Risk Of Locoregional Recurrence Research Articles

History of dysplasia and primary site associated with recurrence in T1N0 oral squamous cell carcinoma

Recurrent disease occurs in a significant proportion of early-stage oral squamous cell carcinoma (OSCC) despite removal of the entire tumor with clear surgical margins. Our study sought to identify clinicopathologic factors that increase the risk of locoregional recurrence in T1N0 OSCC. We conducted an observational retrospective analysis of 65 cases of T1N0 OSCC over a period of 13 years. For each case, we examined the clinical presentation, histopathologic appearance, and treatment characteristics of interest to evaluate the association between these variables and locoregional recurrence. The 5-year and 10-year locoregional recurrence rates were 29.2% and 33.8%, respectively. Individuals with prior oral dysplasia had significantly higher odds for locoregional recurrence (P < .01) and reduced 5-year disease-free survival rates (P < .01). OSCC of the tongue and floor of the mouth had lower recurrence odds than carcinomas of the gingiva, buccal mucosa, and palate (P < .05). Histologic grade (P=.80), depth of invasion (P=.82), and elective neck dissection (P=.80) did not appear to influence locoregional recurrence for T1N0 tumors. Given the morbidity and mortality associated with OSCC, understanding of the clinicopathologic factors associated with recurrent disease may lead to improved treatment and follow-up protocols for a subset of early-stage patients.

Predictors of Locoregional Recurrence and Delineation of Adjuvant Radiation Therapy Fields for Patients With Upper Tract Urothelial Carcinoma Receiving Nephroureterectomy

PurposeTo identify factors predictive of locoregional recurrence (LRR) in upper tract urothelial carcinoma (UTUC) treated with nephroureterectomy and to propose adjuvant radiation therapy (ART) fields. Methods and MaterialsClinical and pathologic variables for patients receiving nephroureterectomy for UTUC between 1995 and 2009 were analyzed for associations with outcomes. Sites of LRR from all patients with available imaging (39) were contoured on computed tomography image sets of patients with representative anatomy, and ART fields were proposed based on these distributions. ResultsA total of 279 patients with a median follow-up of 13.0 years were analyzed. The 5-year cumulative incidence of LRR was 16.7% (95% CI, 12.2-21). Pathologic risk factors (PRFs) associated with increased risk of LRR included tumor in both the renal pelvis and ureter, T stage ≥2, lymph node involvement, grade 3 histology, and positive surgical margins (P < .05). Patients with an increased number of PRFs had a significantly greater risk of LRR. The 5-year cumulative incidence estimates of LRR were 5.3% (95% CI, 1.8%-16.0%), 15.6% (95% CI, 9.5%-25.7%), and 43.9% (95% CI, 31.1%-62.1%) for those with 1, 2, and ≥3 PRFs, respectively. ART fields covering the renal fossa and retroperitoneal lymph nodes from the superior border of L1 through the aortic bifurcation would encompass all sites of LRR for 33 of 46 patients (72%). Non-LRR bladder and distant failure occurred in 101 (36.2%) and 73 (26.2%) of the patients, respectively. The 5-year cumulative incidence estimate of distant failure was 22.5% (95% CI, 17.4%-27.3%). ConclusionsIn patients receiving nephroureterectomy for UTUC, LRR is significantly increased in patients with 2 or more PRFs. These data provide clinically valuable insight into the selection of candidates for ART and the design of ART fields.

Intensity modulated radiotherapy for anal canal squamous cell carcinoma: A 16-year single institution experience

IntroductionTo report long-term efficacy and adverse events (AEs) associated with intensity modulated radiotherapy (IMRT) for patients with anal canal squamous cell carcinoma (ASCC). Materials and methodsThis was a retrospective review of patients with ASCC who received curative-intent IMRT and concurrent chemotherapy (98%) between 2003 and 2019. Overall survival (OS), colostomy-free survival (CFS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The cumulative incidence of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. Acute and late AEs were recorded per National Cancer Institute Common Terminology Criteria for AEs. Results127 patients were included. The median patient age was 63 years (interquartile range [IQR] 55–69) and 79% of patients were female. 33% of patients had T3-4 disease and 68% had clinically involved pelvic or inguinal lymph nodes (LNs).The median patient follow-up was 47 months (IQR: 28–89 months). The estimated 4-year OS, CFS, and PFS were 81% (95% confidence interval [CI]: 73%–89%), 77% (95% CI: 68%–86%), and 78% (95% CI: 70%–86%), respectively. The 4-year cumulative incidences of LR, LRR, and DM were 3% (95% CI: 1%–9%), 9% (95% CI: 5%–17%), and 10% (95% CI: 6%–18%), respectively. Overall treatment duration greater than 39 days was associated with an increased risk of LRR (Hazard Ratio [HR]: 5.2, 95% CI: 1.4–19.5, p = 0.015). The most common grade 3+ acute AEs included hematologic (31%), gastrointestinal (GI) (17%), dermatologic (16%), and pain (15%). Grade 3+ late AEs included: GI (3%), genitourinary (GU) (2%), and pain (1%). Current smokers were more likely to experience grade 3+ acute dermatologic toxicity compared to former or never smokers (34% vs. 7%, p < 0.001). ConclusionsIMRT was associated with favorable toxicity rates and long-term efficacy. These data support the continued utilization of IMRT as the preferred treatment technique for patients with ASCC.

