Is postmastectomy radiotherapy necessary for breast cancer patients with clinically node-positive downstaging to ypN0 after neoadjuvant chemotherapy?

PURPOSE: The significance of postmastectomy radiotherapy (PMRT) in breast cancer patients who initially have clinically node-positive (cN +) status but achieve downstaging to ypN0 following neoadjuvant chemotherapy (NAC) remains uncertain. This study aims to assess the impact of PMRT in this patient subset. METHODS: Patients were enrolled from West China Hospital, Sichuan University from 2008 to 2019. Overall survival (OS), Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and breast cancer-specific survival (BCSS) were estimated using the Kaplan-Meier method and assessed with the log-rank test. The impact of PMRT was further analyzed by the Cox proportional hazards model. Propensity score matching (PSM) was performed to reduce the selection bias. RESULTS: Of the 333 eligible patients, 189 (56.8%) received PMRT, and 144 (43.2%) did not. At a median follow-up period of 71 months, the five-year LRFS, DMFS, BCSS, and OS rates were 99.1%, 93.4%, 96.4%, and 94.3% for the entire cohort, respectively. Additionally, the 5-year LRFS, DMFS, BCSS, and OS rates were 98.9%, 93.8%, 96.7%, and 94.5% with PMRT and 99.2%, 91.3%, 94.9%, and 92.0% without PMRT, respectively (all p-values not statistically significant). After multivariate analysis, PMRT was not a significant risk factor for any of the endpoints. When further stratified by stage, PMRT did not show any survival benefit for patients with stage II-III diseases. CONCLUSION: In the context of comprehensive treatments, PMRT might be exempted in ypN0 breast cancer patients. Further large-scale, randomized controlled studies are required to investigate the significance of PMRT in this patient subset.

The Effect of Postmastectomy Radiotherapy on Breast Cancer Patients After Neoadjuvant Chemotherapy by Molecular Subtype.

BACKGROUND: The effect of postmastectomy radiotherapy (PMRT) on patient outcomes after neoadjuvant chemotherapy (NAC) remains controversial. We aimed to establish a model to identify the subsets benefiting from PMRT and to examine the effect of PMRT according to molecular subtype. PATIENTS AND METHODS: We retrospectively analyzed 1118 cT1-4cN0-3M0 breast cancer patients treated with NAC and mastectomy. A nomogram predicting locoregional recurrence (LRR) was established based on 418 unirradiated patients, and X-tile analysis was performed to divide the patients into two risk groups. The effect of PMRT on LRR, distant recurrence (DR), and breast cancer mortality (BCM) was estimated for patients with different molecular subtypes in two risk groups. RESULTS: A nomogram predicting LRR was developed using six factors: histologic classification, lymphovascular invasion, ypT stage, ypN stage, estrogen receptor status, and Ki-67 expression. Our study found that PMRT correlated with lower 5-year LRR, DR, and BCM rates for the high-risk group; however, no significant improvement in these endpoints was observed in the low-risk group. Among patients with high risk, subgroup analysis showed that LRR control was improved after PMRT for the human epidermal growth factor receptor 2 (HER2)-negative/hormone receptor (HR)-positive (HER2-/HR+), HER2-positive (HER2+)/HR+, and HER2-/HR-negative (HR-) subtypes, with hazard ratios of 0.113 (95% confidence [CI] 0.034-0.379; p < 0.001), 0.159 (95% CI 0.038-0.671; p = 0.017), and 0.243 (95% CI 0.088-0.676; p = 0.007), respectively, but not for the HER2+/HR- subtype (p = 0.468). CONCLUSIONS: We built a nomogram showing favorable risk quantification and patient stratification. Patients in the high-risk group benefited from PMRT, but patients in the low-risk group did not. PMRT may show different benefits for each molecular subtype.

Comparing the 7th and 8th editions of UICC/AJCC staging system for nasopharyngeal carcinoma in the IMRT era.

BACKGROUND: To compare the prognostic value of 7th and 8th editions of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for patients with nonmetastatic nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy and simultaneous integrated boost- intensity-modulated radiation therapy (SIB-IMRT). METHODS: Patients with NPC (n = 300) who received SIB-IMRT were included. Survival by T-classification, N-classification, and stage group of each staging system was assessed. RESULTS: For T-classification, nonsignificant difference was observed between T1 and T3 and between T2 and T3 disease (P = 0.066 and 0.106, respectively) for overall survival (OS) in the 7th staging system, whereas all these differences were significant in the 8th staging system (all P < 0.05). The survival curves for disease-free survival (DFS) and locoregional recurrence-free survival (LRRFS) in both staging systems were similar, except for the comparison of T2 and T4 disease for LRRFS (P = 0.070 for 7th edition; P = 0.011 for 8th edition). For N-classification, significant differences were observed between N2 and N3 diseases after revision (P = 0.046 and P = 0.043 for OS and DFS, respectively). For staging system, no significant difference was observed between IVA and IVB of 7th edition. CONCLUSION: The 8th AJCC staging system appeared to have superior prognosis value in the SIB-IMRT era compared with the 7th edition.

