Trimodality Therapy Research Articles

Is Tumor Regression Grade Sufficient to Predict Survival in Esophageal Cancer with Trimodal Therapy?

Background This study aimed to assess the predictive value of tumor regression grade (TRG) and nodal status on survival in esophageal carcinoma with neoadjuvant chemoradiotherapy (nCRT). Methods Tumor pathologic regression and nodal status were assessed. Differences in survival stratified by TRG or nodal status were analyzed using the Kaplan–Meier method and log–rank test. The prognostic value of TRG and nodal status were analyzed using univariate and multivariate Cox proportional hazards methods. Results From July 2016 to June 2019, 253 patients with esophageal cancer underwent nCRT followed by surgery. Significant differences were presented in survival according to nodal status but not TRG. Multivariate analysis showed that nodal status and not TRG was the only independent predicter for overall survival (HR: 3.550, 95% CI: 2.264–5.566, P < 0.001) and disease-free survival (HR: 2.801, 95% CI: 1.874–4.187, P < 0.001). The modified TRG system combining tumor regression with nodal status stratified patients survival with good discrimination. Conclusions Lymph node status impacts more importantly than TRG on survival for patients with esophageal cancer undergoing nCRT plus esophagectomy. The modified TRG system may facilitate postoperative treatment decisions and survival surveillance.

250. PROGNOSTIC FACTORS ASSOCIATED WITH 18FDG-PET/CT IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA AFTER TRIMODALITY TREATMENT

Abstract Patients with locally advanced and potentially curable esophageal cancer (EC) should receive trimodality treatment, which involves neoadjuvant concurrent chemoradiotherapy (nCRT) followed by esophagectomy. The maximum standard uptake value (SUVmax) in SUV of 18FDG-PET/CT have been reported to be useful in predicting the prognosis of EC patients treated with nCRT and subsequent esophagectomy. We aimed to determine the pathological response in patients with EC after trimodality therapy and to investigate the prognostic factors associated with SUVmax. This was a retrospective study of patients with locally advanced esophageal squamous cell carcinoma who received nCRT followed by esophagectomy between January 2011 and December 2018 at the Tri-Service General Hospital in Taipei, Taiwan. Survival analysis was performed using the Kaplan–Meier method and the Cox proportional hazards model. Univariate and multivariate analyses were used to determine the independent prognostic factors. A total of 79 patients with esophageal cancer underwent esophagectomy, and 50 of them were enrolled in the study. Among the 50 patients enrolled, 18 had a pCR. A post-nCRT maximum standard uptake value (SUVmax) ≥ 3 was a poor prognostic factor associated with OS (hazard ratio [HR]: 3.665, P = 0.013) and PFS (HR: 3.417, P = 0.011). Poor prognosis was found in patients with pCR and a post-nCRT SUVmax ≥3 as compared with those with pathological partial response and a post-nCRT SUVmax &amp;lt;3. SUVmax ≥3 is a poor prognostic factor in ESCC after trimodality treatment, even in patients with pCR.

En bloc radical cystectomy: An overview of the technique and oncological results.

To reduce recurrence after radical cystectomy (RC), we developed a technique based on the principles of the circumferential resection margin used during total mesorectal excision for rectal cancer, namely, en bloc radical cystectomy (EbRC). The study included all patients in Mid-Norway (population of 739 k) with high-grade superficial or muscle invasive bladder cancer considered for radical treatment according to European guidelines, from January 2012 to August 2021, except for three patients receiving trimodal therapy. One hundred forty-five patients were treated with EbRC and 188 patients with standard RC (stdRC). There were no exclusion criteria. Both groups included open and robot-assisted techniques. EbRC entails cystectomy with extended pelvic lymph node dissection. The technique focuses on systematic uninterrupted mobilisation of all lymphatic tissue from the circumferential resection margin towards the bladder pedicles, and resecting the tissue en bloc with the bladder. The 3-year recurrence-free survival (RFS) was 86% for EbRC versus 67% for stdRC. The hazard ratio for overall survival in multivariable cox regression analyses after EbRC versus stdRC was 0.30 (95% CI 0.16-0.57, p≤0.001). The improved outcomes persisted in propensity score-matched analyses. There were no differences in Clavien-Dindo 3 and 4 complications (12.4% vs. 11.7%), nor 90-day mortality (2.1% vs. 1.6%). Improved oncological results with EbRC versus stdRC mirror the historical data after total mesorectal excision was initiated over 35 years ago in rectal cancer surgery. EbRC is safe and the preliminary oncological results are promising.

