Distant Metastasis-free Survival Rates Research Articles

Volumetric PET Parameters Predict Prognosis after Definitive Chemoradiotherapy with Cisplatin/Docetaxel for Stage III Non-Small Cell Lung Cancer.

The aim of this study was to investigate whether volumetric positron emission tomography (PET) parameters are prognostic predictors in stage III non-small cell lung cancer patients receiving definitive concurrent chemo-radiotherapy (CCRT) with cisplatin/docetaxel. Cases involving definitive CCRT were reviewed retrospectively, and the maximum standardized uptake value, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated. The relationships between these PET parameters and prognosis were analyzed. MTV and TLG were significant predictors of distant metastasis-free survival (DMFS) (p = 0.0003 and 0.0005, respectively) and progression-free survival (PFS) (p = 0.001 and 0.0007, respectively). The three-year DMFS rates in patients with low and high MTV were 13.3% and 64.6%, respectively, and the corresponding values in those with low and high TLG were 13.3% and 65.2%, respectively. The three-year PFS rates in patients with low and high MTV were 13.3% and 57.8%, respectively, and the corresponding values in patients with low and high TLG were 13.3% and 57.8%, respectively. However, MTV and TLG were not predictors of local control or overall sur-vival. We demonstrated that volumetric PET parameters were predictors of patients receiving definitive CCRT. Our findings contradict the findings of previous reports and warrant further research to validate them.

Stereotactic Body Radiotherapy for High-Risk Localized Carcinoma of the Prostate (SHARP) Consortium: Analysis of 344 Prospectively Treated Patients

To explore the efficacy and toxicity of stereotactic body radiation therapy (SBRT) in high-risk prostate cancer (HRPCa) in a consortium of 7 institutional phase 2 trials and prospective registries. Individual patient data were pooled for 344 patients with a minimum follow-up of 24 months. Biochemical recurrence-free survival (BCRFS) and distant metastasis-free survival (DMFS) were estimated using a Kaplan-Meier framework. Fine and Gray competing risk and Cox proportional hazards regression models were developed to assess the association between time to BCR and time to distant metastasis and prespecified variables of interest. Logistic regression models were developed to evaluate associations between acute and late grade ≥2 genitourinary and gastrointestinal and the following a priori-specified variables: age, dose per fraction, ADT use, and nodal radiation therapy. Median follow-up was 49.5 months. Seventy-two percent of patients received ADT, with a median duration of 9 months, and 19% received elective nodal radiation therapy. Estimated 4-year BCRFS and DMFS rates were 81.7% (95% CI, 77.2%-86.5%) and 89.1% (95% CI, 85.3%-93.1%). The crude incidences of late grade ≥3 genitourinary and gastrointestinal toxicity were 2.3% and 0.9%. These data support a favorable toxicity and efficacy profile for SBRT for HRPCa. Further prospective studies are needed to evaluate the optimal dose and target volume in the context of SBRT for HRPCa.

Locoregional recurrence following nipple-sparing mastectomy with immediate breast reconstruction: Patterns and prognostic significance

IntroductionThere are limited available data on the prognostic implications of locoregional recurrence (LRR) after nipple-sparing mastectomy (NSM) and immediate reconstruction. In this study, we investigated the patterns and prognosis associated with LRR following this treatment approach for breast cancer. MethodsA total of 1696 patients with primary breast cancer who underwent NSM with immediate reconstruction from March 2003 to December 2016 were retrospectively analyzed. Post-recurrence disease-free survival (DFS) and distant metastasis-free survival (DMFS) rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate analyses using the Cox proportional hazards model were performed to evaluate the prognostic factors associated with the DFS and DMFS. ResultsAfter a median follow-up period of 84 months, we identified 172 patients (10.1%) with an LRR as the first event. The 5-year post-recurrence DFS rates for the nipple-areola complex recurrence (NCR), skin or subcutaneous recurrence/chest wall recurrence (SCR/CWR), and regional recurrence (RR) groups were 89.1%, 73%, and 59.4%, respectively (P = 0.009), and the 5-year post-recurrence DMFS rates for the NCR, SCR/CWR, and RR groups were 96%, 82.8%, and 59.7%, respectively (P < 0.001). In multivariate analysis, a time to LRR ≤2 years (P = 0.016) and the site of LRR (P = 0.022) were significantly associated with the post-recurrence DFS. ConclusionsNCR is more likely to be detected as a non-invasive recurrence and is associated with more favorable overall outcomes than other LRR types. The interval to LRR and its site of onset seem to be associated with the prognostic outcomes.

Long-Term MINDACT Results Affirm Excellent Prognosis for Clinically and Genetically Low-Risk Early Breast Cancer.

The 8-year distant metastasis-free survival rate is 94.7% for patients with clinically and genetically low-risk early breast cancer who forgo adjuvant chemotherapy, according to updated findings from the phase III MINDACT trial.

Clinical value of docetaxel plus cisplatin (TP) induction chemotherapy followed by TP concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma.