Epstein-Barr virus DNA change level combined with tumor volume reduction ratio after inductive chemotherapy as a better prognostic predictor in locally advanced nasopharyngeal carcinoma.

BACKGROUND: To explore the prognosis predicting ability of the combined factors, Epstein-Barr virus DNA change level (EBVCL) and tumor volume reduction ratio (TVRR) after inductive chemotherapy (IC), in locally advanced nasopharyngeal carcinoma (LANPC). METHODS: From 2010 to 2018, 299 LANPC patients were included in this retrospective study. Receiver operating characteristic (ROC) curve analysis was performed to acquire the best critical values. According to the best critical values of EBVCL and TVRR, patients were stratified into low- and high-risk groups. Kaplan-Meier and ROC curve analyses were utilized to verify the prognostic ability of the new predictor (EBVCL+TVRR). The prognostic values among EBVCL+TVRR, EBVCL, TVRR, TNM stage, and the RECIST 1.1 criteria were compared by ROC curve. The primary end points were overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional failure-free survival (LRFFS). RESULTS: ROC curve analyses of TVRR on three-year survival showed the best critical values of TVRR was 32.72% for OS, 30.21% for PFS and LRFFS, 29.87% for DMFS. The best critical value of EBVCL was 127 copies/ml for OS, and 87.7 copies/ml for PFS, DMFS, and LRFFS. The three-year OS, PFS, DMFS, and LRFFS for low- and high-risk groups were 97.7% versus 78.3% (hazard ratio [HR] = 0.2398; 95% confidence interval [CI]: 0.1277-0.4502; p < 0.0001), 91.1% versus 60.9% (HR = 0.3294; 95% CI: 0.2050-0.5292; p < 0.0001), 94.2% versus 68.7% (HR = 0.2413; 95% CI: 0.1284-0.4535; p < 0.0001) and 97.8% versus 77.9% (HR = 0.3078; 95% CI: 0.1700-0.5573; p = 0.0001), respectively. The maximal area under ROC curve of EBVCL+TVRR, EBVCL, TVRR, TNM stage, and RECIST 1.1 criteria for three-year OS was 0.829, 0.750, 0.711, 0.555, and 0.605, respectively. CONCLUSION: The new-developed indicator (EBVCL+TVRR) could better predict the LANPC patient's survival after IC compared with TNM stage system or RECIST 1.1 criteria.

Survival and Trends in Annualized Hazard Function by Age at Diagnosis Among Chinese Breast Cancer Patients Aged ≤40 Years: Case Analysis Study.

BACKGROUND: Young breast cancer patients are more likely to develop aggressive tumor characteristics and a worse prognosis than older women, and different races and ethnicities have distinct epidemiologies and prognoses. However, few studies have evaluated the clinical biological features and relapse patterns in different age strata of young women in Asia. OBJECTIVE: We aimed to explore survival differences and the hazard function in young Chinese patients with breast cancer (BC) by age. METHODS: The patients were enrolled from West China Hospital, Sichuan University. The chi-squared test, a Kaplan-Meier analysis, a log-rank test, a Cox multivariate hazards regression model, and a hazard function were applied for data analysis. Locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), breast cancer-specific survival (BCSS), and overall survival (OS) were defined as end points. RESULTS: We included 1928 young BC patients diagnosed between 2008 and 2019. Patients aged 18 to 25, 26 to 30, 31 to 35, and 36 to 40 years accounted for 2.7% (n=53), 11.8% (n=228), 27.7% (n=535), and 57.7% (n=1112) of the patients, respectively. The diagnosis of young BC significantly increased from 2008 to 2019. Five-year LRFS, DMFS, BCSS, and OS for the entire population were 98.3%, 93.4%, 94.4%, and 94%, respectively. Patients aged 18 to 25 years had significantly poorer 5-year LRFS (P<.001), 5-year DMFS (P<.001), 5-year BCSS (P=.04), and 5-year OS (P=.04) than those aged 31 to 35, 26 to 30, and 36 to 40 years. The hazard curves for recurrence and metastasis for the whole cohort continuously increased over the years, while the BC mortality risk peaked at 2 to 3 years and then slowly decreased. When stratified by age, the annualized hazard function for recurrence, metastasis, and BC mortality in different age strata showed significantly different trends, especially for BC mortality. CONCLUSIONS: The annual diagnosis of young BC seemed to increase in Chinese patients, and the distinct age strata of young BC patients did not differ in survival outcome or failure pattern. Our results might provide strategies for personalized management of young BC.

