Locoregional Relapse-free Survival Research Articles

De-Escalated Radiotherapy for Advanced Stage Wilms Tumor: A Single-Center Experience

<h3>Purpose/Objective(s)</h3> Survival rates have dramatically improved in Wilms tumor (WT) with multimodal treatment. Herein, we aimed to compare the efficacy of 9 Gy to 10.8 Gy flank RT or whole abdominal irradiation (WAI) in patients with WT treated in a single tertiary treatment center. <h3>Materials/Methods</h3> This study includes 42 patients with a unilateral or bilateral WT with a local stage III disease who received a low-dose (10.8 Gy) or lower-dose (9 Gy) flank RT or WAI between 1998 and 2018. Patients had undergone either upfront surgery followed by adjuvant chemotherapy (CXT) or neoadjuvant CXT followed by surgery. Patients with lung metastasis without a complete response to CXT also received whole lung irradiation (WLI) of 9-12 Gy. <h3>Results</h3> The disease was staged as III in 22, IV in 12, and V in 9 patients, respectively. After a median follow-up of 75 months, the 2- and 5-year overall survival, locoregional relapse-free survival, and distant metastasis-free survival rate was 92% and 79%, 87% and 76%, and 75% and 69%, respectively. None of these survival rates were different among 9 Gy and 10.8 Gy doses. Among patients receiving WLI, the lung relapse rate was also similar between < 12 Gy and 12 Gy of irradiation. Late toxicity was observed in four (10%) patients as scoliosis, cardiac dysfunction, renal injury and hypertension, and short stature. <h3>Conclusion</h3> De-escalated RT of 9 Gy to the flank or abdomen does not compromise oncologic outcomes in patients with a local stage III WT.

3D Image-Guided Brachytherapy as Only Treatment for Stage-I Inoperable Endometrial Cancer: Retrospective Analysis of the Gynecological Cancer GEC-ESTRO Working Group

Analyze the outcomes of stage-I inoperable endometrial cancer (EC) patients treated with 3D-image-guided brachytherapy without external beam irradiation hypothesizing that this treatment provides very good results.Medical records of EC patients treated in 7 European centers from 2004-2018 with exclusive IGBT were examined, including: an aesthetic procedure, applicator type, BT-planning imaging, clinical target volume (CTV), BT schedule, overall daily dose equivalent to 2Gy fractions (EQD2(α/β = 4,5 or 3)) to the CTV(α/β = 4,5) and D2cm3(α/β = 3) for organs at risk. Complications were evaluated using CTCAEv4 scores. Survival probability at 2 and 5 years was estimated (cancer-specific survival [CSS], disease-free survival [DFS], local relapse-free survival [LRFS], loco-regional relapse-free survival [LRRFS] and distant metastasis-free survival [DMFS]).Survival analysis included descriptive analysis and the Kaplan-Meier method.A total of 62 patients staged IA (41) and IB (21) were included. Mean follow-up: 32.8 months (SD 33.7). Spinal anesthesia (38/62) followed by no anesthesia (16/62) were most common. Y-Shaped Rotte was the most common (in 74% of patients) and high-dose radiation (HDR) was used in 89%. Median D90 EQD2(α/β = 4.5) to the CTV was 58.9Gy (8.66-144Gy). Eight patients presented relapse: uterine in 4, nodal in 4 and distant in 4. At 2- and 5-years CSS was 93.3% and 80.5%, DFS 84.8% and 80.5%, LRFS was 93.1% and 88.7%, LRRFS was 91% and 91% and DMFS was 90.2% and 90.2% respectively; CSS in stages-IA and IB at 2 and 5 years was 96.6% and 88.7% vs. 77.5% and 64.6% respectively (P = 0.043). Late vaginal and bladder G3-complications rates were 2.1%, respectively.Inoperable EC patients can be safely treated by BT with CSS at 2 and 5 years of 93% and 80.5%, respectively, and better results for stage IA cases. Prospective studies on 3D-image-guided BT can help better analyses patient outcomes and draw dose/volume effect relationships for tumor control.

Nomogram-aided individual induction chemotherapy regimen selection in advanced nasopharyngeal carcinoma