Individual learning curve of cytoreductive surgery for peritoneal metastasis from colorectal cancer: A process with an impact on survival

BackgroundThis study aimed to assess the learning curve (LC) of cytoredutive surgery (CRS) of peritoneal metastasis (PM) from colorectal cancer (CRC). Information about learning curves is important for developing teaching tools and well-structured training programs for the implementation of this complex procedure in new healthcare centers. The aim of this study was to estimate how many procedures an inexperienced surgeon must perform (the length of the learning period) in order to demonstrate an acceptably low rate of locoregional recurrence. MethodsAll consecutive 74 patients with CRS for CRC performed by a novice surgeon between 2012 and 2017 in a tertiary cancer center were included. The learning curve was calculated by a cumulative sum control chart (CUSUM) graph. Two groups were formed based on the length of the learning period and were compared on overall and disease free survival. ResultsThe risk of locoregional recurrence decreased after surgeons had performed 19 cases, suggesting a learning period of this length. Overall survival and postoperative morbidity were not significantly different between learning and proficiency periods. Multiple linear regression analysis showed that the learning period and peritoneal cancer index are the only factors affecting disease free survival. A second learning period was observed in cases where patient care became more complex. ConclusionsThis study confirms that learning period has negative impacts on disease-free survival. An initial experience supervised in specialized centers allow to have a short learning curve for CRS for peritoneal metastases for CRC.

Abstract PS6-10: Risk estimation of locoregional recurrence, distant metastasis and second primary breast cancer in early stage breast cancer patients: The INFLUENCE 2.0 nomogram

Abstract Background Breast cancer follow-up aims at early detection of locoregional recurrences (LRR) and second primary breast cancer (SP). Predicting a patient’s time-dependent risk for such an event may improve follow-up strategies. Furthermore, many clinicians and patients are interested in the risk of distant metastasis (DM) as well, as it provides additional information on prognosis. The existing INFLUENCE nomogram predicts the yearly risk of LRR up to five years from diagnosis using logistic regression analyses. However, this model was based on patients diagnosed between 2003 and 2006 and lacked information on HER2 status, which is nowadays an important prognostic variable. In this population-based study, we aimed to improve the INFLUENCE model with more flexible predictions over time, more recent information and additional outcomes - risk of LRR, distant metastasis (DM) and SP - using different underlying models. Methods Patient-, tumor- and treatment-related characteristics of all female patients diagnosed with invasive adenocarcinoma of the breast in 2007, 2008 and 2012, of who active 5-year follow-up was performed, were selected from the Netherlands Cancer Registry. Models were developed for LRR, DM and SP as a first event separately, and for each three-monthly time interval to predict time-dependent risks as accurately as possible. Follow-up was calculated from date of definite surgery to date of event or last observation. We compared three different models to estimate the three outcomes: a Cox regression model, a flexible parametric spline model and a random survival forest (RF) model. To assess calibration of each outcome, three-monthly risk predictions during the 5-year follow-up period were compared to corresponding observed event rates. To assess discrimination, the areas under the curves (AUC) were calculated for each timeframe in the 5-year period and averaged to one combined measure (average 5-year AUC). To correct for optimism we performed bootstrapping on the entire cohort with 200 replicates and updated the calibration measures and AUCs accordingly. Results In total, 13,494 patients were included. LRR, DM and SP within five years were experienced by 2.8%, 6.3% and 3.1% of the patients, respectively. The following variables were included in the final models: age, tumor grade, tumor stage, nodal stage, multifocality, HER2 status, hormonal receptor status, type of surgery, chemotherapy, radiotherapy, hormonal therapy, anti-HER2 therapy. The optimism-corrected mean time-dependent prediction errors for individual risk predictions ranged between 0.12% and 0.46% for all three models and all three month timeframes. The average 5-year AUCs for LRR, SP and DM using the Cox model were 0.71, 0.63 and 0.77, respectively. The average 5-year AUCs for LRR, SP and DM using the parametric spline model were 0.71, 0.63 and 0.78, respectively. When using the RF model, the average 5-year AUCs were 0.74, 0.68 and 0.77 for LRR, SP and DM, respectively (Table). Conclusion Although differences were very small, the RF model had the best performance overall. This INFLUENCE 2.0 model provides us with updated information on the individual time-dependent risks of LRR, DM and SP within five years following surgery. This model is freely accessible at https://tinyurl.com/influence-2 and can be used as an instrument to improve follow-up strategies and to give patients better insights in their prognosis. Table. Optimism-corrected average AUCs over the 5-year follow-up periodModel typeLRDMSPCox regression0.710.770.63Flexible parametric spline0.710.780.63Random survival forest0.740.770.68 Citation Format: Sabine Siesling, Vinzenz Völkel, Tom Hueting, Teresa Draeger, Marissa C van Maaren, Luc JA Strobbe, Marjanka K Schmidt, Gabe S Sonke, Marjan van Hezewijk, Catharina GM Groothuis-Oudshoorn. Risk estimation of locoregional recurrence, distant metastasis and second primary breast cancer in early stage breast cancer patients: The INFLUENCE 2.0 nomogram [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-10.