Individualized 3D-printed bolus promotes precise postmastectomy radiotherapy in patients receiving breast reconstruction.

Purpose: To evaluate the efficacy and safety of 3D-printed tissue compensations in breast cancer patients receiving breast reconstruction and postmastectomy radiotherapy (PMRT). Methods and materials: We enrolled patients with breast cancer receiving breast reconstruction and PMRT. The dose distribution of target and skin, conformability, and dose limit of organs at risk (OARs) were collected to evaluate the efficacy of the 3D-printed bolus. Radiation Therapy Oncology Group (RTOG) radiation injury classification was used to evaluated the skin toxicities. Results: A total of 30 patients diagnosed between October 2019 to July 2021 were included for analysis. Among all the patients, the 3D-printed bolus could ensure the dose coverage of planning target volume (PTV) [homogeneity index (HI) 0.12 (range: 0.08-0.18)], and the mean doses of D99%, D98%, D95%, D50%, D2% and Dmean were 4606.29cGy, 4797.04cGy, 4943.32cGy, 5216.07cGy, 5236.10cGy, 5440.28cGy and 5462.10cGy, respectively. The bolus demonstrated an excellent conformability, and the mean air gaps between the bolus and the chest wall in five quadrants were 0.04cm, 0.18cm, 0.04cm, 0.04cm and 0.07cm, respectively. In addition, the bolus had acceptable dosage limit of OARs [ipsilateral lung: Dmean 1198.68 cGy, V5 46.10%, V20 21.66%, V30 16.31%); heart: Dmean 395.40 cGy, V30 1.02%, V40 0.22%; spinal cord planning risk volume (PRV): Dmax 1634 cGy] and skin toxicity (grade 1, 76.0%; grade 2, 21.0%; grade 3, 3.3%). Conclusion: The 3D-printed bolus offers advantages in terms of dose uniformity and controllable skin toxicities in patients receiving breast reconstruction and PMRT. Further research is needed to comprehensively evaluate the effectiveness of the 3Dprinted bolus in this patient subset.

The Value of the 8th Edition of American Joint Committee on Cancer Pathological Prognostic Staging on the Selection of Postmastectomy Radiotherapy for T1-2N1 Breast Cancer.

Methods and Materials: Patients diagnosed with pT1-2N1M0 breast cancer between 2008 and 2018 in West China Hospital, Sichuan University were included. Locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS) were defined as endpoints. The propensity score matching (PSM), receiver operating characteristic (ROC) curve, the Kaplan-Meier analysis, and the Cox multivariable model were used for data analysis. Results: We identified 1,615 patients with T1-2N1M0 breast cancer, and 44.9% (n = 744) of them were treated with PMRT. With a median follow-up of 76 months, 46 (2.8%) recurrences, 96 (5.9%) deaths, and 80 (5.0%) breast cancer-related deaths occurred. The 5-year LRFS, DMFS, DFS, BCSS, and OS were 98.6%, 95.3%, 93.7%, 96.5%, and 96.0%, respectively. PMRT could not improve 5-year LRFS, DMFS, DFS, BCSS, and OS compared with non-PMRT neither before nor after PSM in the era of contemporary systemic treatment. ROC curve showed that the 8th pathological prognostic staging had better discriminative ability compared with the 7th anatomical staging [the area under the curve (AUC) 0.653 vs. 0.546, P < 0.001]. In the anatomical staging system, PMRT had comparable 5-year BCSS in comparison with non-PMRT both in stages IIA (97.4% vs. 96.8%, P = 0.799) and IIB (95.3% vs. 97.0%, P = 0.071). When stratified according to the pathological staging, PMRT was associated with better 5-year BCSS in stage IIB (97.1% vs. 90.7%, P = 0.039), while not in stages IA, IB, IIA, and IIIA. Multivariate analysis demonstrated that PMRT was a significantly protective factor for BCSS in stage IIB (HR 0.331, 95% CI: 0.100-0.967, P = 0.044). Conclusion: The new staging could better select high-risk patients with T1-2N1 breast cancer for radiotherapy compared with the 7th staging, and PMRT might be exempted except the 8th staging of IIB in the era of contemporary systemic therapy in this disease.