ObjectiveWe undertook this study to clarify how TPF, TP and PF induction chemotherapy (IC) regimens benefit for nasopharyngeal carcinoma (NPC) patients with different risk of disease progression. Materials and MethodsPatients with newly diagnosed, stage III-IVA NPC were included. A quantitative nomogram was built using the independent prognostic factors identified for disease-free survival (DFS). Patients were stratified into low-risk and high-risk groups by the nomogram. Survival outcomes and toxicities between different IC regimens were compared. ResultsIn total, 1647 (41.0%), 1123 (28.0%) and 1242 (31.0%) patients received TPF, PF and TP regimen, respectively. Consequently, 2253 (56.2%) patients were clarified as low-risk group and the other 1759 (43.8%) as high-risk group. Survival outcomes did not significantly differ between TPF, PF and TP regimens within the low-risk group. However, TPF was associated with significantly improved 3-year DFS (76.2% vs. 67.5% vs. 68.3%), overall survival (88.3% vs. 84.1% vs. 83.9%), distant metastasis-free survival (81.9% vs. 75.0% vs. 77.4%) and locoregional relapse-free survival (92.0% vs. 87.5% vs. 86.9%; all P < 0.05) compared with PF and TP within high-risk group. Multivariate analysis also confirmed these findings. Toxicity analysis showed that TP regimen has the highest percentage of grade 3–5 hematologic toxicities while PF regimen achieved the lowest percentages of overall grade 3–5 adverse events. ConclusionsPatients with high risk should receive TPF for better efficacy and PF may be a better choice for low-risk patients with regard to less grade 3–5 toxicities.

Retrospective Analysis of Induction Chemotherapy plus Concurrent Chemoradiotherapy under Intensity-Modulated Radiotherapy Mode for Locally Advanced Nasopharyngeal Carcinoma

Introduction: Nasopharyngeal carcinoma (NPC) originates from the mucous epithelium of the nasopharynx. Although induction chemotherapy plus concurrent chemoradiotherapy is the major therapeutic protocol used for locally advanced NPC without metastasis, more research studies are needed to evaluate the curative effects. We aim to identify the therapeutic effects and prognosis after induction chemotherapy plus concurrent chemoradiotherapy in the treatment of locally advanced NPC under the intensity-modulated radiotherapy mode. Methods: The patients (N = 544) with locally advanced NPC (III and Iva, UICC 8th) after intensity-modulated radiotherapy with induction chemotherapy and concurrent chemoradiotherapy were included in this study. We analyzed the characteristics of patients including gender, age, smoking status, tumor node staging system, clinical stage, pathological type, the therapy protocol of induction chemotherapy and concurrent chemoradiotherapy, and chemotherapy prescription. Results: We have found the 5-year survival rates of overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 85.21%, 78.51%, 90.71%, and 85.21% in follow-up, and these data indicated that our therapeutic procedure provided beneficial effects on survival rates. Subsequently, the chemotherapy drug based on docetaxel (DOC) provided a more beneficial effect on survival rate compared with taxol (TXT) (all estimated HR >1; p = 0.005, 0.004, and <0.001 of OS, PFS, and DMFS), but there was no significant difference between chemotherapy drugs based on cisplatin (DDP) and nedaplatin (NDP) in treating NPC patients (p = 0.390, 0.549, 0.364, and 0.645 of OS, PFS, LRRFS, and DMFS). The therapeutic effects of induction chemotherapy revealed no difference between TPF and TP (T: DOC or TXT, P: DDP or NDP, and F: 5-fluorouracil) (p = 0.541, 0.897, 0.498, and 0.765 of OS, PFS, LRRFS, and DMFS). In addition, there was also no significant change between concurrent chemotherapy with TP dual drugs or a single platinum drug (being excluded in the multivariate model using forward [Wald] procedure). Moreover, the survival rate showed no difference between platinum accumulation dose of more or less than 150 mg/m² for concurrent chemotherapy (being excluded in the multivariate model using forward [Wald] procedure). Conclusion: Our results indicate that induction chemotherapy plus concurrent chemoradiotherapy under intensity-modulated radiotherapy which is the standard therapeutic method for locally advanced NPC provides beneficial therapeutic effects, and it is worthy of further study.

Prognostic Significance of Circulating Lymphocyte Subsets Before Treatment in Patients with Nasopharyngeal Carcinoma.

PurposeWe set out to explore the prognostic value of circulating lymphocyte subsets in patients with nasopharyngeal carcinoma (NPC) before treatment and to investigate changes in lymphocyte subsets resulting from chemoradiotherapy.Patients and MethodsThis retrospective study included 677 patients with non-metastatic NPC. The cutoff value of lymphocyte subsets was determined by the receiver operating characteristic curve (ROC), and the prognostic significance of lymphocyte subsets was evaluated by the Log rank test and Cox proportional hazards model. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). Differences in lymphocyte subsets before and after chemoradiotherapy were analyzed by Wilcoxon signed rank test.ResultsNPC patients with high levels of CD19+ B cells (>9.55%) had better 5-year OS (90.4% VS 76.8%, P < 0.001), 5-year PFS (85.3% VS 71.6%, P < 0.001) and 5-year DMFS (94% VS 86.8%, P = 0.002) than patients with low levels of CD19+ B cells. Patients with high levels of CD4+ T cells (> 37.05%) had better 5-year PFS (83% VS 74.2%, P = 0.015) and better 5-year DMFS (95.8% VS 86.7%, P < 0.001) than those with low levels of CD4+ T cells. Multivariate analyses indicated that CD19+ B cell was an independent prognostic factor for OS, PFS and DMFS in NPC. And CD4+ T cell was an independent prognostic factor for PFS and DMFS. Within 1 month after chemoradiotherapy, the percentages of CD4+ T cells, CD19+ B cells, and the CD4/CD8 ratio decreased significantly, while the percentages of CD8+ T cells increased significantly.ConclusionNPC patients with low levels of CD19+ B cells or CD4+ T cells before treatment have a poor prognosis. In addition, chemoradiotherapy may reduce the body’s immune function in NPC patients.