Postoperative Management of Salivary Gland Tumors.

Salivary gland tumors represent a heterogeneous group of neoplasms characterized by varied histologies and disease outcomes. Initial treatment for the primary and gross nodal disease is usually surgery. Management of the clinically node-negative neck depends upon the risk of lymph nodal involvement. This is usually determined by the AJCC "T" stage and histology. Both surgery and radiation may be utilized to address the lymph nodes at risk. This is especially important for minor salivary gland tumors. Radiation plays an important role in the adjuvant management of salivary gland tumors by reducing the risk of locoregional recurrence. Certain histologies like adenoid cystic carcinoma have a predilection for neurotropic spread to the skull base. Radiation is particularly important in controlling disease at the skull base. The role of concurrent chemotherapy in the adjuvant treatment of salivary gland tumors is not established and remains an area of active research. Certain histologies like salivary duct carcinoma exhibit readily identifiable molecular targets amenable to targeted therapy. Finally, advanced testing of these tumors using next-generation sequencing can also potentially identify molecular targets amenable to therapy. While useful in the management of metastatic disease, the role of these therapies in the adjuvant setting remains unknown.

Patterns of recurrence following definitive chemoradiation for patients with proximal esophageal cancer

IntroductionThe aim of this retrospective study was to determine the patterns of recurrence and overall survival (OS) in patients achieving clinical complete response after treatment with definitive chemoradiation (CRT) for proximal esophageal cancer. Materials and methodsPatients with proximal esophageal cancer treated with CRT between 2004 and 2014 in 11 centers in the Netherlands were included. OS and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Cumulative incidence of first recurrence (locoregional or distant) and locoregional recurrence (LRR) were assessed using competing risk analyses. ResultsIn 197 of the 200 identified patients, response was evaluated, 133 (68%) showed a complete response. In complete responders, median OS, three-year OS, and PFS were 45.0 months (95% CI 34.8–61.5 months), 58% (95% CI 48–66), and 49% (95% CI 40–57), respectively. Three- and five-year risk of recurrence were respectively 40% (95% CI 31–48), and 45% (95% CI 36–54). Three- and five-year risk of LRR were 26% (95% CI 19–33), and 30% (95% CI 22–38). Eight of 32 patients with an isolated LRR underwent salvage surgery, with a median OS of 32.0 months (95% CI 6.8-not reached). ConclusionIn patients with a complete response after definitive CRT for proximal esophageal cancer, most recurrences were locoregional and developed within the first three years after CRT. These findings suggest to shorten locoregional follow-up from five to three years.

Combined breast conservation therapy versus mastectomy for BRCA mutation carriers – A systematic review and meta-analysis