Objective: To investigate the clinical value of induction chemotherapy (IC) with docetaxel plus cisplatin (TP) followed by concurrent chemoradiotherapy (CCRT) with TP in locoregionally advanced nasopharyngeal carcinoma (NPC).Methods: A total of 544 patients with locoregionally advanced NPC that was newly diagnosed from January 2009 to December 2015 were included in this study. Among these patients, 251 were treated with TP induction chemotherapy followed by CCRT with cisplatin (DDP) alone (TP + DDP group), 167 were treated with TP followed by CCRT with TP (TP + TP group), and 126 were treated with docetaxel, DDP and fluorouracil (TPF) followed by CCRT with DDP alone (TPF + DDP group). Overall survival (OS), distant metastasis-free survival (DMFS), progression-free survival (PFS) and locoregional relapse-free survival (LRRFS) were analyzed using the Kaplan-Meier method and a Cox proportional hazards model.Results: Survival analysis showed that the 5-year OS, PFS and DMFS rates in the TP + DDP group were significantly lower than those in the TP + TP group after propensity score matching (PSM). Multivariate analysis revealed that CCRT with TP was an independent prognostic factor for OS, PFS and DMFS. During CCRT, the incidence rates of grade 3/4 nausea/vomiting, oral mucositis, leukocytopenia and neutropenia were significantly increased in the TP + TP group compared with the TP + DDP group (all P < 0.05). To further explore the value of TP + TP, we performed PSM again with the TPF + DDP group. After PSM, there were 100 patients in each group. Survival analysis showed no significant differences in the 5-year OS, PFS, DMFS and LRRFS rates between the two groups. During IC and CCRT, the rate of grade 3/4 nausea/vomiting in the TPF + DDP group was higher than that in the TP+TP group (9.0% vs. 2.0%, P = 0.030; 18.0% vs. 8.0%, P = 0.036, respectively). No significant difference in the incidence of grade 3/4 hematologic toxicity was found between the two groups (all P > 0.05).Conclusion: TP + TP can reduce the distant metastasis of locoregionally advanced NPC and improve OS compared with TP + DDP; TP + TP has the same effect as TPF + DDP and is clinically feasible.

Significance of serum CA125 level in surgically resected cervical adenocarcinoma with adverse features.

ObjectiveUnlike cervical squamous cell carcinoma, there are no consensus criteria for serum tumor markers in cervical adenocarcinoma. This study aimed to identify the prognostic value of preoperative carbohydrate antigen 125 (CA125) levels in cervical adenocarcinoma patients with adverse pathologic features.MethodsA total of 105 patients who underwent radical hysterectomy followed by adjuvant radiotherapy (RT) or concurrent chemoradiation therapy were included. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were evaluated using the Cox proportional hazard regression model.ResultsUsing a cutoff value of 50 U/mL, 83 and 22 patients had low- and high-CA125, respectively. Patients with high-CA125 had a larger tumor size, more frequent parametrial extension, and more frequent lymph node metastasis than those with low-CA125. During a median follow-up of 59.3 (interquartile range, 32.7–97.8) months, patients with high-CA125 showed inferior 5-year LRFS, DMFS, and OS rates compared to those with low-CA125 (38.5% vs. 70.0%; 37.0% vs. 69.4%; 43.6% vs. 78.1%, respectively, all p<0.05). In multivariable analysis, the high-CA125 remained significant prognostic factor for LRFS, DMFS, and OS (all p<0.05). Furthermore, 12 patients with high-CA125 at recurrence exhibited lower 5-year OS rates than 21 patients with low-CA125 at recurrence (0.0% vs. 51.3%, p=0.003).ConclusionIn this retrospective analysis, the serum CA125 level at diagnosis and recurrence was related to the extent of disease and prognosis of cervical adenocarcinoma with adverse pathologic features. A CA125 level of ≥50 U/mL may be a prognostic surrogate marker for cervical adenocarcinoma in patients with the presence of adverse factors.

Impact of p53, HIF1a, Ki-67, CA-9, and GLUT1 Expression on Treatment Outcomes in Locally Advanced Cervical Cancer Patients Treated With Definitive Chemoradiation Therapy