Effect of Health Disparities on Refusal of Trimodality Therapy in Localized Esophageal Adenocarcinoma: A Propensity Score Matched Analysis of the National Cancer Database.

Factors associated with refusal of multimodality therapy in patients with localized esophageal adenocarcinoma (EA) remain unknown. We hypothesized that sociodemographic disparities affect decision to pursue optimal trimodally therapy for patients with EA. NCDB for esophageal cancer (2004-2017) was utilized. Included were patients diagnosed with cT3-T4 cN0 or cTany N1-3 EA of the mid-lower esophagus. Annual institutional esophagectomy volumes were categorized as low (<20/year) and high (≥20/year). Conditional logistic regression was used to identify predictors of refusal of offered treatment. Kaplan Meier method was used to compare survival. 13091 patients met selection criteria, mean age was 62.4 ± 9.6 years and 11581 (88.5%) were males. 633 (4.8%) patients refused at least one component of recommended treatment (chemotherapy, radiation, and esophagectomy), most commonly refusal of surgery (N = 554, 4.2%). On multivariable analysis, factors predictive of treatment refusal included older age, female gender, black race, no insurance, low income (below poverty), mid-esophageal tumors, and treatment at low-volume centers. Patients who were recommended treatment but refused had significantly worse survival than those who adhered to treatment (median 23.1 ± 1.1 vs. 32.1 ± 1.2months; P < .001). In this study, sociodemographic disparities and center volume were among factors predictive of therapy refusal in patients with localized esophageal adenocarcinoma. While understanding potential reasons for treatment refusal is critical, this data suggests that socioeconomic variables may drive patient decisions.

Alpha radionuclide-chelated radioimmunotherapy promoters enable local radiotherapy/chemodynamic therapy to discourage cancer progression

BackgroundAstatine-211 is an α-emitter with high-energy α-ray and high cytotoxicity for cancer cells. However, the targeted alpha therapy (TAT) also suffers from insufficient systematic immune activation, resulting in tumor metastasis and relapse. Combined immune checkpoint blockade (ICB) with chemodynamic therapy (CDT) could boost antitumor immunity, which may magnify the immune responses of TAT. This study aims to discourage tumor metastasis and relapse by tri-model TAT-CDT-ICB strategy.MethodsWe successfully designed Mn-based radioimmunotherapy promoters (211At-ATE-MnO2-BSA), which are consisting of 211At, MnO2 and bovine serum albumin (BSA). The efficacy of 211At-ATE-MnO2-BSA was studied as monotherapy or in combination with anti-PD-L1 in both metastatic and relapse models. The immune effects of radioimmunotherapy promoters on cytotoxic T lymphocytes and dendritic cells (DCs) were analyzed by flow cytometry. Enzyme-linked immunosorbent assay and immunofluorescence were used to explore the underlying mechanism.ResultsSuch radioimmunotherapy promoters could not only enhance the therapeutic outcomes of TAT and CDT, but also induce robust anti-cancer immune activity by activating dendritic cells. More intriguingly, 211At-ATE-MnO2-BSA could effectively suppress the growths of primary tumors and distant tumors when combined with immune checkpoint inhibitors.ConclusionsThe tri-model TAT-CDT-ICB strategy provides a long-term immunological memory, which can protect against tumor rechallenge after eliminating original tumors. Therefore, this work presents a novel approach for TAT-CDT-ICB tri-modal cancer therapy with repressed metastasis and relapse in clinics.

The role of surgery for locally advanced urothelial cancers.