BackgroundThe non-inferiority of combined breast conservation surgery (BCS) and radiotherapy (breast conservation therapy or BCT) compared to mastectomy in sporadic breast cancer cases is well recognised. Uncertainty remains regarding optimal surgical practice in BRCA mutation carriers. AimsTo evaluate the oncological safety of combined BCT versus mastectomy in BRCA mutation carriers following breast cancer diagnosis. MethodsA systematic review was performed as per PRISMA and MOOSE guidelines. Observational studies comparing BCS and mastectomy in BRCA carriers were identified. Dichotomous variables were pooled as odds ratios (OR) using the Mantel–Haenszel method. Log hazard ratios (lnHR) for locoregional recurrence (LRR), contralateral breast cancer, disease-free and overall survival and their standard errors were calculated from Kaplan-Meier or cox-regression analyses and pooled using the inverse variance method. ResultsTwenty three studies of 3807 patients met inclusion criteria; 2200 (57.7%) were BRCA1 and 1212 (31.8%) were BRCA2 carriers. Median age at diagnosis was 41 years with 96 months follow up. BCS was performed on 2157 (56.7%) while 1408 (41.5%) underwent mastectomy. An increased risk of LRR was observed in patients treated with BCS (HR:4.54, 95% Confidence Interval: 2.77–7.42, P < 0.001, heterogeneity (I2) = 0%). However, the risks of contralateral breast cancer (HR:1.51, 95%CI: 0.44–5.11, P = 0.510, I2 = 80%), disease recurrence (HR:1.16, 95%CI: 0.78–1.72, P = 0.470, I2 = 44%), disease-specific recurrence (HR:1.58, 95%CI: 0.79–3.15, P = 0.200, I2 = 38%) and death (HR:1.10, 95%CI: 0.72–1.69, P = 0.660, I2 = 38%) were equivalent for combined BCT and mastectomy. ConclusionsSurvival outcomes following combined BCT is comparable to mastectomy in BRCA carriers. However, the risk of LRR is increased. Patient counselling should be tailored to incorporate these findings.

Hypofractionated radiotherapy in locally advanced bladder cancer: an individual patient data meta-analysis of the BC2001 and BCON trials.

SummaryBackgroundTwo radiotherapy fractionation schedules are used to treat locally advanced bladder cancer: 64 Gy in 32 fractions over 6·5 weeks and a hypofractionated schedule of 55 Gy in 20 fractions over 4 weeks. Long-term outcomes of these schedules in several cohort studies and case series suggest that response, survival, and toxicity are similar, but no direct comparison has been published. The present study aimed to assess the non-inferiority of 55 Gy in 20 fractions to 64 Gy in 32 fractions in terms of invasive locoregional control and late toxicity in patients with locally advanced bladder cancer.MethodsWe did a meta-analysis of individual patient data from patients (age ≥18 years) with locally advanced bladder cancer (T1G3 [high-grade non-muscle invasive] or T2–T4, N0M0) enrolled in two multicentre, randomised, controlled, phase 3 trials done in the UK: BC2001 (NCT00024349; assessing addition of chemotherapy to radiotherapy) and BCON (NCT00033436; assessing hypoxia-modifying therapy combined with radiotherapy). In each trial, the fractionation schedule was chosen according to local standard practice. Co-primary endpoints were invasive locoregional control (non-inferiority margin hazard ratio [HR]=1·25); and late bladder or rectum toxicity, assessed with the Late Effects Normal Tissue Task Force-Subjective, Objective, Management, Analytic tool (non-inferiority margin for absolute risk difference [RD]=10%). If non-inferiority was met for invasive locoregional control, superiority could be considered if the 95% CI for the treatment effect excluded the null effect (HR=1). One-stage individual patient data meta-analysis models for the time-to-event and binary outcomes were used, accounting for trial differences, within-centre correlation, randomised treatment received, baseline variable imbalances, and potential confounding from relevant prognostic factors.Findings782 patients with known fractionation schedules (456 from the BC2001 trial and 326 from the BCON trial; 376 (48%) received 64 Gy in 32 fractions and 406 (52%) received 55 Gy in 20 fractions) were included in our meta-analysis. Median follow-up was 120 months (IQR 99–159). Patients who received 55 Gy in 20 fractions had a lower risk of invasive locoregional recurrence than those who received 64 Gy in 32 fractions (adjusted HR 0·71 [95% CI 0·52–0·96]). Both schedules had similar toxicity profiles (adjusted RD −3·37% [95% CI −11·85 to 5·10]).InterpretationA hypofractionated schedule of 55 Gy in 20 fractions is non-inferior to 64 Gy in 32 fractions with regard to both invasive locoregional control and toxicity, and is superior with regard to invasive locoregional control. 55 Gy in 20 fractions should be adopted as a standard of care for bladder preservation in patients with locally advanced bladder cancer.FundingCancer Research UK.

Breast conservation among older patients with early-stage breast cancer: Locoregional recurrence following adjuvant radiation or hormonal therapy.

