoma. There is limited information on outcomes and tumor progression for grade 3 glioma. In this study, we evaluate the result of postoperative radiotherapy for grade 3 glioma and focus on the correlation of MRI findings with prognosis.MethodsIn this study, 99 of 110 patients with grade 3 glioma who received postoperative radiotherapy and were followed up for more than one year were retrospectively analyzed. The total irradiation dose was 60.0 Gy in 30 fractions, and daily temozolomide or two cycles of nimustine (ACNU) was concurrently administered during radiotherapy. The median follow-up period was 46 months (range: 2-151 months).ResultsIn multivariate analysis, pathology [anaplastic oligodendroglioma (AO) vs. anaplastic astrocytoma (AA)], the status of surgical resection (biopsy vs. partial resection or more), and contrast enhancement (enhanced by MRI image or not) were significant factors for overall survival (OS). The five-year OS for AO vs. AA cases were 76.8% vs. 46.1%, total to partial resection vs. biopsy cases were 72.7% vs. 21.0%, and non-enhanced vs. enhanced cases were 82.5% vs. 45.6%, respectively. In multivariate analysis, the status of surgical resection and longer extension of preoperative edema (PE) were significant factors for progression-free survival (PFS). The five-year PFS for the total to partial resection vs. biopsy cases were 52.9% vs. 10.7%, and non-extensive PE vs. extensive PE (EPE) cases were 62.2% vs. 19.1%, respectively.ConclusionOur results suggest that a contrast-enhanced tumor on MRI and a longer PE may also be significantly associated with OS and PFS among grade 3 glioma patients.

Impact of loco-regional treatment including radiotherapy in patients presenting with metastatic breast cancer

AbstractBackground:The impact of loco-regional treatment (LRT) with radiotherapy (RT) in patients presenting with metastatic breast cancer (MBC) has not been widely studied. The aim of this study was to review the treatment outcomes of LRT including RT in patients with MBC.Materials and methods:Patients who presented with MBC were included in this retrospective study. Analysis was undertaken to determine the difference in local disease control, overall survival (OS) and progression-free survival (PFS) with systemic treatment alone, surgery alone, surgery plus RT and RT alone with long-rank test. Multivariate analysis was done, using the cox regression for factors affecting PFS and OS.Results:From 2007 to 2014, data of 257 patients with MBC were collected. Totally, 185 patients received LRT and 72 did not. LRT was surgery plus RT, surgery only and RT only in 113, 47 and 25 patients, respectively. Cytotoxic chemotherapy and hormone therapy were received by 205 and 166 patients, respectively. Median follow-up was 36 months (6–120 months). PFS and OS at 3 years with and without LRT were 31% versus 6% (p &lt; 0·001) and 41% versus 17% (p &lt; 0·001), respectively. PFS at 3 years with surgery plus RT, RT alone and surgery was 40, 33 and 6%, respectively. OS at 3 years with surgery plus RT, RT alone and surgery was 50, 38 and 17%, respectively. Patients without LRT had worse PFS and OS, 6 and 17%, respectively. RT had significant impact on PFS and OS along with chemotherapy and hormone treatment.Conclusion:In patients with MBC, improved local control, PFS and OS were achieved with loco-regional RT. Loco-regional RT along with chemotherapy and hormones were significant factors for PFS and OS irrespective of surgery.

Efficacy and Safety of Lenvatinib-Transcatheter Arterial Chemoembolization Sequential Therapy for Patients with Intermediate-Stage Hepatocellular Carcinoma

Introduction: We evaluated the efficacy and safety of lenvatinib-transcatheter arterial chemoembolization (LEN-TACE) sequential therapy for patients (n = 88) with intermediate-stage hepatocellular carcinoma (HCC). Methods: Eighty-eight patients who obtained tumor control by LEN treatment were analyzed; 30 received LEN followed by TACE (LEN-TACE sequential therapy), and 58 received LEN monotherapy. Propensity score matching was performed, and the outcomes of 19 patients in the LEN-TACE group and 19 patients in the LEN-alone group were compared. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and change in albumin-bilirubin (ALBI) score were evaluated. Results: After matching, baseline characteristics were similar between the groups. The ORR was 63.2% with LEN-TACE group and 63.2% with the LEN-alone group. Multivariate analysis showed that addition of TACE during LEN treatment (hazard ratio [HR] 0.264, 95% confidence interval [CI] 0.087–0.802, p = 0.019) and Child-Pugh score 5 (HR 0.223, 95% CI 0.070–0.704, p = 0.011) were the significant factors for PFS. Median PFS was 11.6 months with LEN-TACE and 10.1 months with LEN-alone. The survival rate of the LEN-TACE group was significantly higher than that of the LEN-alone group (median survival time; not reached vs. 16.9 months, p = 0.007). The incidence of common LEN-associated AEs was similar between groups. Although elevated aspartate aminotransferase/alanine aminotransferase and fever were more frequent with LEN-TACE group, these events were manageable. Conclusion: For patients with intermediate-stage HCC, LEN-TACE sequential therapy may provide a deep response and favorable prognosis.