Extirpative surgery can play an important role in the management strategies for locally advanced urothelial carcinoma. The current review is intended to relay current information reported in the literature over the past 12 months regarding the usage of surgical resection in advanced urothelial cancers of the bladder and upper tracts, document operative outcomes, and oncologic efficacy. Multimodal therapy is key to long-term overall survival for advanced urothelial carcinoma. Radical cystectomy with bilateral pelvic lymph node dissection can be performed after an observable response to chemotherapy or immunotherapy for cT4 or cN2 and higher node-positive disease of the bladder. Moreover, radical cystectomy after trimodal therapy similarly yields durable local response. For upper tract disease, nephroureterectomy with regional lymphadenectomy is the primary surgical modality used often in conjunction with perioperative cisplatin-based chemotherapy. Surgical resection as a monotherapy is not curative in patients with locally advanced urothelial carcinoma. However, its use in combination with systemic agents can potentiate durable long-term survival in a subset of patients. Future studies investigating patient-reported outcomes among those receiving consolidative surgery for locally advanced disease are warranted to guide clinical recommendations.

Multimodality Therapy in Patients With Primary Pericardial Mesothelioma

IntroductionPrimary pericardial mesothelioma (PPM) has no accepted standard-of-care treatment options with management and outcomes often extrapolated from diffuse pleural mesothelioma. Disease-specific research is needed to better define PPM. We report our institutional experience with PPM highlighting the potential role for multimodality therapy. MethodsPatients with PPM diagnosed by a multidisciplinary team of medical oncologists, thoracic surgeons, thoracic pathologists, and radiologists between January 2011 and January 2022 were followed to February 2022. Clinicopathologic features and treatment outcomes were annotated. Overall survival (OS) was defined from the date of pathologic diagnosis. ResultsThe median age at diagnosis of the 12 patients identified with having PPM was 51 (range: 21–71) years old. Most patients were of female sex (n = 8; 67%), 75% of the samples were epithelioid (n = 9), and 25% were nonepithelioid (two sarcomatoid and one biphasic). Most cases (92%, 11 of 12) had expression of at least two mesothelial markers on immunohistochemistry. The median OS of the cohort was 25.9 months. Five patients had an OS greater than 12 months; four of whom received pericardial radiation. Three of the patients who received radiation did so as part of a trimodality approach (surgical resection, adjuvant chemotherapy, and radiation); the OS for patients who received trimodality therapy was 70.3 months versus 8.2 months for those who did not. ConclusionsPPM represents a distinct disease with no universally accepted treatment options. Our findings suggest that trimodality therapy may improve outcomes in selected patients with PPM.

Checklist for Improving Patient Communication on Bladder Preservation Options: The Patient Advocate Perspective

Trimodal therapy (TMT) – maximal transurethral resection of bladder tumour followed by chemotherapy and radiation – is an effective treatment for some patients diagnosed with muscle-invasive bladder cancer. Yet eligible patients are not always offered this option or are unclear that this option is (or was) appropriate, desirable and available to them. Communication challenges are a critical barrier to delivering the high-quality care and shared decision-making that bladder cancer patients seek. Leveraging patient and clinician feedback, a checklist was created and is proposed that proactively addresses patients' concerns and questions and ensures that patients are well-informed about TMT. By using the checklist, members of multidisciplinary bladder cancer medical teams can ensure that patients are well-informed about TMT and are confident that TMT has been appropriately and jointly explored as a treatment option. The checklist can reduce communication challenges and frustrations and ensure that, through shared decision-making, patients have chosen their most appropriate treatment.

Patterns of care amongst older adults diagnosed with locally advanced esophageal cancer: A cohort study