The objective of this study was to assess the association between pretreatment p53, hypoxia inducible factor 1a (HIF1a), Ki-67, carbonic anhydrase-9 (CA-9), and glucose transporter 1 (GLUT1) expression in locally advanced cervical cancer patients treated definitively with concurrent chemoradiation therapy (CRT) and treatment outcomes including overall survival (OS), progression-free survival (PFS), local-regional control (LC), and distant metastases-free survival (DMFS). Twenty-eight patients treated definitively and consecutively for cervical cancer with CRT had p53, HIF1a, Ki-67, CA-9, and GLUT1 protein expression assessed and scored semiquantitatively by 3 pathologists, blinded to the treatment outcomes. Outcomes were stratified by p53 (H-score: <15 vs. ≥15), HIF1a (H-score: <95 vs. ≥95), Ki-67 (labeling index <41% vs. ≥41%), CA-9 (H-score: <15 vs. ≥15), and GLUT1 (H-score: <175 vs. ≥175) expression. OS, PFS, LC, and DMFS rates were calculated using the Kaplan-Meier method, and differences between groups were evaluated by the log-rank test. Notable clinical characteristics of the cohort included median age of 51 years (range: 32 to 74 y), FIGO stage IIB disease (57.2%), clinical node-negative disease (64.3%), squamous cell carcinoma (89.3%), and adenocarcinoma (10.7%). Treatment outcomes included 5-year OS (57.2%), PFS (48.1%), LC (72.1%), and DMFS (62.9%). For HIF1a H-score <95 and ≥95, the 5-year OS (52.0% and 68.4%, P=0.58), PFS (53.0% and 40.9%, P=0.75), LC (71.6% and 68.2%, P=0.92), and DMFS (59.7% and 52.0%, P=0.91) were not significantly different. For Ki-67 labeling index <41% and ≥41%, the 5-year OS (44.9% and 66.6%, P=0.35), PFS (38.9% and 55.4%, P=0.53), LC (57.7% and 85.7%, P=0.22), and DMFS (67.3% and 61.0%, P=0.94) were not significantly different. For CA-9 H-score <15 and ≥15, the 5-year OS (54.4% and 66.7%, P=0.39), PFS (57.3% and 40.0%, P=0.87), LC (70.0% and 70.0%, P=0.95), and DMFS (70.0% and 46.7%, P=0.94) were not significantly different. For GLUT1 H-score <175 and ≥175, the 5-year OS (43.6% and 43.6%, P=0.32), PFS (55.6% and 49.5%, P=0.72), LC (72.9% and 71.5%, P=0.97), and DMFS (62.5% and 59.6%, P=0.76) were not significantly different. For p53, H-score <15 and ≥15, the 5-year OS (62% and 53%), PFS (63% and 30.3%), LC (87.5% and 52%), and DMFS (79.6% and 41.6%). In this study population, HIF1a, Ki-67, CA-9, and GLUT1 expression did not predict treatment response or outcomes in locally advanced cervical cancer patients treated definitively with CRT. There was a nonstatistically significant trend towards worse outcomes with p53 expression.

Postoperative radiotherapy for patients with completely resected pathological stage IIIA-N2 non-small cell lung cancer: a preferential benefit for squamous cell carcinoma.

BackgroundThe beneficial effect of postoperative radiotherapy (PORT) on completely resected pathological IIIA-N2 (pIIIA-N2) non-small cell lung cancer (NSCLC) has been a subject of interest with controversy. The aim of the study was to distinguish the clinical efficacy of PORT on lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC) among pIIIA-N2 NSCLC.Patients and methodsBetween October 2010 and September 2016, 288 consecutive patients with completely resected pIIIA-N2 NSCLC at Beijing Chest Hospital were retrospectively analyzed, which consisted of 194 cases of LADC and 85 cases of LSCC. There were 42 (21.6%) patients treated with PORT in LADC cases and 19 (22.3%) patients treated with PORT in LSCC cases. The 5-year overall survival (OS), loco-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS) were calculated using the Kaplan-Meier method. The prognostic factors were determined using Cox’s regression model.ResultsAmong 194 cases of LADC, the 1-, 3-, and 5-year OS in the PORT group were 95.2%, 61.9% and 40.0%, respectively, while in the non-PORT group were 90.1%, 63.3% and 45.0% (p = 0.948). The use of postoperative chemotherapy (POCT) and smoking index ≥ 400 were both prognostic factors of 5-year rates of OS, LRFS and DMFS. On the other hand, among 85 cases of LSCC, the 1-, 3-, and 5-year OS in the PORT group were 94.7%, 63.2% and 63.2%, respectively, whereas in the non-PORT group were 86.4%, 48.5% and 37.1% (p = 0.026). In this group, only the use of PORT was a favorable prognostic factor for 5-year OS, LRFS and DMFS.ConclusionsDue to clinicopathological differences among completely resected pIIIA-N2 NSCLC, PORT may not be suitable to all patients. Our study distinguishes pIIIA-N2 LSCC from LADC by their positive responses to PORT.

Radical Hemithoracic Radiotherapy Versus Palliative Radiotherapy in Non-metastatic Malignant Pleural Mesothelioma: Results from a Phase 3 Randomized Clinical Trial

Purpose We conducted a phase 3 randomized clinical trial to assess whether radical hemithoracic radiation therapy (RHR) compared with palliative radiation therapy (PR) can achieve overall survival (OS) advantages in patients with malignant pleural mesothelioma (MPM). Methods and Materials From August 2014 to May 2018, patients with histologically diagnosed nonmetastatic MPM, who underwent nonradical lung-sparing surgery and chemotherapy (CHT), were randomly assigned (1:1) to receive RHR or PR. RHR total dose to the involved pleural cavity was 50 Gy in 25 fractions, and the gross residual disease received a simultaneous integrated boost of 60 Gy. The primary endpoint was OS. Secondary endpoints were local control, distant metastasis-free survival, progression-free survival, and acute and late toxicity rates. A sample size of 108 patients considering a type I error (α) of 0.05 and a statistical power of 80% was calculated to prove that RHR could improve the 2-year OS. OS was estimated with the Kaplan-Meier method and the log-rank test (2-sided) tested differences between arms. The univariate and multivariate analyses were performed using Cox proportional hazard model. Possible prognostic factors investigated: age, sex, performance status, lung surgery, gross residual disease, and histology. Results One hundred eight patients were randomized: 53 to the PR arm and 55 to the RHR arm. Median follow-up was 14.6 months. The 2-year OS rate was 58% in the RHR arm versus 28% in the PR arm (hazard ratio, 0.54; 95% confidence interval, 0.31-0.95; P = .031). In the RHR arm: 11 patients experienced acute toxicity grade ≥3, 17 patients had grade 3 to 4 late toxicity. Nine patients experience a grade ≥2 pneumonitis, including 1 patient with grade 5. Conclusions RHR significantly improves survival in patients with MPM treated with nonradical lung-sparing surgery and CHT compared with palliative treatments, although it is associated with a nonnegligible toxicity profile.