For patients with breast cancer undergoing breast-conserving surgery (BCS), adjuvant radiation (RT) and hormonal therapy (HT) reduce the risk of locoregional recurrence (LRR). Although several studies have evaluated adjuvant HT ± RT, the outcomes of HT versus RT monotherapy remain less clear. In this study, the risk of LRR is characterized among older patients with early-stage breast cancer following adjuvant RT alone, HT alone, neither, or both. This study included female patients from the Memorial Sloan Kettering Cancer Center (New York, New York) who were aged ≥65 years with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) T1N0 breast cancer treated with BCS. The primary endpoint was time to LRR evaluated by Cox regression analysis. There were 888 women evaluated with a median age of 71 years (range, 65-100 years) and median follow-up of 4.9 years (range, 0.0-9.5 years). There were 27 LRR events (3.0%). Five-year LRR was 11% for those receiving no adjuvant treatment, 3% for HT alone, 4% for RT alone, and 1% for HT and RT. LRR rates were significantly different between the groups (P < .001). Compared with neither HT nor RT, HT or RT monotherapy each yielded similar LRR reductions: HT alone (HR, 0.27; 95% CI, 0.10-0.68; P = .006) and RT alone (HR, 0.32; 95% CI, 0.11-0.92; P = .034). Distant recurrence and breast cancer-specific survival rates did not significantly differ between groups. LRR risk following BCS is low among women aged ≥65 years with T1N0, ER+/HER2- breast cancer. Adjuvant RT and HT monotherapy each similarly reduce this risk; the combination yields a marginal improvement. Further study is needed to elucidate whether appropriate patients may feasibly receive adjuvant RT monotherapy versus the current standards of HT monotherapy or combined RT/HT.

Dental management in palliative care of a patient with advanced oral cancer

Tongue squamous cell carcinoma is one of the most prevalent and aggressive head and neck carcinomas. When diagnosed in an advanced stage is associated with a reduced overall survival rate due to the increased risk of locoregional recurrence and distant metastases. This article discusses the dental care strategies that were adopted regarding the progression to an incurable state of a 52-year-old man diagnosed with advanced tongue squamous cell carcinoma, which was initially treated with exclusive radiotherapy. In a 5-year-period, this patient developed severe lesions of osteoradionecrosis and also local tumor recurrence without the possibility of curative treatment. Palliative care in the dental context must be adopted in order to provide physical and emotional health still at the final moments in the patient’s life.

Recurrence risk stratification based on a competing-risks nomogram to identify patients with esophageal cancer who may benefit from postoperative radiotherapy.

Background:A reliable model is needed to estimate the risk of postoperative recurrence and the benefits of postoperative radiotherapy (PORT) in patients with thoracic esophageal squamous cell cancer (TESCC).Methods:The study retrospectively reviewed 3652 TESCC patients in stage IB-IVA after radical esophagectomy, with or without PORT. In one institution as the training cohort (n = 1620), independent risk factors associated with locoregional recurrence (LRR), identified by the competing-risks regression, were used to establish a predicting nomogram, which was validated in an external cohort (n = 1048). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate discrimination. Risk stratification was conducted using a decision tree analysis based on the cumulative point score of the LRR nomogram. After balancing the baseline of characteristics between treatment groups by inverse probability of treatment weighting, the effect of PORT was evaluated in each risk group.Results:Sex, age, tumor location, tumor grade, and N category were identified as independent risk factors for LRR and added into the nomogram. The AUC values were 0.638 and 0.706 in the training and validation cohorts, respectively. Three risk groups were established. For patients in the intermediate- and high-risk groups, PORT significantly improved the 5-year overall survival by 10.2% and 9.4%, respectively (p < 0.05). Although PORT was significantly associated with reduced LRR in the low-risk group, overall survival was not improved.Conclusion:The nomogram can effectively estimate the individual risk of LRR, and patients in the intermediate- and high-risk groups are highly recommended to undergo PORT.

Nomogram Predicting the Risk of Locoregional Recurrence After Mastectomy for Invasive Micropapillary Carcinoma of the Breast

BackgroundThe risk of locoregional recurrence (LRR) after mastectomy for breast invasive micropapillary carcinoma (IMPC) remains poorly defined. We aimed to construct an effective prognostic nomogram to estimate the individualized risk of LRR for providing accurate information for long-term follow-up. Patients and MethodsA total of 388 patients with breast IMPC were included in the current study. Based on the Cox regression and clinical significance, a nomogram with an online prediction version was created. This model was evaluated and internally validated by concordance index and calibration plot. Receiver operating characteristic curve and decision curve analysis were used to assess the discrimination and clinical utility, and Kaplan-Meier curves estimated the probability of LRR. ResultsThe variables (age, lymph node metastasis, hormone receptor status, lymphovascular invasion, histologic grade, and adjuvant radiotherapy) were included in the nomogram. This model was well-calibrated to predict the possibility of LRR and displayed favorable clinical utility; the concordance index was 0.86 (95% confidence interval, 0.81-0.91), which was higher than any single predictor. The area under the curve of the nomogram was 0.89, whereas that of the conventional staging system was 0.72. An online prognostic nomogram was built for convenient use. Kaplan-Meier curves showed that the nomogram had a better risk stratification than the conventional staging system. ConclusionsThe nomogram could accurately predict the individualized risk of LRR after mastectomy for breast IMPC. By identifying the risk stratification, this model is expected to assist clinicians and patients in improving long-term follow-up strategies.