IntroductionSince the early 2010s, neoadjuvant chemoradiation followed by esophagectomy (trimodal therapy) has been a recommended treatment for patients diagnosed with locally advanced esophageal cancer. However, it may also add treatment-related toxicity, particularly for older adults with significant comorbidity and frailty burdens. We examined contemporary patterns of care in older adults, which have not been well characterized. Materials and MethodsWe used the Surveillance Epidemiology and End Results-Medicare database to identify a cohort of US adults aged 66 years and older diagnosed with incident locally advanced esophageal cancer between 2004 and 2017. Calendar year age-standardized percentages of treatment receipt were calculated. Joinpoint regression was used to detect temporal trends in treatment receipt. Descriptive associations between patient factors and treatment were assessed. Trend analyses quantified how the percentage of trimodal and definitive chemoradiation (no surgery) patients receiving cisplatin-based, carboplatin-based, and other chemotherapy regimens evolved over time. ResultsIn total, 4332 adults aged ≥66 years with locally advanced esophageal cancer were included. The age-standardized percentage of patients receiving trimodal therapy increased from 16.7% in 2004 to 26.1% in 2017 (annual percent change = 3.5%; 95% confidence interval [CI], 0.7%–6.4%) in adenocarcinomas and from 7.3% in 2004 to 9.1% in 2017 (annual percent change = 0.4%; 95% CI, −4.1%–5.1%) in squamous cell carcinomas. By 2017, definitive chemoradiation became the most frequently used treatment modality for adenocarcinomas (49.8%; 95% CI, 43.5–56.0) and squamous cell carcinomas (59.5%; 95% CI, 50.8–68.2). Patients with higher comorbidity and frailty burdens were less likely to be treated with trimodal therapy. Amongst patients receiving chemoradiation as part of their treatment, a large and swift channeling away from cisplatin and towards carboplatin-based regimens was observed. DiscussionIn practice, definitive chemoradiation is the most commonly received treatment by older adults with locally advanced esophageal cancer. Four out of five older adults do not receive trimodal therapy, some of whom are potentially undertreated.

Time to Surgery for Patients with Esophageal Cancer Undergoing Trimodal Therapy in Ontario: A Population-Based Cross-Sectional Study.

Patients with resectable esophageal cancer are recommended to undergo chemoradiotherapy before esophagectomy. A longer time to surgery (TTS) and/or time to consultation (TTC) may be associated with inferior cancer-related outcomes and heightened anxiety. Thoracic cancer surgery centers (TCSCs) oversee esophageal cancer management, but differences in TTC/TTS between centers have not yet been examined. This Ontario population-level study used linked administrative healthcare databases to investigate patients with esophageal cancer between 2013–2018, who underwent neoadjuvant chemoradiotherapy and then surgery. TTC and TTS were time from diagnosis to the first surgical consultation and then to surgery, respectively. Patients were assigned a TCSC based on the location of the surgery. Patient, disease, and diagnosing physician characteristics were investigated. Quantile regression was used to model TTS/TTC at the 50th and 90th percentiles and identify associated factors. The median TTS and TTC were 130 and 29 days, respectively. The adjusted differences between the TCSCs with the longest and shortest median TTS and TTC were 32 and 18 days, respectively. Increasing age was associated with a 16-day longer median TTS. Increasing material deprivation was associated with a 6-day longer median TTC. Significant geographic variability exists in TTS and TTC. Therefore, the investigation of TCSC characteristics is warranted. Shortening wait times may reduce patient anxiety and improve the control of esophageal cancer.

Guideline on trimodal therapy of bladder cancer (Nevskiy consensus 2021)

The aim of this work was to clarify and extend the existing clinical guidelines on organ-sparing treatment of muscleinvasive bladder cancer. The standard protocol of radical conservative treatment for muscle-invasive bladder cancer includes transurethral resection of the bladder, external beam radiotherapy with simultaneous chemotherapy (radiosensitization), which is usually referred to as trimodal therapy. The implementation of trimodal therapy into routine practice in Russia is limited due to the lack of distinct criteria for each of the stages. The involvement of surgeons, radiation oncologists, and chemotherapists, on the one hand, provides the required multidisciplinary approach to cancer treatment; on the other hand, it might impede the entire algorithm. To address this problem, specialists from the Department of Radiology (project moderators), Department of Cancer Urology, and Department of Chemotherapy of N.N. Petrov National Medical Research Center of Oncology under the auspices of Saint Petersburg Oncological Research Society formed a group of experts, including radiation oncologists, urologists, and chemotherapists from federal and local cancer (educational) institutions of Saint Petersburg who had an experience of treating muscle-invasive bladder cancer. The guideline was developed with the consideration of available guidelines published by leading professional associations of radiotherapy and oncology (urological), research articles, and own experience.