Hypofractionated intensity-modulated radiotherapy with concurrent chemotherapy for elderly patients with locally advanced pancreatic carcinoma

BackgroundIt is important to understand how elderly patients with locally advanced pancreatic carcinoma (LAPC) should be treated, since the number of elderly cancer patients will increase. However, the optimal treatment for elderly patients with LAPC remains unclear. The purpose of this study was to evaluate the efficacy and safety of hypofractionated intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine for elderly patients with LAPC.MethodsWe retrospectively analysed the data from LAPC patients aged ≥ 75 years treated with hypofractionated IMRT (48 Gy in 15 fractions) with concurrent weekly gemcitabine at our institution from February 2013 to December 2018. Overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and the pattern of recurrence and toxicity were analysed.ResultsFifteen patients received treatment during the study period. The median age was 78 years (range 75–86 years), and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) of all patients was 0–1. The median survival time (MST) and median PFS were 20.4 [95% confidence interval (CI) 10.3–36.8] and 13.5 (95% CI 6.4–20.3) months, respectively, and the 1-year OS and PFS rates were 80.0% (95% CI 50–93.1%) and 66.7% (95% CI 37.5–84.6%), respectively. The median LRPFS and median DMFS were 15.6 (95% CI 6.4–36.8) and 14.9 (95% CI 7.0–20.5) months, respectively, and the 1-year LRPFS and DMFS rates were 73.3% (95% CI 43.6–89.1%) and 66.7% (95% CI 37.5–84.6%), respectively. Non-haematologic grade 3 toxicity was observed in three cases, of which only one was induced by radiotherapy, whereas grade 4–5 non-haematologic acute or late toxicities were not observed.ConclusionsThe OS and PFS of elderly patients with LAPC treated using hypofractionated IMRT with concurrent gemcitabine were favourable and without the occurrence of severe toxicity. This treatment strategy is feasible and promising for elderly LAPC patients with good PS.

Nomogram Predicting the Benefits of Adding Concurrent Chemotherapy to Intensity-Modulated Radiotherapy After Induction Chemotherapy in Stages II-IVb Nasopharyngeal Carcinoma.

BackgroundTo compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus induction chemotherapy plus radiotherapy (IC+RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Patients and MethodsOne thousand three hundred twenty four patients with newly-diagnosed NPC treated with IC+CCRT or IC+RT were enrolled. Progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), locoregional relapse-free survival (LRFS), and acute toxicities during radiotherapy were compared using propensity score matching (PSM). A nomogram was developed to predict the 3- and 5-year PFS with or without concurrent chemotherapy (CC).ResultsPSM assigned 387 patients to the IC+CCRT group and IC+RT group, respectively. After 3 years, no significant difference in PFS (84.7 vs. 87.5%, P = 0.080), OS (95.5 vs. 97.6%, P = 0.123), DMFS (89.7 vs. 92.8%, P = 0.134), or LRFS (94.0 vs. 94.1%, P = 0.557) was noted between the groups. Subgroup analysis indicated comparable survival outcomes in low-risk NPC patients (II–III with EBV DNA <4,000 copies/ml) between the groups, although IC+RT alone was associated with fewer acute toxicities. However, IC+CCRT was associated with significantly higher 3−year PFS, OS, DMFS, and LRFS rates, relative to IC+RT alone, in high-risk NPC patients (IVa-b or EBV DNA ≥4,000 copies/ml). Multivariate analysis showed that T category, N category, EBV DNA level, and treatment group were predictive of PFS, and were hence incorporated into the nomogram. The nomogram predicted that the magnitude of benefit from CC could vary significantly.ConclusionsIC+RT had similar efficacy as IC+CCRT in low-risk NPC patients, but was associated with fewer acute toxicities. However, in high-risk patients, IC+CCRT was superior to IC+RT.

Prognostic value of post-radiation serum squamous cell carcinoma antigen and primary tumor regression for cervical squamous cell carcinoma.