Short-term CDK4/6 Inhibition Radiosensitizes Estrogen Receptor-Positive Breast Cancers.

Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have improved progression-free survival for metastatic, estrogen receptor-positive (ER+) breast cancers, but their role in the nonmetastatic setting remains unclear. We sought to understand the effects of CDK4/6 inhibition (CDK4/6i) and radiotherapy in multiple preclinical breast cancer models. Transcriptomic and proteomic analyses were used to identify significantly altered pathways after CDK4/6i. Clonogenic assays were used to quantify the radiotherapy enhancement ratio (rER). DNA damage was quantified using γH2AX staining and the neutral comet assay. DNA repair was assessed using RAD51 foci formation and nonhomologous end joining (NHEJ) reporter assays. Orthotopic xenografts were used to assess the efficacy of combination therapy. Palbociclib significantly radiosensitized multiple ER+ cell lines at low nanomolar, sub IC50 concentrations (rER: 1.21-1.52) and led to a decrease in the surviving fraction of cells at 2 Gy (P < 0.001). Similar results were observed in ribociclib-treated (rER: 1.08-1.68) and abemaciclib-treated (rER: 1.19-2.05) cells. Combination treatment decreased RAD51 foci formation (P < 0.001), leading to a suppression of homologous recombination activity, but did not affect NHEJ efficiency (P > 0.05). Immortalized breast epithelial cells and cells with acquired resistance to CDK4/6i did not demonstrate radiosensitization (rER: 0.94-1.11) or changes in RAD51 foci. In xenograft models, concurrent palbociclib and radiotherapy led to a significant decrease in tumor growth. These studies provide preclinical rationale to test CDK4/6i and radiotherapy in women with locally advanced ER+ breast cancer at high risk for locoregional recurrence.

Effect of Capecitabine Maintenance Therapy Using Lower Dosage and Higher Frequency vs Observation on Disease-Free Survival Among Patients With Early-Stage Triple-Negative Breast Cancer Who Had Received Standard Treatment

Among all subtypes of breast cancer, triple-negative breast cancer has a relatively high relapse rate and poor outcome after standard treatment. Effective strategies to reduce the risk of relapse and death are needed. To evaluate the efficacy and adverse effects of low-dose capecitabine maintenance after standard adjuvant chemotherapy in early-stage triple-negative breast cancer. Randomized clinical trial conducted at 13 academic centers and clinical sites in China from April 2010 to December 2016 and final date of follow-up was April 30, 2020. Patients (n = 443) had early-stage triple-negative breast cancer and had completed standard adjuvant chemotherapy. Eligible patients were randomized 1:1 to receive capecitabine (n = 222) at a dose of 650 mg/m2 twice a day by mouth for 1 year without interruption or to observation (n = 221) after completion of standard adjuvant chemotherapy. The primary end point was disease-free survival. Secondary end points included distant disease-free survival, overall survival, locoregional recurrence-free survival, and adverse events. Among 443 women who were randomized, 434 were included in the full analysis set (mean [SD] age, 46 [9.9] years; T1/T2 stage, 93.1%; node-negative, 61.8%) (98.0% completed the trial). After a median follow-up of 61 months (interquartile range, 44-82), 94 events were observed, including 38 events (37 recurrences and 32 deaths) in the capecitabine group and 56 events (56 recurrences and 40 deaths) in the observation group. The estimated 5-year disease-free survival was 82.8% in the capecitabine group and 73.0% in the observation group (hazard ratio [HR] for risk of recurrence or death, 0.64 [95% CI, 0.42-0.95]; P = .03). In the capecitabine group vs the observation group, the estimated 5-year distant disease-free survival was 85.8% vs 75.8% (HR for risk of distant metastasis or death, 0.60 [95% CI, 0.38-0.92]; P = .02), the estimated 5-year overall survival was 85.5% vs 81.3% (HR for risk of death, 0.75 [95% CI, 0.47-1.19]; P = .22), and the estimated 5-year locoregional recurrence-free survival was 85.0% vs 80.8% (HR for risk of locoregional recurrence or death, 0.72 [95% CI, 0.46-1.13]; P = .15). The most common capecitabine-related adverse event was hand-foot syndrome (45.2%), with 7.7% of patients experiencing a grade 3 event. Among women with early-stage triple-negative breast cancer who received standard adjuvant treatment, low-dose capecitabine maintenance therapy for 1 year, compared with observation, resulted in significantly improved 5-year disease-free survival. ClinicalTrials.gov Identifier: NCT01112826.

The Significance of Neutrophil-to-Lymphocyte Ratio and Combined Chemoradiotherapy in Patients Undergoing Bladder Preservation Therapy for Muscle-Invasive Bladder Cancer.