Prognostic Significance of Pseudotime from Texture Parameters of FDG PET/CT in Locally Advanced Non-Small-Cell Lung Cancer with Tri-Modality Therapy.

Texture analysis provides image parameters from F-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT). Although some parameters are associated with tumor biology and clinical features, the types and implications of these parameters are complicated. We applied pseudotime analysis, which has recently been used to estimate changes in individual sample characteristics, to texture parameters from FDG PET/CT images of locally advanced non-small-cell lung cancer (NSCLC) patients undergoing neoadjuvant concurrent chemoradiation therapy (CCRT) followed by surgery. Our subjects were 303 NSCLC patients who underwent pretherapeutic FDG PET/CT and tri-modality therapy. Texture parameters of the primary tumor were calculated from FDG PET/CT images acquired before neoadjuvant CCRT. Pseudotime analysis was performed using the PhenoPath tool. Clinicopathologic features including survival data were collected and survival analysis was performed to compare the prognostic significances of pseudotime parameters with those of conventional PET parameters. Pseudotime was successfully estimated from texture parameters. Normalized co-occurrence homogeneity, normalized co-occurrence inverse difference moment, and black-white symmetry showed positive correlations with pseudotime, short run emphasis, normalized co-occurrence dissimilarity, and short zone emphasis negative correlation. The maximum standardized uptake value (SUV) and mean SUV were not associated with overall survival. Pseudotime, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) showed significant associations with overall survival. In contrast to MTV and TLG, pseudotime was an independent prognostic factor for overall survival. Various metabolic texture parameters can be integrated into a single parameter using pseudotime analysis. Pseudotime of the primary tumor, estimated from FDG PET/CT images, better predicts overall survival in locally advanced NSCLC patients treated with tri-modality therapy than conventional PET parameters.

Trimodal Therapy in Esophageal Squamous Cell Carcinoma: Role of Adjuvant Therapy Following Neoadjuvant Chemoradiation and Surgery.

Simple SummaryIn this work, we aimed to explore the effectiveness of adjuvant therapy after trimodal therapy (neoadjuvant chemoradiotherapy and esophagectomy) in patients with thoracic esophageal squamous cell carcinoma (ESCC). Overall survival (OS) and disease-free survival (DFS) were both compared for adjuvant and non-adjuvant groups. Propensity score matching was used to eliminate the confounding factors between the two groups. Meanwhile, subgroup analysis based on a neoadjuvant-treated node stage (ypN) was performed to precisely stratify the patients and to guide the clinical decision-making at the point of care. As of now, there is no guideline or recommendation on the treatment of ESCC patients with adjuvant therapy after neoadjuvant chemoradiotherapy followed by surgery. The results of our study indicate that adjuvant therapy after trimodal therapy could shorten OS and DFS in patients with ESCC. Meanwhile, adjuvant therapy is an independently unfavorably prognostic factor for DFS. Therefore, adjuvant therapy is not recommended for ESCC patients after trimodal therapy, especially patients without nodal metastases after neoadjuvant therapy. To our knowledge, this is the first retrospective study using subgroup analysis to examine the effect of adjuvant therapy in ESCC patients after trimodal therapy by comparing overall survival and disease-free survival. The results of our study add useful evidence to recent guidelines.Background: The aim of this study was to determine the role of adjuvant therapy after neoadjuvant chemoradiotherapy and esophagectomy for esophageal squamous cell carcinoma (ESCC). Methods: The study retrospectively reviewed 447 ESCC patients who underwent neoadjuvant chemoradiotherapy and esophagectomy. Patients were divided into an adjuvant therapy group and no adjuvant therapy group. Propensity score matching was used to adjust the confounding factors. Results: 447 patients with clinical positive lymph nodes and no distant metastasis treated with neoadjuvant chemoradiotherapy and esophagectomy were eligible for analysis. After propensity score matching, there were 120 patients remaining in each group. Patients receiving adjuvant therapy had a significantly shorter post-resection overall survival (OS) and disease-free survival (DFS) when compared to patients not receiving adjuvant therapy (log-rank, OS: p = 0.046, DFS: p < 0.001). Receiving adjuvant therapy is not an independently prognostic factor for OS (hazard ratio (HR): 1.270, HR: 0.846–1.906, p = 0.249) but a significantly unfavorable independent prognostic factor for DFS (HR: 2.061, HR: 1.436–2.958, p < 0.001). Conclusions: The results of our study indicate that adjuvant therapy after neoadjuvant chemoradiotherapy and surgery could reduce the OS and DFS in patients with ESCC. Therefore, adjuvant therapy is not recommended for ESCC patients after neoadjuvant chemoradiotherapy and esophagectomy, especially patients without nodal metastases after neoadjuvant therapy.