In this study, we determined the prognostic values of magnetic resonance imaging (MRI)-based primary tumor regression and serum squamous cell carcinoma antigen (SSCC-Ag) levels 4 weeks after definitive radiotherapy (RT) in cervical squamous cell carcinoma (CSCC) patients. This was a retrospective study involving 218 patients with histologically confirmed CSCC (stages IB-IVA). All the patients received definitive RT. Pre- and post-RT pelvic MRI and SSCC-Ag levels were measured. Locoregional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated, and possible OS prognostic factors were analyzed. The median follow-up time was 25.57 (1.73-58.93) months. Thirty-six and 68 patients died and experienced recurrence, respectively, and the primary tumors of 130 (59.6%) and 88 (40.4%) patients exhibited complete response (CR) and non-CR, respectively. The 3-year OS, DFS, LRC, and DMFS rates were significantly higher in the CR than in the non-CR patients (85.2% vs. 67.9%, 78.9% vs. 39.0%, 93.4% vs. 63.8%, and 83.4% vs. 54.5%, respectively; p< 0.05). The 3-year OS, DFS, LRC, and DMFS rates were significantly lower in the patients with high post-RT SSCC-Ag levels than in those with low post-RT SSCC-Ag levels (38.0% vs. 83.9%, 21.2% vs. 66.3%, 73.0% vs. 84.9%, and 26.5% vs. 79.0%, respectively; p<0.05). Multivariate analyses indicated that SSCC-Ag levels were an independent OS predictor (HR: 5.749, 95% CI: 2.598-12.723, p< 0.001). Post-RT SSCC-Ag levels are OS independent prognostic factors in CSCC patients receiving RT. Timely and optimized treatment plans for CSCC patients after 4 weeks of RT are necessary when patients with persistent tumor and/or positive SSCC-Ag.

Single Center Results With SRS And FSRT In Uveal Melanoma

To assess the results of stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) in patients with uveal melanoma. Data of 417 patients treated with SRS/FSRT between September 2007 and November 2019 in our center were retrospectively evaluated. All treatments were applied via CyberKnife®. Median age of patients was 56 years. 201 (48%) patients were female and 216 (52%) were male. One patient had bilateral tumors, so the number of treated tumors was 418. 77% of tumors were T2-3, and 13% had ciliary body invasion. Total SRS/FSRT dose was <45 Gy in 100 (25%), and ≥45 Gy in 313 (75%) patients, respectively. Median tumor basal diameter was 8 mm (1.5-23 mm) and depth 8 mm (1-21 mm). Median tumor volume was 594 mm3 (23-9.158 mm3). Visual acuity was measured in 298 patients at the time of diagnosis. Other tumor and treatment characteristics are given in Table 1. Median follow-up was 48 months (0-263 months). The rate of 2-, 5-, and 10-year overall survival (OS) was 95%, 83%, and 68%, and distant metastasis-free survival (DMFS) was 91%, 77%, and 63%, respectively. Enucleation was performed in 92 patients; due to tumor progression in 59, and RT complication in 21 patients, respectively. The 2-, 5-, and 10-year enucleation-free survival (EFS) in all patients was 80%, 61%, and 50%, respectively. In univariate analysis, the rates of OS and DMFS were similar with ≥45 Gy and <45 Gy but 2- and 5-year EFS rates were significantly higher with ≥45 Gy (82% and 66% vs. 76% and 50% with <45 Gy, p = 0.006). The rates of OS, DMFS, and EFS were significantly lower in patients with a tumor diameter ≥8 mm. In patients with a tumor depth ≥8 mm, the rates of DMFS and EFS were significantly lower. In patients with a tumor volume <600 mm3, the rates of OS, DMFS, and EFS were significantly higher. Among patients that received ≥45 Gy, the ones with a tumor volume <600 cm3 had significantly higher rates of DMFS and EFS but OS was similar. In multivariate analysis, no prognostic factors were found for DMFS. However, for OS and EFS >8 mm basal tumor diameter (relative risk [RR] = 1.6, 95% confidence interval [CI] = 1.92-3.12, p = 0.09; and RR = 1.8, 95% CI = 1.15-2.81, p = 0.01), for EFS >8 mm depth (RR = 1.6, 95% CI = 1.03-2.4, p = 0.03), and ≤45 Gy dose (RR = 1.4, 95% CI = 0.9-2.08, p = 0.06) were negative prognostic factors. SRS/FSRT-related late toxicity was significantly higher in patients with a basal tumor diameter >8 mm and depth >8 mm (p = 0.001 and p = 0.04, respectively). Total SRS/FSRT dose and tumor diameter and depth were found prognostic factors for EFS. Toxicity rate was higher in patients with a higher tumor depth and basal diameter.Abstract 3685; TableCharacteristicNumber of patients (%)Tumor location • Anterior• Posterior52 (12)366 (88)T stage • T1• T2• T3• T4• Unknown88 (21)159 (37)142 (34)20 (5)9 (3)COMS • Small• Medium• Large• Unknown38 (9)257 (62)118 (28)5 (1)Visual acuity at diagnosis (in 298 patients) • Full loss• p-eh• mps- 0.1• 1- 0.4• 4- 0.6• 0.7 and higher1 (1)59 (20)62 (21)61 (20)62 (21)53 (17) Open table in a new tab

Excellent Local Control and Survivals after Particle Beam Radiation Therapy for Skull Base Malignancies