BackgroundBladder-sparing treatment has been developed with the aim of preserving bladder function. However, considerable controversy remains regarding the effectiveness of organ preservation strategies. Accordingly, we investigated factors influencing the prognosis of muscle-invasive bladder cancer (MIBC) patients who received bladder-sparing treatment.Materials and MethodsIn the study, we retrospectively reviewed 193 patients who were newly diagnosed with MIBC and received bladder-sparing treatment from 2006 to 2013 in our hospital.ResultsThe 5-year overall survival, progression-free survival (PFS) and bladder-preservation survival rates after diagnosis were 64.7%, 52.1%, and 64%, respectively. The presence of hydronephrosis, advanced stage and not achieving complete response were associated with a marked reduction in PFS. Treatment with an adequate dose of combined chemoradiotherapy (CCRT) (chemotherapy ≥2 cycles combined with radiotherapy dose ≥56Gy) significantly improved the complete response (CR), 5-year bladder-preservation survival, and PFS rates, particularly for patients with good performance status. The 5-year bladder-preservation survival rates for CR and non-CR patients were 75%, and 21%, respectively. Furthermore, higher pre-treatment neutrophil-to-lymphocyte ratio (NLR) (≥3) and lower hemoglobin (≤12) were significantly associated with lower CR rate, increased risk of loco-regional recurrence and reduced bladder-preservation survival rate. Multivariable Cox regression analysis based on different co-variables showed that pretreatment NLR was an independent prognostic factor for PFS when MIBC patients were stratified by clinical stage and the doses of CCRT.ConclusionIn MIBC patients with bladder-sparing treatment, adequate doses of CCRT and low NLR were found to be correlated with better PFS. We suggest the use of NLR as a clinical biomarker for the prognosis of MIBC and guidance of treatment decisions.

Definition and validation of a radiomics signature for loco-regional tumour control in patients with locally advanced head and neck squamous cell carcinoma

PurposeTo develop and validate a CT-based radiomics signature for the prognosis of loco-regional tumour control (LRC) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated by primary radiochemotherapy (RCTx) based on retrospective data from 6 partner sites of the German Cancer Consortium - Radiation Oncology Group (DKTK-ROG). Material and methodsPre-treatment CT images of 318 patients with locally advanced HNSCC were collected. Four-hundred forty-six features were extracted from each primary tumour volume and then filtered through stability analysis and clustering. First, a baseline signature was developed from demographic and tumour-associated clinical parameters. This signature was then supplemented by CT imaging features. A final signature was derived using repeated 3-fold cross-validation on the discovery cohort. Performance in external validation was assessed by the concordance index (C-Index). Furthermore, calibration and patient stratification in groups with low and high risk for loco-regional recurrence were analysed. ResultsFor the clinical baseline signature, only the primary tumour volume was selected. The final signature combined the tumour volume with two independent radiomics features. It achieved moderately good discriminatory performance (C-Index [95% confidence interval]: 0.66 [0.55–0.75]) on the validation cohort along with significant patient stratification (p = 0.005) and good calibration. ConclusionWe identified and validated a clinical-radiomics signature for LRC of locally advanced HNSCC using a multi-centric retrospective dataset. Prospective validation will be performed on the primary cohort of the HNprädBio trial of the DKTK-ROG once follow-up is completed.

Lateral pelvic lymphadenectomy for low rectal cancer: a META-analysis of recurrence rates.

Locoregional recurrence (LR) remains a problem for patients with lower rectal cancer despite standardized surgery and improved neoadjuvant treatment regimens. Lateral pelvic lymph node dissection (LPLND) has been routine practice for some time in the Orient/East, but other regions have concerns about morbidity. As perioperative care and surgical approaches are refined, this has been revisited for selected patients. The question as to whether LPLND improves oncological outcomes was explored here. A systematic review of patients who underwent TME with or without LPLND from 2000 to 2020 was performed. The primary endpoint was the rate of LR between the two groups. Seven papers met the predefined search criteria in which 2000 patients underwent TME alone, while 1563 patients had TME and LPLND. The rate of LR was marginally higher with TME alone when compared with TME plus LPLND, but this result was not statistically significant (9.8 vs 9.4%, odds ratio 0.75, 95% CI 0.41-1.38, *p =0.35). In addition, four studies reported on distant recurrence rates, with TME and LPLND showing a slight reduction in overall rates (27.3 vs 29.9%, respectively, OR 0.65, 95% CI 0.45-0.92, *p =0.02). The addition of LPLND to TME is not associated with a significantly lower risk of LR in patients who undergo surgery for lower rectal cancer.