Clinicopathological, immunohistochemical and treatment features of metachronous versus synchronous bilateral breast carcinoma

Objectives. The purpose of this study was to assess and compare the clinicopathological, molecular pathology, treatment and survival characteristics in patients with metachronous bilateral breast cancer (mBBC) and synchronous breast cancer (sBBC). Materials and methods. A cohort of 658 patients with breast cancer treated at the Coltea Clinical Hospital, Surgery Department, between January 2015 and December 2019 and followed-up until August 2020 was studied. Data pertaining to patients who were diagnosed as having bilateral breast cancer were retrospectively reviewed and collected. A 3-months interval was used to distinguish metachronous from synchronous tumors. Among patients with bilateral breast cancer, assessment parameters included patient characteristics, histological and molecular pathology features and the performed treatment that were statistically evaluated comparing the first and second tumor of each group and among groups. Survival analysis was performed comparing mBBC and sBBC patients. SPSS was used for data analysis. Outcomes. Of the 658 patients with primary breast cancer, 35 (5.3%) patients were diagnosed as having bilateral breast cancer (25 (3.8%) mBBC and 10 (1.5%) sBBC). When clinical and histopathological parameters were statistically evaluated, age, menopausal status, tumor size, number of invaded nodes and anatomic stage were found to be significant between the tumors of the metachronous group and tumor size, pathologic T(tumor) and stage between tumors of the synchronous group. Hormonal receptor (HR) status concordance was higher in the synchronous group (85.7%, p = 0.010), with a higher percentage of ER positive (71.4%) and PR positive (71.4%) concordance of the tumors. In terms of survival analysis, there was a difference in overall survival (OS, p = 0.005), disease-free survival (DFS, p = 0.011) and distant relapse-free survival (p = 0.003) between mBBC and sBBC. The mean disease-free survival for patients in whom metachronous tumor occurred within less than 5 years was 63.3 months, for sBBC patients was 39.6 months, whereas for patients with more than 5 years was 437.9 months (p = 0.012, Log Rank). Discordant biomarker defined subgroup (ER,HER2) patients were associated with better disease-free survival (p = 0.047, Log Rank) and better distant relapse-free survival (p = 0.015, Log Rank) in overall patients. In terms of loco-regional relapse-free survival, although mBBC and sBBC patients showed no statistical significant difference earlier in the time course (p = 0.088, Breslow; p = 0.054 Tarone-Ware), among mBBC patients was observed a better outcome (p = 0.027, Log Rank). Conclusions. Based on survival analysis, patients in whom metachronous tumor developed after more than 5 years, had a better distant relapse-free survival. Patients with synchronous bilateral breast cancer were associated with worse disease outcome based on overall survival analysis and disease free-survival rates with more frequent rates of distant metastasis. Outcome of patients in whom metachronous tumor was diagnosed within less than 5 years might be similar to synchronous tumors. Patients with discordant ER,HER2 status showed a better disease outcome. Although concordance in HR status and molecular subtype, did not show statistical significant differences, it is a subject which deserves further clinical observation.

The Effect of Prolonged Duration of Intensity Modulated Radiotherapy for Nasopharyngeal Carcinoma.

PurposeRadiotherapy is the most important primary treatment for patients with nasopharyngeal carcinoma. Generally, the treatment duration of radiotherapy takes six or six and half weeks with 30 to 33 fractions. The current study was conducted to evaluate the association between prognosis and the duration of radiotherapy in nasopharyngeal carcinoma patients.MethodsPatients with primary nasopharyngeal carcinoma who were treated with intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy, with or without induction chemotherapy between January, 2008 and December, 2013 at a single institution were retrospectively reviewed.ResultsIn total, 1292 patients were included. At a median follow-up of 71.0 months (range 2.0–126.0 months), locoregional recurrence, distant failure and death were observed in 8.8%, 12.2% and 15.6% of all patients, respectively. Estimated 5-year locoregional relapse–free survival, distant metastasis–free survival, progression-free survival and overall survival in patients with radiation ≤ 7 weeks versus patients with radiation >7 weeks were: 93.2% versus 87.0% (P < 0.001), 89.4% versus 84.4% (P = 0.016), 79.8% versus 70.6% (P < 0.001) and 87.2% versus 78.4% (P < 0.001), respectively.ConclusionsProlonged duration of radiotherapy with a significantly higher risk of distant metastasis and death in nasopharyngeal carcinoma patients. Understanding this point, healthcare providers should make efforts to avoid prolonged duration of radiotherapy to minimize the risk of treatment failure.