Complete resection of skull base malignancies (SBM) is challenging, and prognoses of patients with unresected or incompletely resected SBM is suboptimal. Radiotherapy (RT) plays a significant role in the treatment of SBM. Particle beam radiation therapy (PBRT), such as proton and carbon-ion radiotherapy (PRT and CIRT) demonstrates prominent advantages with its physical properties which enable improved dose coverage to the tumor target(s) and avoid overdosing to adjacent organs at risk thereby achieve optimal efficacy and safety. The purpose of this study is to report the clinical outcomes of intensity modulated PBRT for a relatively large group of patients with SBM. All patients with SBM (chordoma excluded due to its indolent behavior) treated at the Shanghai Proton and Heavy Ion Center from 06/2014 to 07/2019 were included in this analysis. The overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were calculated using the Kaplan-Meier method. Multivariate analyses (MVA) on survivals were performed using Cox proportional hazards model. Indicators used for MVA included age, sex, pathology, T-category, status of recurrence (post-RT or surgery), R0/1 vs. R2 resection, use of chemotherapy, and PBRT technology (PRT vs. CIRT vs. PRT+CIRT). Acute and late toxicities were assessed with the CTCAE (v. 4.03). Among the 176 consecutive patients with SBM (adenoid cystic carcinoma 53, soft tissue sarcoma 31, chondrosarcoma 29, squamous cell carcinoma 19, melanoma 12, adenocarcinoma 10, esthesioneuroblastoma 8, osteosarcoma 6, and other histologies 8) treated, 134 patients (76.1%) had locally advanced (T3/4) disease, 136 (77.3%) were radiation-naïve and 40 (22.7%) failed prior radiotherapy, and 134 (76.1%) received R2 resection before PBRT. Patients were treated with CIRT (n = 126) alone, PRT (n = 9) alone, or PRT+CIRT boost (n = 49). The median dose was 66 Gy (RBE). Chemotherapy was used in 20.5% of the patients. With median follow-up of 20.0 months, the 1-/2-year OS, LRFS, and DMFS, and PFS rates were 93.9/87.1%, 90.3/82.2%, 89.9/84.9%, and 66.1/46.6%, respectively. On MVA, age of ≥ 40 was associated with significantly worse OS (p = 0.05) and PFS (p = 0.02). Patients presented with failure after prior radiotherapy (p = 0.009) or surgery (p = 0.029) had significantly worse LRFS after PBRT. Additionally, higher T-classification (i.e., T3/T4) (p = 0.017) and recurrence after surgery (p = 0.06) was associated with significantly worse PFS (Table). Severe (≥ grade 3) acute toxicities included mucositis (n = 1), visual impairment (n = 2), and hemorrhage (n = 1). Severe late toxicities included oligosialia (n = 2), decreased vision (n = 2), osteonecrosis (n = 1), and hemorrhage (n = 1). PBRT provides effective disease control and survivals for SBM with favorable toxicity profiles. Further follow-up is needed to understand the long-term efficacy and safety.

Value Of Radiotherapy After Minimally Invasive Surgery In Patients With Stage IA1-IIA1 Cervical Cancer

In this study, we aimed to estimate the value of adjuvant radiotherapy after receiving laparoscopic hysterectomy for stage IA1-IIA1 cervical cancer patients. Two hundred twenty-one women with cervical cancer of stage IA1-IIA1 were included in this retrospective analysis. Sixty-two of them were treated with laparoscopic hysterectomy and adjuvant radiotherapy (group A), 115 underwent open surgery (group B) and 44 performed laparoscopic hysterectomy alone (group C). The 3-year local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were assessed in three groups. The median follow-up time was 58.33 months (range, 56.91–59.76 months) for all the patients. Three groups were comparable in terms of age, histologic subtypes, tumor size and ECOG Performance Status. The 3-year LRFS rates were 98.4% in group A, 97.4% in group B, 86.4% in group C, respectively. The LRFS rate of group A and B patients surpassed those of group C patients (group A vs. B, p = 0.634; group A vs. C, p = 0.011; group B vs. C, p = 0.006). The 3-year overall survival (OS) and 3-year DMFS rates were 96.8% and 93.5% in group A, 97.4% and 98.3% in group B, 93.2% and 97.7% in group C, respectively. The 3-year OS and DMFS rates were comparable in three groups (p>0.05). Adjuvant radiotherapy after laparoscopic hysterectomy in patients with early stage cervical cancer can reduce the risk of recurrence, and bring local control and survival benefits.

70-Gene Signature as an Aid to Treatment Decisions in Early Breast Cancer: Updated Results MINDACT