Risk stratification for prediction of locoregional recurrence in patients with pathologic T1\u20132N0 breast cancer after mastectomy

BackgroundPrevious studies have revealed that nearly 15–20% of selected high-risk T1–2N0 breast cancers developed LRR after mastectomy. This study is aim to indentify the risk factors of locoregional recurrence (LRR) in patients with pathologic T1–2N0 breast cancer after mastectomy in a real-world and distinguish individuals who warrant postmastectomy radiotherapy (PMRT).MethodsFemale patients treated from 1999 to 2014 in National Cancer Center of China were retrospectively reviewed. A competing risk model was developed to estimate the cumulative incidence of LRR with death treated as a competing event.ResultsA total of 4841 patients were eligible. All underwent mastectomy plus axillary nodes dissection or sentinel node biopsy without PMRT. With a median follow-up of 56.4 months (range, 1–222 months), the 5-year LRR rate was 3.9%.Besides treatment era, age ≤ 40 years old (p < 0.001, hazard ratio [HR] = 2.262), tumor located in inner quadrant (p < 0.001, HR = 2.236), T2 stage (p = 0.020, HR = 1.419), and negative expressions of estrogen receptor (ER) and progesterone receptor (PR) (p = 0.032, HR = 1.485), were patients-related independent risk factors for LRR. The 5-year LRR rates were 1.7, 3.5, and 15.0% for patients with zero, 1–2, and 3–4 risk factors (p < 0.001).ConclusionsRisk Stratification based on age, T stage, ER/PR status and tumor location can stratify patients with pT1–2 N0 breast cancer into subgroups with different risk of LRR. PMRT might be suggested for patients with 3–4 risk factors.

Breast Conservation among Older, Early Stage Breast Cancer Patients: Locoregional Recurrence Following Adjuvant Radiation or Hormone Therapy

Following breast-conserving surgery (BCS), both radiation therapy (RT) and hormone therapy (HT) reduce the risk of locoregional recurrence (LRR) among favorable subgroups of breast cancer. Several studies have evaluated HT +/- RT, though local outcomes of HT versus RT monotherapy remain unclear. Indeed, many patients do not complete the full multi-year course of HT, yet little is known about LRR rates in absence of HT. Here, we evaluate rates of adjuvant HT and RT use in a cohort of favorable-risk patients over 65 years of age, and report LRR in the setting of adjuvant RT alone, HT alone, neither, or both. We analyzed a cohort of breast cancer patients ≥65 years of age with estrogen receptor positive (ER+), HER2/neu negative (HER2-) T1N0 breast cancer diagnosed between 2010 and 2015 and treated with BCS. Clinicopathologic features were collected including type of axillary surgery, RT modality, use of RT boost, duration of HT, chemotherapy, and OncotypeDx Recurrence Scores (RS). Cox regression analysis was conducted using time to LRR as the primary endpoint. A total of 1,016 women were included with a median age of 70 (IQR 67-75) and median follow-up of 4.9 years (range 0.4-7.7). Overall, 36 (4%) LRR events were observed and 16 (2%) patients had a distant recurrence. The 5-year overall survival rate for the cohort was 96%. A total of 624 (61%) patients received RT. While 894 (88%) were started on HT, 725 (72%) completed a full course or remain adherent at last follow-up. Evaluated by treatment group (with HT defined as fully compliant to date), 481 (48%) patients received both HT and RT (5-year LRR 2%, 95%CI 1-4%), 244 (24%) received HT alone (5-year LRR 4%, 95% CI 2-8%), 143 (14%) received RT alone (5-year LRR 5%, 95%CI 2-11%), and 142 (14%) received neither HT nor RT (LRR 11%, 95%CI 6-19%). LRR rates were significantly different between these four treatment groups (Log rank p<0.001). On Cox regression, accounting for clinicopathologic variables, lymphovascular invasion (HR 6.37, 95%CI 2.17-18.7; p<0.001) and adjuvant treatment group were significant predictors of LRR. Compared to neither HT nor RT, combination HT and RT was significantly associated with the greatest reduction in LRR (HR 0.11, 95%CI 0.04-0.29; p<0.001). HT or RT monotherapy each yielded similar reductions in LRR: HT alone (HR 0.28, 95%CI 0.11-0.71; p = 0.008) and RT alone (HR 0.29, 95%CI 0.10-0.84; p = 0.023). The risk of LRR following BCS is low among women ≥65 years of age with T1N0, ER+/HER2- breast cancer. RT and HT monotherapy each significantly reduce this risk to a similar extent. While the combination of RT and HT further reduces the risk of LRR in a statistically significant manner, the absolute benefit of this dual-approach is modest. Further study will elucidate whether appropriate patients may feasibly receive RT monotherapy rather than the current standards of HT monotherapy or dual RT and HT therapy.