Impact of sarcopenia on survival of pancreatic cancer patients treated with concurrent chemoradiotherapy.

To investigate the prognostic impact of sarcopenia on the survival of patients with locally advanced pancreatic cancer (LAPC) treated with concurrent chemoradiotherapy (CCRT). We retrospectively reviewed 299 patients diagnosed with LAPC and treated with definitive CCRT from 2000 to 2015. Skeletal muscle index (SMI) was measured using computed tomography scans and sarcopenia was defined as SMI <29.6 cm2/m2 for women and <36.2 cm2/m2 for men. The significance of sarcopenia for progression-free survival (PFS) and overall survival (OS) was evaluated. Sarcopenia was present in 29 patients (9.7%). In multivariate analysis, sarcopenia was a significant factor for PFS (p = 0.043). Although sarcopenia was not a significant factor for OS (p = 0.121) in multivariate analysis, long-term survivors were observed only in the no sarcopenia group (OS at 60 months: 9.5% vs 0%, p < 0.001). In patients undergoing CCRT for LAPC, sarcopenia is an independent factor for adverse prognosis.

Survival and Prognostic Factors for Breast Cancer Patients with Regional Oligo-Recurrence.

PurposeThis study aimed to evaluate survival outcomes and identify prognostic factors for regional oligo-recurrence in breast cancer patients who received salvage local treatment.MethodsIn the breast cancer registry of our institution, 18,790 patients received curative surgery for stage I–III breast cancer between January 1995 and June 2016. Of those patients, only 87 (0.5%)underwent salvage local treatment for isolated nodal recurrence on the axillary lymph nodes (ALNs) (n = 58), supraclavicular lymph nodes (SCNs) (n = 17), or internal mammary lymph nodes (IMNs) (n = 12).ResultsThe median follow-up duration after regional oligo-recurrence was 49 months (range: 6–194 months). For patients with recurrence of ALN, SCN, or IMN, the 5-year progression-free survival (PFS) and overall survival (OS) rates were 40.0%, 32.1%, and 25.0%, respectively (p = 0.3) and 62.7%, 70.0%, and 58.3%, respectively(p = 0.97). In the multivariable analysis for PFS, age at recurrence ≥ 65 years, disease-free interval < 24 months, non-luminal A subtype, and in-field failure (marginally significant) were found to be risk factors (RFs). However, the location of the tumor was not a significant factor for PFS (p = 0.71). When we stratified patients by the number of RFs, the 5-year PFS rates were 67.5% for patients with ≤ 1 RF and 7.3% for those with > 1 RF (p < 0.01). For patients with ≤ 1 RF, the 5-year PFS rates were 73.5% in the ALN group and 51.1% in the SCN/IMN group (p = 0.09). For patients with > 1 RF, the 5-year PFS rates were 7.3% in the ALN group and 7.1% in the SCN/IMN group (p = 1.00).ConclusionIn breast cancer patients with regional oligo-recurrence, clinical outcomes after salvage treatment were favorable in patients with ≤ 1 RF, while patients with > 1 RF had poor prognoses irrespective of the location of recurrence.