Background: The MINDACT trial showed excellent 5-year distant metastasis-free survival (DMFS) of 94·7% (95%CI 92·5-96·2) in clinical high (C-High)/genomic low (G-Low) risk patients who did not receive chemotherapy. Long-term follow-up is presented. Methods: 6693 patients were enrolled 2007 to 2011. We reassessed DMFS rate at 5 years in C-High/G-Low patients not receiving chemotherapy (n=644) (primary analysis), updated DMFS and overall survival in C-High/G-Low patients receiving chemotherapy or not (n=749 and 748, respectively) (secondary analysis), and examined a potential age effect ( 50y) for women with HR+/HER2- disease. Findings: At a median follow-up of 8·7 years, the updated 5-year DMFS rate for C-High/G-Low patients receiving no chemotherapy is 95·1% (95%CI 93·1-96·6), above the predefined non-inferiority boundary of 92%, proving MINDACT as a positive de-escalation trial.The 5-year and 8-year outcome of C-High/G-Low patients show a respective 0·9% (SE ±1·1) 2·6% (SE ±1·6) difference in DMFS for chemotherapy versus no chemotherapy (HR 0·66; 95%CI 0·48-0·92), without differences in overall survival (95·7% vs 94·3%).The same comparisons confined to HR+/HER2- disease (91% of patients) generate different gain estimates from chemotherapy administration for DMFS according to age: 5% (SE ±2·8%) in women ≤50 years versus 0·2% (SE ±2·3%) in women > 50 years. Interpretation: The clinical utility of a low risk 70-gene signature for foregoing adjuvant chemotherapy in the presence of a high clinical risk (and up to 3 positive nodes) remains proven. In C-high/G-low patients > 50 years chemotherapy did not improve outcome across the whole follow-up trajectory. At longer follow-up in younger women, while underpowered, a clinically relevant benefit of about 5% was observed, possibly due to chemotherapy-induced ovarian function suppression, and should be part of informed, shared decision-making. Trial Registration: ClinicalTrials.gov number, NTC00433589; EudraCT number, 2005-002625-31. Funding Statement: Funded by the European Commission Sixth Framework Programme and other grants. Declaration of Interests: None to declare. Ethics Approval Statement: All patients gave written informed consent. The ethics committees of all participating sites approved the study, which involved collaboration of seven member groups under the Breast International Group umbrella.

Extranodal Expansion Of The Lymph Nodes Is An Effective Predictor Of Distant Metastasis Of Nasopharyngeal Carcinoma After Radical Radiotherapy And Chemotherapy

Extranodal extension (ENE) of the lymph nodes is a criterion for advanced nodal staging of oropharyngeal and hypopharyngeal carcinoma. The purpose is to investigate whether ENE is a factor affecting distant metastasis of nasopharyngeal carcinoma after radical radiotherapy and chemotherapy. From January 2009 to December 2014, 318 patients of NPC after radical radiotherapy and chemotherapy were enrolled. All patients received radical intensity-modulated radiotherapy. Concurrent chemotherapy was cisplatin intravenous drip every 3 weeks for 4-6cycles.MRI was retrospectively reviewed in all patients and the ENE of the lymph nodes was evaluated in patients with metastatic lymph nodes. According to the tendency of disease metastasis, patients were divided into ascending and descending types. Ascending type (Type A,T3-4N0-1) was defined as advanced local disease and early-stage cervical lymph-node involvement; advanced lymph-node metastases but early -stage local disease was classified as descending type (Type D,T1-2N2-3). Kaplan-Meier methods and Cox proportional hazard models were used to evaluate the impact of different types on distant metastasis free survival. The 5-year distant metastasis-free survival (DMFS) rate of all patients was 85%. There were 143 patients with type A and 175 patients with type D. Compared with type A, type D had worse 5-year DMFS (95% vs 78%; P < 0.05). For type A, univariate analysis and multivariate analysis suggested that ENE was closely related to distant metastasis (P < 0.05). Compared with negative ENE, ENE positive had a higher probability of metastasis within 5 years (DMFS: 99% vs 66.7%; P < 0.05). The independent prognostic factors of type D distant metastasis are ENE and the number of positive lymph nodes. ENEpositive is more likely to have distant metastasis than ENEnegative (DMFS: 84% vs 62.7%). Compared with patients with more than 4 positive lymph nodes, patients with less than 4 positive lymph nodes have significantly better DMFS (83.7% vs 90.9%; P < 0.05 for all). Patients with type D was more likely to metastasize than type A, but no matter how it was typed, ENE was an independent factor affecting distant metastasis and could be considered as a new standard for NPC lymph node staging.

The Contribution of Intensity-Modulated Radiotherapy after Non-curative Intent Surgery for Head and Neck Adenoid Cystic Carcinoma

Incomplete surgery (gross total resection, near total resection, and subtotal resection) of head and neck adenoid cystic carcinoma (HNACC) is controversially considered as an unfavorable prognostic factor as to curative intent surgery (CIS). However, in Intensity-Modulated Radiotherapy (RT) era, after planed incomplete surgery (PIS), intensified RT or RT with concurrent chemotherapy (CCT) may contribute to tumor control and survival. Thus, we investigated the contribution of IMRT after PIS on local control and survival in HNACC. Retrospective review was performed for 170 consecutive patients with HNACC treated with curative postoperative IMRT with or without concurrent chemotherapy, between 2015 and 2018, after PIS (n = 102) or CIS (n = 68). All plan target volumes were designed to including the primary tumor and related cranial nerve pathway. Patients with other malignant tumors or distant metastasis were excluded. Among the 170 patients (98 women and 72 men; median age, 53 years), the median follow-up time was 27.8 (range, 9.6-59.1) months. The estimated 3-year local-regional recurrence-free survival (LRRFS) rate, progression-free survival (PFS) rate, overall survival (OS) rate, and distant metastasis-free survival (DMFS) rate were 92.4% (95%CI: 87.3-95.9), 74.7% (95%CI: 67.5-81.0), 98.5% (95%CI: 94.9-99.6), and 76.0% (95%CI: 68.7-82.1), respectively. Patients with high grade, Ki-67≥10%, Stage III-IV, extra-nodal extension (ENE), perineural invasion (PNI) and positive margin was associated with worse PFS (p<0.0001, p = 0.002, p = 0.003, and p = 0.0004, p = 0.042, and p = 0.021, respectively). The baseline and treatment characteristics were equally distributed between PIS and CIS group, except that there were more patients with positive margin and received RT dose≥66 Gy in PIS group (p = 0.000 and p = 0.000). There was no difference in LRRFS, DFS, OS, and DMFS between two groups, both in stage I-II and Stage III-IV (p = 0.280, p = 0.371, p = 0.752, and p = 0.549, respectively). Among patients with high grade, Ki-67≥10%, ENE or PNI, there was also no difference in PFS between two groups. Among patients received radiation dose<66Gy, PIS group patients had significant worse PFS (p = 0.029), while among patients without any CCT, PIS group patients had marginal significant worse PFS (p = 0.067). In IMRT era, PIS does not compromise oncologic treatment, even in patients with worse prognostic factors; however, Doses of ≥66 Gy or CCT might be essential. This strategy warrants further evaluation in prospective randomized trials with longer follow-up.