The comparison of prognostic value of tumour volumetric regression ratio and RECIST 1.1 criteria after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: To compare the prognostic value of the sum volumetric regression ratio (SVRR) of the primary tumour and metastatic lymph nodes with treatment response based on RECIST 1.1 criteria after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: A total of 117 stage III-IVA NPC patients treated with induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) were retrospectively reviewed. The SVRR and the treatment response based on RECIST 1.1 were measured using contrast-enhanced computed tomography (CT) localisations before and after induction chemotherapy. The receiver operating characteristic (ROC) curve analysis was used to identify the optimal cutoff point of the SVRR and compare the prognostic value of the SVRR and RECIST 1.1criteria. RESULTS: The optimal cutoff points of SVRR for progression-free survival (PFS), locoregional failure-free survival (LRFFS) and distant metastasis-free survival (DMFS) were all 25.15%, while for overall survival (OS) it was 16.63%. The area under the ROC curve (AUC) of optimal cutoff points of SVRR was superior than that of RECIST 1.1 for PFS (AUC: 0.716 vs. 0.578; P = 0.0022), LRFFS (AUC: 0.700 vs. 0.574; P = 0.0080) and DMFS (AUC: 0.736 vs. 0.606; P = 0.0053), respectively. The 3-year PFS, DMFS and OS rates for SVRR less than vs. greater than or equal to the cutoff points were 55.8% vs. 92.2% (P < 0.001, hazard ratio (HR): 0.209, 95% confidence interval (CI): 0.091-0.480), 59.7% vs. 96.7% (P < 0.001, HR: 0.120, 95% CI: 0.043-0.336) and 66.7% vs. 98.1% (P < 0.001, HR: 0.069, 95% CI: 0.014-0.342), while the responses [stable disease (SD), partial response (PR)] based on RECIST 1.1 were not significantly associated with 3-year survival rates. Multivariate analysis indicated that SVRR was an independent prognostic factor for PFS, DMFS and OS (all P < 0.05). CONCLUSIONS: The sum volumetric regression ratio and response based on RECIST 1.1 were related to the prognosis in locoregionally advanced NPC after induction chemotherapy. Sum volumetric regression ratio is an independent outcome predictor for survival in locoregionally advanced NPC, playing a better prognostic role than RECIST 1.1.

Primary radical hysterectomy vs chemoradiation for IB2-IIA cervical cancer: A systematic review and meta-analysis.

BACKGROUND: To compare the clinical outcomes of radical hysterectomy (RH) with chemoradiotherapy (CRT) in women with stage IB2-IIA cervical cancer. METHODS: Based on articles published up to December 2017, a literature search of PubMed, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese National Knowledge Infrastructure (CNKI) databases was conducted to identify eligible studies. Overall survival (OS), progression-free survival (PFS) with hazard ratios (HRs), and toxicities with odds ratios (ORs) were analyzed. RESULTS: In total, 7 studies comprising 687 patients were identified for this meta-analysis. RH showed a significant trend toward improved survival outcomes compared with those of CRT, regardless of OS (HR = 0.49, 95% confidence interval [CI] 0.36-0.67, P < .001); or PFS (1.61, 95% CI 1.15-2.26, P = .005) for IB2-IIA cervical cancer. Subgroup analysis revealed that stage IB2 cervical cancer patients obtained better OS (HR = 0.36, 95% CI 0.23-0.56, P < .001; heterogeneity: P = .32, I = 13%). However, a higher incidence of grade 3/4 genitourinary abnormalities was evident with RH (OR = 2.3, 95% CI 1.42-3.87, P = .021). CONCLUSION: Our study suggested that RH had distinct advantages over CRT for carcinoma of the uterine cervix with FIGO stage IB2-IIA, especially for IB2 cervical cancer.

The prognostic value of volumetric reduction of the target lesions after induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: We explored whether the volumetric reduction ratio of target lesion after induction chemotherapy (IC) had any prognostic value in nasopharyngeal carcinoma (NPC). METHODS: From 2013 to 2016, 72 NPC patients treated with PCF (paclitaxel, cisplatin, 5-fluorouracil) IC followed by cisplatin-based concurrent chemoradiotherapy were analyzed. The volumes of target lesions before and after IC and survival conditions were assessed. RESULTS: For all cases, volumetric reduction ratios of the total tumor load ≥ optimal cutoff values were significantly associated with increased 2-year progression-free survival, locoregional failure-free survival, and distant metastasis-free survival (DMFS) rates, and for cervical lymph nodes, the volumetric reduction ratio ≥ optimal cutoff value was significant for DMFS (all P < .05). Accordingly, the optimal cutoff values were 24.56% (AUC = 60.5%), 23.91% (AUC = 57.7%), 29.77% (AUC = 75.8%), and 34.17% (AUC = 62.5%), respectively. CONCLUSION: Volumetric reductions of target lesions after IC are independent survival predictors for NPC, especially for those with N2/N3 disease.