RTHP-09. SINGLE INSTITUTION’S EXPERIENCE FOR PEDIATRIC INTRACRANIAL EPENDYMOMA TREATED WITH ADJUVANT RADIOTHERAPY

Abstract PURPOSE To investigate long term outcomes of pediatric intracranial ependymoma treated with maximal safe resection followed by radiotherapy in single institution. METHODS Between 1983 and 2016, 42 pediatric patients received adjuvant radiotherapy after surgery. There were 19 and 23 grade II and III ependymomas, and total resection could be performed in 50% of patients. There were 4 patients with initial leptomeningeal seeding, and craniospinal irradiation (CSI) was the component of adjuvant treatment in 5 patients including them. Local radiotherapy (median 54 Gy (range, 45–60 Gy) was performed in all the rest patients excluding three with whole-brain radiotherapy. RESULTS With a median follow-up of 89 months, 14 patients (33%) experienced recurrences after radiotherapy (m/c: intracranial, 79%, all within tumor bed). The 5- and 10-year progression-free survival (PFS) rates were 70% and 63%, and overall survival (OS) rates were 85% and 78%, respectively. The recurrence rates were significantly higher in patients younger than 3 years (64% vs. 23%, p = 0.024) or with subtotal resection (STR) (52% vs. 15%, p = 0.009). In multivariate analyses, age and STR were significant factors for PFS (p = 0.007 and 0.028, respectively). There was no independent prognostic factor for OS on multi-variate analysis. Fourteen patients experienced recurrence. Among them, all of 6 grade II cases showed local recurrence. Four grade II cases (67%) underwent aggressively salvage treatments such as resection, stereotactic radiosurgery were still under observation. However, 75% of 8 grade III recurrent cases were expired, despite aggressive salvage treatments. All 3 patients with seeding recurrent were grade III and died from disease. CONCLUSION Local adjuvant radiotherapy showed favorable survival in pediatric ependymoma. Even if recurrence occurs, aggressive salvage treatment would be needed for grade II ependymoma.

Predictive biomarkers for the efficacy of nivolumab as ≥ third-line therapy in patients with advanced gastric cancer (AGC): From a subset analysis of ATTRACTION-2 phase III trial.

152 Background: ATTRACTION-2 phase III trial proved the clinical efficacy of nivolumab (Nivo) in AGC patients (pts) treated with ≥ 2 previous chemotherapy regimens. However, the benefits of Nivo seem to be limited to a subset of pts and there is a need to identify predictive markers to select pts who would benefit from Nivo. Methods: Clinical data and tumor samples of AGC pts enrolled from Asan Medical Center in ATTRACTION-2 study were retrospectively analyzed. PD-L1 (+) was defined as combined positive score of ≥ 1%. EBV and MSI status were determined by EBV-encoded small RNA in situ hybridization and IHC for MLH-1, MSH-2, PMS-2, and MSH-6, respectively. Tumor mutation burden (TMB) was acquired by targeted next-generation sequencing using the NextSeq platform with OncoPanel. Results: A total of 45 pts (28/17 in Nivo/placebo arms) were eligible for the analysis. Baseline neutrophil-lymphocyte ratio (NLR) was median 2.9 and 7 pts had hyponatremia ( &lt; 135). In 36 pts with available tissues, there were PD-L1 (+) (N = 13, 36.1%), EBV (+) (N = 6, 16.7%), and no MSI-high. TMB data could be acquired in 29 pts and median TMB was 8.2/Mb (0.0-21.3). With a median follow-up of 28.3 months (mo) in surviving pts, objective response rate, median progression-free survival (PFS), and overall survival (OS) were 16.7%, 1.6 mo, and 8.1 mo in Nivo arm and 0%, 1.6 mo and 6.5 mo in placebo arm. In Nivo arm with measurable lesions, PD-L1 (+) pts had significantly higher disease control rate than PD-L1 (-) pts (87.5% vs. 20%, p = 0.015). In multivariate model adjusted for important factors (age, sex, Nivo vs. placebo, treatment line, NLR, Na, and PD-L1), NLR ≤ 2.9 and PD-L1 (+) were significant factors for PFS (Hazard Ratio [HR] 0.47, p = 0.037 and HR 0.32, p = 0.006, respectively) and PD-L1 (+) was a significant factor for OS (HR, 0.44, p = 0.012). With adjusting these factors with TMB, PD-L1 (+) remained favorable for PFS and OS. Pts with NLR ≤ 2.9 or PD-L1 (+) or Na &gt; 135 significantly favored Nivo compared to placebo in terms of PFS and OS. Conclusions: Baseline NLR and PD-L1 status may be relevant predictive markers to select pts with AGC who would benefit from Nivo.

Cannabis Impacts Tumor Response Rate to Nivolumab in Patients with Advanced Malignancies.