Longitudinal Trend of Health-Related Quality of Life During Concurrent Chemoradiotherapy and Survival in Patients With Stage II-IVb Nasopharyngeal Carcinoma.

Background and Aims: To investigate the longitudinal trend of health-related quality of life (HRQOL) from the start to the end of concurrent chemoradiotherapy and survival in patients with advanced nasopharyngeal carcinoma (NPC).Methods: A total of 145 patients with stage II–IVb NPC, who were a subsample of a randomized phase III clinical trial, were recruited in this study. HRQOL was measured weekly for a total of 6 weeks during concurrent chemoradiotherapy by the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30. Longitudinal trends of HRQOL domains over time were analyzed using mixed models. Survival rates were estimated using Kaplan-Meier method.Results: During a median follow-up of 45 months, the 3-year progression-free survival rate, overall survival rate, and distant metastasis-free survival rate were highly at 86.8% (95% CI: 80.1%, 91.4%), 95.1% (95% CI: 90.1%, 97.6%), and 91.0% (95% CI: 84.9%, 94.6%), respectively. The average weekly declines of five functioning domains were 1.83–3.52 points during the treatment period, with role functioning having the largest decline rate (−2.52 points per week, 95% CI: −4.50, −2.55; p < 0.001). Loss of appetite is the most affected symptom, with severe appetite loss ranging from 35.9 to 61.1%. The average increases of symptoms were 0.63–5.16 points per week during treatment period (all p-values for time <0.001, except for financial difficulties), with pain symptoms having the largest increase (5.16 points, 95%CI: 4.25, 6.08; p < 0.001), followed by fatigue (3.62 points, 95%CI: 2.90, 4.35; p < 0.001).Conclusion: The HRQOL of patients with advanced NPC is poor and substantially deteriorated during the concurrent chemoradiotherapy (CCRT) period. Psychological care and support is necessary for patients with advanced NPC during the treatment period.

Targeted Intraoperative Radiotherapy Is Non-inferior to Conventional External Beam Radiotherapy in Chinese Patients With Breast Cancer: A Propensity Score Matching Study.

Purpose: To investigate the efficacy of targeted intraoperative radiotherapy (TARGIT) vs. conventional external beam radiotherapy (EBRT) in Chinese patients with breast cancer.Methods: We retrospectively analyzed breast cancer patients who underwent breast-conserving surgery (BCS) at our hospital between April 2009 and October 2017. Patients were divided into TARGIT group and EBRT group according to different radiotherapy methods. TARGIT was performed with low-energy X-rays emitted by the Intrabeam system to deliver a single dose of 20 Gy to the applicator surface. Propensity score matching was performed at 1:1. The Kaplan–Meier method was used to calculate the locoregional recurrence (LR), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) of the two groups, and the log-rank test was run to analyse between-group difference before and after matching.Results: A total of 281 patients were included, with a median follow-up of 43 months. Of them, 82 were included in the TARGIT group and 199 in the EBRT group. Using the risk-adapted approach, 6.1% of patients received supplemental EBRT in the TARGIT group. The 5-year LR rate was 3.2% in the TARGIT group and 3.1% in the EBRT group (P = 0.694), the 5-year DMFS rates were 100 and 96.7%, respectively (P = 0.157); the 5-year DFS rates were 96.8 and 94.2% (P = 0.604); and the 5-year OS rates were 97.6 and 97.8% (P = 0.862). After matching which eliminated interference from imbalanced baseline factors, 128 matched patients were analyzed by the Kaplan–Meier method. The 5-year LR rate was 2.3% in the TARGIT group and 1.6% in the EBRT group; the 5-year DMFS rates were 100 and 98.4%, respectively; the 5-year DFS rates were 97.7 and 98.4%; and the 5-year OS rates were 98.4 and 98.4% (P = 0.659, 0.313, 0.659, 0.987). There was no significant difference in efficacy between TARGIT group and EBRT group.Conclusion: TARGIT and EBRT have similar 5-year outcomes in selected Chinese breast cancer patients undergoing BCS, and it can be used as an effective alternative to standard therapy, with substantial benefits to patients. The results need to be further confirmed by extending the follow-up time.