Management of suboptimal response to induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Re-induction therapy or direct to Radiotherapy?

BackgroundUnsatisfactory tumor response to induction chemotherapy (IC) is an adverse prognostic factor of locoregionally advanced nasopharyngeal carcinoma (LANPC). A re-induction strategy which applies additional cycles of an alternative IC regimen prior to radiotherapy (RT) has been adopted. MethodsA total of 419 LANPC patients who attained suboptimal response (stable disease or disease progression) according to the Response Evaluation in Solid Tumors (RECIST) guideline after initial IC were retrospectively included. They were divided into those who received additional cycles of re-induction regimen prior to RT (re-induction group, n = 87) and those who had no additional chemotherapy (direct to RT group, n = 332). Propensity score matching (PSM) was used to adjust for potential confounders. Tumor response and long-term survival were compared between two groups. ResultsAfter receiving a second IC regimen, 39.1% of the patients in re-induction group attained partial response; however, the tumor control of subsequent RT was not significantly improved when compared with direct to RT group (patients attaining complete response after RT 55.2% vs. 52.5%, P = 0.757). Patients who received re-induction therapy showed worse locoregional relapse-free survival (LRFS) and progression-free survival (PFS) than those proceeded directly to RT (3-year LRFS 75.7% vs. 83.1%, P = 0.005; 3-year PFS 62.4% vs. 68.3%, P = 0.037). The increased hematological toxicities were observed in re-induction group that included grade 3–4 anemia, thrombocytopenia and liver enzyme increase. ConclusionRe-induction therapy decreased LRFS and PFS and increased toxicities among patients who attain suboptimal response to initial IC regimen, as compared with direct to RT strategy.

Prognostic value of hypertension in patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy.

BackgroundThe prognostic value of hypertension remains unknown in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). In this study, we aimed to develop hypertension as a prognostic signature for improving the clinical outcome of non-metastatic NPC patients treated with IMRT.MethodsA clinical cohort, comprising 1,057 patients with non-metastatic, histologically proven, NPC who were treated with IMRT were retrospectively reviewed. Associations between hypertension and overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) were estimated by Cox regression. A subgroup analysis of the relationship between hypertension grade and NPC prognosis was also conducted.ResultsAmong the 1057 patients, 94 (8.9%) had hypertension. Significant differences were observed between patients with hypertension and patients without hypertension in relation to OS (66.6% vs. 85.4%; P<0.0001), PFS (60.8% vs. 76.3%; P=0.001), LRRFS (85.3% vs. 90.5%; P=0.024), and DMFS (77.4% vs. 85.1%; P=0.048), and patients without hypertension had greater treatment success rates. The Cox analysis showed that hypertension was an independent unfavorable prognostic factor for OS [hazards ratio (HR), 2.056; P=0.001], PFS (HR, 1.716; P=0.005), and DMFS (HR, 1.658; P=0.049). The patients with more severe levels of hypertension had worse OS and LRRFS. Specifically, the 5-year OS and LRRFS for grades 1, 2, and 3 were 70.6%, 64.3%, and 62.4% (P=0.712), and 89.5%, 86.4%, and 76.1% (P=0.376), respectively.ConclusionsHypertension is an independent adverse prognostic factor in NPC patients treated with IMRT. The question of whether the severity of hypertension affects prognosis needs to be further verified by large sample data.

Exclusive 3D-brachytherapy as a good option for stage-I inoperable endometrial cancer: a retrospective analysis in the gynaecological cancer GEC-ESTRO Working Group.

Analyse outcomes of stage-I inoperable endometrial cancer (EC) patients from seven European centres treated with 3D-image-guided brachytherapy (IGBT) alone. From 2004 to 2018, 62 patients (41 stage-IA and 21 IB) were retrospectively studied, analysing anaesthetic procedure, applicator type, BT-planning imaging, clinical target volume (CTV), BT schedule, overall daily-dose equivalent to 2Gy (EQD2(α/β=4.5 or 3)) to the CTV(α/β=4.5) and D2cm3(α/β=3) for organs at risk. Complications were evaluated using CTCAEv4 scores. The 2 and 5year survival was calculated [cancer-specific survival (CSS), disease-free survival (DFS), local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS)]. Descriptive analysis and the Kaplan-Meier method were used for survival analysis. Mean follow-up: 32.8months (SD 33.7). Spinal anaesthesia (38/62) followed by none (16/62) were the most common. Y-shaped Rotte applicators were used in 74% of patients. High-dose rate brachytherapy was administered in 89%. Median D90 to the CTV was 58.9Gy (8.66-144Gy). Eight patients presented relapse: four uterine, four nodal and four distant. The 2 and 5year CSS was 93.3 and 80.5%, DFS 84.8 and 80.5%, LRFS was 93.1 and 88.7%, LRRFS was 91 and 91% and DMFS was 90.2 and 90.2%, respectively, CSS was better in stage-IA vs. IB (p = 0.043). Late vaginal and bladder G3-complication rates were 2.1%, respectively. Inoperable EC patients can be safely treated by BT with 2 and 5year CSS of 93 and 80.5%, respectively, with even better results for IA cases. Prospective studies on 3D-IGBT are necessary to better analyse EC patient outcomes based on dose and treated volumes.