The Rate of Prostatic Involvement in Men Treated With Radical Cystectomy for Muscle Invasive Bladder Cancer

PurposeRadical cystoprostatectomy (RC) is one standard treatment for muscle-invasive bladder cancer (MIBC) in male patients. Another therapeutic option is trimodal therapy. Including the prostate in the trimodal therapy radiation therapy volume is based on MIBC surgical series showing prostatic stromal (PS) involvement. Our aim was to establish the rate of pathologic PS involvement by preoperative T stage in men treated with RC for MIBC. Methods and MaterialsWe conducted a retrospective review of men with MIBC treated with RC between 2006 and 2019. Electronic medical records were reviewed, and preoperative clinical staging data were collected. χ2 test was done to test for a statistically significant difference in the rate of prostatic involvement between clinical tumor (cT) stages. Preoperatively identified carcinoma in situ, lymph node involvement, tumor location, and urethral involvement were also analyzed to see if they conferred a higher risk of PS involvement. Multivariate analysis using multiple logistic regression was performed. ResultsWe identified 283 men with bladder cancer treated with RC. Patients with non-MIBC or incomplete medical data were excluded (n = 72). We analyzed 211 patients, and 46 (22%) had pathologic PS involvement. PS involvement by preoperative T stage was cT2 = 18%, cT3 = 23%, and cT4 = 48%. Twenty-nine (12%) patients had clinical lymph node involvement, of whom 19 (76%) had PS involvement. Thirty-four (16%) had urethral involvement, of whom 17 (50%) had PS involvement. Sixteen percent and 17% of percent of clinical T2 and T3 patients had bladder neck/trigone tumors, of whom 57% and 50% had prostatic involvement. Clinical T2 and T3 were not statistically different with regards to PS involvement (P = .385). Preoperative urethral involvement, lymph node involvement, cT4, and bladder neck/trigone location were statistically significant predictors of pathologic PS involvement (all P < .05). On multivariate analysis, only clinical urethral involvement was significant (P < .0001). ConclusionsThe high rate of pathologic PS involvement seen in cT2 patients and the lack of ability of cT stage to predict PS involvement support routinely treating the prostate in trimodal therapy. Patients with preoperatively identified bladder neck/trigone tumors, urethral involvement, positive lymph nodes, or prostatic involvement are a subset at even higher risk of having pathologic PS involvement.

Management of surgically inoperable muscle-invasive bladder cancer in a resource constraint setting at a tertiary care center by bladder preservation protocol: Case series.