There has been a significant increase in the use of immunotherapy and cannabis recently, two modalities that have immunomodulatory effects and may have possible interaction. We evaluated the influence of cannabis use during immunotherapy treatment on response rate (RR), progression-free survival (PFS), and overall survival (OS). In this retrospective, observational study, data were collected from the files of patients treated with nivolumab in the years 2015-2016 at our hospital, and cannabis from six cannabis-supplying companies. Included were 140 patients (89 nivolumab alone, 51 nivolumab plus cannabis) with advanced melanoma, non-small cell lung cancer, and renal clear cell carcinoma. The groups were homogenous regarding demographic and disease characteristics. A comparison between the two arms was made. In a multivariate model, cannabis was the only significant factor that reduced RR to immunotherapy (37.5% RR in nivolumab alone compared with 15.9% in the nivolumab-cannabis group (p = .016, odds ratio = 3.13, 95% confidence interval 1.24-8.1). Cannabis use was not a significant factor for PFS or OS. Factors affecting PFS and OS were smoking (adjusted hazard ratio [HR] = 2.41 and 2.41, respectively (and brain metastases (adjusted HR = 2.04 and 2.83, respectively). Low performance status (adjusted HR = 2.83) affected OS alone. Tetrahydrocannabinol and cannabidiol percentages did not affect RR in any group (p = .393 and .116, respectively). In this retrospective analysis, the use of cannabis during immunotherapy treatment decreased RR, without affecting PFS or OS and without relation to cannabis composition. Considering the limitations of the study, further prospective clinical study is needed to investigate possible interaction. Although the data are retrospective and a relation to cannabis composition was not detected, this information can be critical for cannabis users and indicates that caution is required when starting immunotherapy.

Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma.

Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad). KRAS mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20-3.63] and KRAS fraction (HR, 1.73; 95% CI, 1.02-2.95) were significant factors for progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05-3.67) also had prognostic implications for overall survival. Subgroup analyses showed that KRAS mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC (P = 0.016). Moreover, when combined with the cancer biomarker CA19-9, the KRAS mutation concentration in cfDNA showed additive benefits for the prediction of overall survival. This study demonstrates that multiplex detection of KRAS mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC.

High-dose radiotherapy with intensity-modulated radiation therapy for advanced hepatocellular carcinoma.

We report the results of intensity-modulated radiotherapy for patients with advanced hepatocellular carcinoma who were not candidate for local ablative therapies, transarterial chemoembolization or hepatic arterial infusion chemotherapy. Between 2003 and 2008, 27 patients were treated with high-dose radiotherapy (median dose, 50.4 Gy). The equivalent sphere size of tumors was 11.4 ± 2.6 cm. Nineteen and 8 patients were Child-Pugh class A and B, respectively. Eighteen patients had thromboses in large veins. Six patients were treated with radiotherapy as the initial treatment modality, and 21 patients received other treatments before radiotherapy. The overall response rate was 44.4% (1 pathologic complete response and 11 partial responses). The primary failure pattern was intrahepatic disease progression. Until the last follow-up, the primary liver masses and vein thromboses did not progress in 63.6% and 60.0% of the patients, respectively. The median progression-free survival and overall survival after radiotherapy rate were 3 and 5 months, respectively. Based on univariate analyses, response, Child-Pugh classification, and vein thrombosis were significant factors for overall survival, and tumor response, tumor size, vein thrombosis, and multiplicity were significant factors for progression-free survival. Tumor response was the only significant prognostic factor for overall survival and progression-free survival based on multivariate analyses. Radiotherapy with intensity-modulated radiotherapy achieved a good response rate in patients with advanced hepatocellular carcinoma, and patients who had a good response lived longer than patients who did not have a good response.

Treatment outcomes of locally advanced squamous cell carcinoma of the maxillary sinus treated with chemoradioselection using superselective intra-arterial cisplatin and concomitant radiation: Implications for prognostic factors

BackgroundThis study clarified the clinical results of locally advanced squamous cell carcinoma of the maxillary sinus (SCC-MS) that was treated with chemoradioselection using superselective intra-arterial cisplatin and concomitant radiation (RADPLAT). Prognostic factors were also investigated. MethodsWe retrospectively analyzed 63 locally advanced SCC-MS patients treated with initial RADPLAT followed by sequential RADPLAT (S-RADPLAT) or surgery. ResultsThe 5-year progression-free survival (PFS) and overall survival (OS) rates of patients with T3, T4a, or T4b disease were 72.2%, 46.6%, and 33.3% (p = 0.104) and 83.3%, 51.6%, and 33.3% (p = 0.031), respectively. The 5-year PFS and OS rates of the S-RADPLAT or surgery groups with T4 disease were 39.6% and 60.6% (p = 0.199) and 44.7% and 63.3% (p = 0.276), respectively. Tumor extension into the medial and/or lateral pterygoid muscle (p < 0.001) and N classification (p = 0.012) were considered significant factors for PFS. Regarding OS, tumor extension into the medial and/or lateral pterygoid muscle (p = 0.005) was considered a statistically significant risk factor. ConclusionsIt may be better for T4 non-responders to initial RADPLAT to undergo surgery. Patients with high risk factors of positive neck metastasis or pterygoid muscle extension may need adjuvant chemotherapy.