Disseminated tumour cells from the bone marrow of early breast cancer patients: Results from an international pooled analysis

PurposePresence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC. Experimental designIndividual patient data were collected from 11 centres. Patients with EBC and available follow-up data in whom BM sampling was performed at the time of primary diagnosis before receiving any anticancer treatment were eligible. DTCs were identified by antibody staining against epithelial cytokeratins. Multivariate Cox regression was used to compare the survival of DTC-positive versus DTC-negative patients. ResultsIn total, 10,307 patients were included. Of these, 2814 (27.3%) were DTC-positive. DTC detection was associated with higher tumour grade, larger tumour size, nodal positivity, oestrogen receptor and progesterone receptor negativity, and HER2 positivity (all p < 0.001). Multivariate analyses showed that DTC detection was an independent prognostic marker for overall survival, disease-free survival and distant disease-free survival with hazard ratios (HR) and 95% confidence intervals (CI) of 1.23 (95% CI: 1.06–1.43, p = 0.006), 1.30 (95% CI: 1.12–1.52, p < 0.001) and 1.30 (95% CI: 1.08–1.56, p = 0.006), respectively. There was no association between locoregional relapse-free survival and DTC detection (HR 1.21; 95% CI 0.68–2.16; p = 0.512). ConclusionsDTCs in the BM represent an independent prognostic marker in patients with EBC. The heterogeneous metastasis-initiating potential of DTCs is consistent with the concept of cancer dormancy.

The integration of bevacizumab improves tumor response and survival in patients with refractory cervical cancer treated with radical chemoradiotherapy

BackgroundManagement of refractory cervical cancers (CC) is a debated question and rises dilemma in clinical practice. This study aimed to assess the safety and effectiveness of bevacizumab combined with concurrent chemoradiotherapy in the treatment of refractory CC.MethodsA total of 129 patients with refractory CC who received radical concurrent chemoradiotherapy (CCRT) were included in this study. Among the patients, 64 received combination treatment with bevacizumab, while the 65 remaining patients did not receive bevacizumab. Treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumorsversion1.1. The Cox proportional-hazards model was applied to determine prognostic factors associated with overall survival and the tumor response during treatment was analyzed for patients treated with bevacizumab.ResultsBevacizumab was an independent prognostic factor (P=0.017). Therefore, we only analyzed 64 patients who received combination treatment with bevacizumab. In the 64 patients treated with bevacizumab, the 3-year OS, locoregional relapse-free survival, and distant metastasis–free survival rates were 87.2%, 98.1%, and 81%, respectively. Complete clinical response rates were 37.8% (17/45) for patients with neoadjuvant chemotherapy and chemoradiotherapy after neoadjuvant chemotherapy (NACT), complete clinical response rates were 62.5% (40/64), 73.3% (33/45) and 52.6% (10/19) before brachytherapy (BT), respectively for the entire cohort, patients with NACT and chemoradiotherapy and patients with chemoradiotherapy only. The 2-year OS rate was higher for patients who achieved a complete clinical response BT than for patients who did not, 94.6% vs. 73.2%, P=0.03. Among the 64 patients who received it, 28 (43.8%) experienced hematological toxicities of grade 3 or 4, and 3 (4.7%) experienced grade 3 gastrointestinal toxicities.ConclusionsBevacizumab combined with radical chemoradiotherapy is a safe and tolerable treatment option for refractory CC, with quicker tumor regression and high OS, locoregional relapse-free survival, and distant metastasis–free survival rates.

Impact of smoking on survival in nasopharyngeal carcinoma: A cohort study with 23,325 patients diagnosed from 1990 to 2016

BackgroundWe aimed to compare the survival outcomes of patients with nasopharyngeal carcinoma (NPC) who had different smoking behaviors and were treated with two- or three-dimensional radiotherapy (2D/3DRT) or intensity-modulated radiotherapy (IMRT) with a long-term follow up. MethodsFrom 1990 to 2016, 23,325 patients with NPC were included. The primary endpoint of this study was overall survival (OS). The log-rank test and Cox proportional hazards regression model were used to assess the patients’ survival outcomes. ResultsThe 5-year OS rates in the entire cohort were 76.4%, 68.9%, and 79.8% in the former, current, and never smokers, respectively. In the IMRT cohort, the OS rates showed the same trend. Compared with the never smokers, the 5-year distant metastasis-free survival (DMFS) was lower in the former (P = 0.004) and current smokers (P < 0.001). In the multivariate analysis of the IMRT cohort, the risk of death (P = 0.003) and recurrence (P = 0.027) was higher in the current smokers, while the risk of metastasis was higher in the former and current smokers (P = 0.031 and P = 0.019, respectively) than the never smokers. A total of 53.9% of the effect of smoking status on OS was through sex, age, and Epstein-Barr virus DNA, which were significant mediators. ConclusionIn the IMRT era, being a former smoker or current smoker was an independent risk factor for DMFS. The difference in OS and locoregional relapse-free survival was significant only between the current smokers and never smokers.

Oncologic and survival outcomes in elderly patients with locally advanced rectal cancer receiving neoadjuvant chemoradiotherapy and total mesorectal excision.

The efficacy of the addition of neoadjuvant chemotherapy to neoadjuvant chemoradiotherapy and total mesorectal excision for locally advanced rectal cancer in elderly patients has not been established. A total of 3096 locally advanced rectal cancer patients who received neoadjuvant chemotherapy, along with neoadjuvant chemoradiotherapy and total mesorectal excision, with or without adjuvant chemotherapy, between January 2010 and December 2018, were studied retrospectively. Patients were divided into elderly (>75years) and younger (≤75years) groups, and propensity score matching was used to balance a potentially confounding clinical bias. Overall survival, cancer-specific survival, disease-free survival, distant metastasis-free survival and local recurrence-free survival rates for the two groups were compared. Hazard ratios (HR) with 95% confidence intervals (CI) for different clinicopathological variables were calculated to determine predictors of 3-year overall survival. Mean follow-up was 39.0 (range, 5-140) months. The overall 3-year overall survival, cancer-specific survival, disease-free survival, distant metastasis-free survival and locoregional relapse-free survival rates were 86.1, 87.6, 80.0, 82.4 and 95.4%, respectively. Only 3-year overall survival rates differed significantly between the elderly (77.2%) and younger (88.9%) groups (P=0.01). Cancer-specific survival, disease-free survival, distant metastasis-free survival and locoregional relapse-free survival rates did not differ significantly between the two groups. Significant negative independent prognostic factors for 3-year overall survival were age>75years (HR=2.016, 95% CI 1.157-23.511, P=0.01) and high pathologic TNM stage (yp stage III, P<0.001). For elderly locally advanced rectal cancer patients who have good health and performance status, the addition of neoadjuvant chemotherapy to neoadjuvant chemoradiotherapy and total mesorectal excision can result in disease-related survival rates and oncological outcomes similar to those experienced by younger patients. The decision to use this treatment approach in elderly patients should not be based solely on chronological age.

Adjuvant capecitabine in locoregionally advanced nasopharyngeal carcinoma: A multicenter randomized controlled phase III trial.

6005 Background: We conducted a multicenter, randomized controlled phase III clinical trial (NCT02143388) to investigate the efficacy and toxicity of adjuvant capecitabine (AC) in addition to concurrent cisplatin and radiotherapy (CCRT) compared to CCRT alone in high-risk locoregionally advanced nasopharyngeal carcinoma (LANPC) patients. Methods: Eligibility criteria included AJCC/UICC 7th ed TNM stage III-IVb and one of the following features: T3-4N2 or T1-4N3 or pre-treatment plasma EBV DNA concentration of &gt;20,000 copy/ml or gross primary tumor volume (GTVnx) of &gt;30 cm3 or a maximum standard uptake value (SUVmax) of &gt;10.0 by 18FDG PET-CT within the primary tumor or multiple neck node metastases, with any larger than 4 cm. All patients were randomly assigned in a 1:1 ratio to receive CCRT (3-weekly cisplatin at 100 mg/m2 for 2-3 cycles) followed by AC (1000 mg/m2 bi-daily for 14 days every 21-day cycle for 8 cycles), or CCRT alone. The prescribed radiation doses were 68-72 Gy/30-32 fractions to the PTVnx, 60-68 Gy/30-32 fractions to PTVnd, 60-64Gy/30-32 fractions to PTVhigh-risk, 54-58Gy/30-32 fractions to PTVlow-risk. Primary end point was failure-free survival (FFS). Results: Between Mar 2014 to Jul 2018, 180 patients were recruited (90 patients in CCRT+AC arm and 90 in CCRT alone arm). All patients completed RT and ≥2 cycles of concurrent cisplatin in both treatment arms (cumulative dose intensities for cisplatin were 200 mg/m2 in both arms). 85 (94.4%) patients went on to receive AC, with 71 (78.9%) patients completing 8 cycles; 19 (22.4%) patients had dose reduction of AC. With a median follow-up of 44.8 mo, the 3-y FFS was significantly superior in the CCRT+AC arm than the CCRT arm for the intention-to-treat cohort (87.7% vs 73.3%; HR: 0.52 [95% CI: 0.29-0.77], P = 0.037). 3-year overall, distant metastasis-free and locoregional relapse-free survival were 92.6% vs 88.9% (HR [95% CI]: 0.66 [0.28-1.59]), 88.8% vs. 81.1% (HR: 0.67 [0.33-1.33]) and 91.5% vs 80.0% (HR: 0.50 [0.25-1.00]), respectively. Incidences of G3-4 acute toxicities were 57.8% (52 of 90) in CCRT+AC arm and 51.1% (46 of 90) in CCRT alone arm, with a higher incidence of hand foot syndrome (3.5% vs 0%), xerostomia (11.1% vs 3.3%), mucositis (23.3% vs 16.7%), and anemia (5.6% vs 2.2%) in the CCRT+AC arm. G3-4 late toxicities occurred in 13.3% (12 of 90) and 9.0% (8 of 89), respectively. Conclusions: The addition of capecitabine to CCRT conferred a superior disease control than CCRT alone in high-risk LANPC. Survivals in ITT and PP set. Clinical trial information: NCT02143388. [Table: see text]

Anal squamous cell carcinoma: a retrospective case series.

Anal cancer is a relatively rare cancer with 660 cases diagnosed in 2000-2015 in Ireland (1). The current standard treatment is radical chemoradiotherapy (CRT). The aim of our study was to review the treatment and outcomes of patients with localised anal squamous cell carcinoma (SCC), who received radical treatment in our radiation oncology network between 2008 and 2014 inclusive. Data were collected retrospectively from ARIA® oncology information system and patient charts. Statistical analyses were performed using IBM® SPSS® statistical software version 25.0. Seventy-nine cases of anal SCC were identified. Mean age of patients at commencement of radiotherapy (RT) was 60.2years (standard deviation: 13.1years). The most common total RT dose was 50.4Gy in 28 fractions (N=58; 73.4%). Median follow-up was 5.6years. Two (2.6%) patients had persistent disease, seventeen (21.8%) patients developed loco-regional recurrence and nine (11.5%) patients developed solid organ metastases, four of whom had complete treatment response at the primary site. Eight patients underwent salvage anal surgery following completion of RT. Median overall survival was 10.5years (95% confidence interval (CI) 5.1-15.8years), median loco-regional relapse-free survival was 10.4years (95% CI 4.4-16.3years) and median disease-free survival was 9.3years (95% CI 6.3-12.2years). Our study demonstrates that treatment for anal SCC and outcomes following definitive CRT in Ireland during the study period were comparable to international standards.

Prognostic value of serum uric acid and tumor response to induction chemotherapy in locally advanced nasopharyngeal carcinoma

BackgroundTo explore the combined predictive value of serum uric acid (SUA) and tumor response to induction chemotherapy (IC) in locally advanced nasopharyngeal carcinoma (LANPC) patients receiving IC followed by concurrent chemoradiation therapy (CCRT).MethodsA total of 341 LANPC patients treated with IC + CCRT were enrolled in this retrospective study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared by the Kaplan-Meier analysis and the log-rank test, and multivariable survival analysis was carried out to investigate the independent prognostic factors.ResultsUnivariate analysis showed that a low SUA level and unsatisfactory tumor response to two cycles of IC both were negative predictors for OS, PFS, and DMFS in patients with LANPC. multivariable analysis demonstrated that the SUA level after two cycles of IC was an independent prognostic factor for OS (P = 0.012) but of borderline significance for PFS and DMFS (P = 0.055 and P = 0.067, respectively). Furthermore, tumor response to IC was of independent significance for predicting OS, PFS, and DMFS, respectively. Finally, LANPC patients with satisfactory tumor response and a high SUA level after two cycles of IC had a better OS, PFS, and DMFS than those with unsatisfactory tumor response and a low SUA level.ConclusionThe SUA level and the tumor response to two cycles of IC had predictive value for LANPC patients treated with IC plus CCRT. However, more aggressive therapeutic strategies are recommended for those with a low SUA level and unsatisfactory tumor response to two cycles of IC.

Docetaxel and cisplatin induction chemotherapy with or without fluorouracil in locoregionally advanced nasopharyngeal carcinoma: A retrospective propensity score matching analysis.

PurposeTo investigate whether the addition of fluorouracil to docetaxel and cisplatin induction chemotherapy (IC) can truly improve the prognosis of patients with locoregionally advanced nasopharyngeal carcinoma (NPC).MethodsA total of 801 patients newly diagnosed with non‐metastatic locoregionally advanced NPC were included as the subjects. In this study, propensity score matching (PSM) was used for analysis of overall survival (OS), distant metastasis‐free survival (DMFS), progression‐free survival (PFS) and locoregional relapse‐free survival (LRRFS), and the chi‐squared test or Fisher's exact test was used to investigate toxic reactions.ResultsPatients received treatment with docetaxel and cisplatin (TP) or docetaxel, cisplatin and fluorouracil (TPF). With a median follow‐up time of 60 months (range: 5–124 months), the TPF group had better 5‐year OS (84.7% vs 79.0%; P = 0.037), PFS (84.6% vs 76.8%; P = 0.008) and DMFS (89.5% vs 82.3%; P = 0.004) than the TP group. After PSM, 258 patients were matched in each cohort. The Kaplan–Meier analysis showed that the 5‐year OS, PFS and DMFS were 85.5%, 84.2% and 89.2%, respectively, in the TPF group, higher than the 80.8%, 75.0% and 81.4%, respectively, in the TP group (P = 0.048, 0.009 and 0.006, respectively). Moreover, the multivariate analysis revealed that different IC regimens were independent prognostic factors for PFS and DMFS (P = 0.014 and 0.010, respectively).ConclusionThis study found that compared with the TP regimen, TPF induction chemotherapy is associated with improved survival in patients with locoregionally advanced NPC. TPF can produce more mucosal and nausea/vomiting adverse reactions than TP.

Breast cancer larger than 2.5 cm with tumor-free radioisotope-hot sentinel nodes has higher risk of non-hot axillary lymph node metastasis

BackgroundSentinel lymph node biopsy (SLNB) is the standard axillary staging approach for early breast cancer with clinically negative axillary involvement. Adequate SLNB should include the removal of not only radioactive tracer-labeled lymph nodes (hot nodes or SLNs) but also suspicious unlabeled nodes (non-hot nodes or non-SLNs). However, the biopsy of non-hot nodes is highly dependent on the surgeons' experiences. This article aims to facilitate the surgeon's decision making by elucidating parameters that correlate with non-hot node metastasis. MethodsFrom 2013 to 2016, clinically node-negative (cN0) breast cancer patients receiving axillary SLNB using single Tc-99m tracer method at our institute were recruited. Patients were excluded if they had received prior neoadjuvant chemotherapy. Among them, cases that have at least one non-isotope-hot node biopsied were retrospectively reviewed with a particular focus on patients with pathologically negative isotope-hot SLNs. The correlation of clinicopathological data with metastasis to axillary lymph nodes and sentinel lymph nodes was analyzed with the Chi-squared test, Fisher's exact test, and multivariate logistic regression. Receiver operating curve (ROC) was applied for continuous variables that predicted non-hot node metastasis; relapse-free survival (RFS) and locoregional relapse-free survival (LRRFS) were compared by Kaplan–Meier analysis. ResultsIn 632 isotope-hot SLN negative patients, T stage showed a correlation with non-isotope-hot SLN metastasis (p = 0.035, odds ratio (OR) 9.65). Tumors larger than 2.5 cm best predict non-isotope-hot SLN metastasis (area under curve (AUC) = 0.71). With a median follow up of 41.80 months, locoregional relapse-free survival was significantly worse in cases with non-hot node metastasis (66.2% vs. 69.0%, p = 0.001). ConclusionIn the setting of SLNB using single radioisotope tracer, non-hot node metastasis in cases with negative hot SLN still carries a higher locoregional recurrence rate (13.3%). For early breast cancer larger than 2.5 cm, removal of suspicious non-hot nodes should be included for a precision therapy.

Administration of oral maintenance chemotherapy for 1 year following definitive chemoradiotherapy may improve the survival of patients with stage N3 nasopharyngeal carcinoma

ObjectivesThis study aims to evaluate the effectiveness and the optimal maintenance period of oral chemotherapy using S1 following definitive chemoradiotherapy in patients with stage N3 nasopharyngeal carcinoma (N3-NPC). Materials and methodsA retrospective review was performed for N3-NPC treatment with maintenance chemotherapy (MC) [chemoradiotherapy (CRT)-MC] or without MC (CRT-non-MC) following definitive CRT between May 2014 and December 2017. Toxicities during MC were recorded. Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were compared between CRT-MC and CRT-non-MC cohorts. The optimal duration of using maintenance S1 (MC-S1) was also analyzed. ResultsA total of 304 patients with stage N3-NPC were identified, of whom 56 were treated with CRT-MC and 248 with CRT-non-MC. After a median follow-up of 48 months, significant differences in OS (74.9 vs. 91.7%; P = 0.003), PFS (60.7 vs. 83.7%; P = 0.001) and DMFS (68.8 vs. 85.5%; P = 0.015) were observed between the CRT-non-MC and CRT-MC groups. Skin hyperpigmentation, leukopenia and fatigue were common but not severe (grade 1–2) side effects of MC. The OS, DMFS and PFS were significantly higher for patients who received S1 administration over a period of ≥12 cycles compared with those who received <12 cycles (3-year OS, 100 vs. 87.5%, P = 0.018; 3-year PFS, 93.9 vs. 67.9%, P = 0.006; 3-year DMFS, 97.1 vs. 67.9%, P = 0.002). ConclusionsUsing MC-S1 in patients with N3-NPC following definitive chemoradiotherapy achieved superior survival rate compared with the patients with non-MC. The side effects of MC-S1 were mild and tolerable. S1 should be maintained for ≥12 cycles.