Urinary bladder cancer is a major cause of morbidity and mortality worldwide. As per the data from the US cancer registry, it was diagnosed in nearly 71,000 patients and led to 14000 deaths in 2013. The Indian data in this regard are lacking with few case reports and epidemiological data only. The paucity of treatment data in this regard led us to undertake this prospective study at our radiation oncology canter. Carcinoma urinary bladder is a heterogeneous disease with variable natural history. Male preponderance and association with cigarette smoking appears to be the foremost in natural history of the disease. Our data analyzed the management of muscle-invasive medically and surgically inoperable carcinoma urinary bladder in a resource constraint setting at a tertiary care center by bladder preservation protocol (BPP). This prospective study was aimed to evaluate the treatment outcome in surgically inoperable muscle-invasive carcinoma urinary bladder in a resource constraint setting at a tertiary care center by BPP. All patients were treated with telecobalt 60 machine up to a dose of 60-66 Gy along with concurrent chemotherapy. Interim assessment was done at 40 Gy. A total of nine patients were taken up for treatment with BPP. All patients were evaluated with standard evaluation protocol. All patients were followed up till any event occurred and till 6 years. Out of nine patients treated, six patients are still alive without any progression of disease and are disease free with standard evaluation on follow-up. Two patients died during the 1st year of follow-up. One patient progressed with lung and abdominal metastases 5 months after the completion of treatment and one patient was lost to follow-up. BPP using trimodality therapy is a suitable alternative to radical cystectomy in medically and surgically inoperable carcinoma urinary bladder. These patients should be highly compliant for regular follow-up, and acute and long-term toxicity should be evaluated in detail at each visit. BPP gives a ray of hope in such settings and should be done with caution. In our study, we treated all these patients in our resource constraint settings with good results and high survival rates. Our integrated team of radiation oncologists, medical oncologists, and urologists closely followed up these patients in order to optimize outcomes.

Lymphedema in Inflammatory Breast Cancer Patients Following Trimodal Treatment.

Breast cancer-related lymphedema (BCRL) is a debilitating sequela of breast cancer treatment and is becoming a greater concern in light of improved long-term survival. Inflammatory breast cancer (IBC) is a rare and aggressive malignancy for which systemic therapy, surgery, and radiotherapy remain the standard of care, thereby making IBC patients highly susceptible to developing BCRL. This study evaluated BCRL in IBC following trimodal therapy. IBC patients treated from 2016 to 2019 were identified from an institutional database. Patients were excluded if they presented with recurrent disease, underwent bilateral axillary surgery, did not complete trimodal therapy, or were lost to follow-up. Demographic, clinicopathologic factors, oncologic outcomes, and perometer measurements were recorded. BCRL was defined by clinician diagnosis and/or objective perometer measurements when available. Time to development of BCRL and treatment received were captured. Eighty-three patients were included. Median follow-up was 33 months. The incidence of BCRL was 50.6% (n = 42). Mean time to BCRL from surgery was 13 (range 2-24) months. Demographic and clinicopathologic features were similar between patients with and without BCRL with exception of higher proportion receiving delayed reconstruction in the BCRL group (38.1% vs. 14.6%, p = 0.03). Forty patients (95.2%) underwent BCRL treatment, which included physical therapy (n = 39), compression (n = 38), therapeutic lymphovenous bypass (n = 13), and/or vascularized lymph node transfer (n = 12). IBC patients are at high-risk for BCRL after treatment, impacting 51% of patients in this cohort. Strategies to reduce or prevent BCRL and improve real-time diagnosis should be implemented to better direct early management in this patient population.

Long-term Oncologic Outcomes in Patients with Inflammatory Breast Cancer with Supraclavicular Nodal Involvement.

Inflammatory breast cancer (IBC) is a rare and aggressive subtype of breast cancer characterized by rapid progression and early metastasis, often with advanced nodal locations, including the supraclavicular (SCV) nodal basin. Previously considered M1 disease, ipsilateral clinical supraclavicular node involvement (N3c) disease is now considered locally advanced disease and warrants treatment with intent to cure. The objective of this study was to evaluate the long-term outcomes of patients with IBC and N3c disease. This study was conducted using a prospectively collected database of all patients with IBC treated at a dedicated cancer center from 2007 to 2019. Surgical patients with SCV nodal involvement and complete follow-up were identified. Our primary outcome was 5-year overall survival (OS). Multivariate Cox proportional hazards models were used to determine predictors for survival. Event-free survival (EFS) and OS were calculated using the Kaplan-Meier method. There were 70 patients who met inclusion criteria. All patients underwent comprehensive trimodality therapy. The majority of patients had complete (66.2%) radiologic response in the SCV nodal basins following neoadjuvant therapy. Six patients (8.6%) had a locoregional recurrence, with two (2.9%) occurring in the supraclavicular fossa. The 5-year OS was 60.2% [95% confidence interval (CI) 47.7-72.7%]. Increasing age (hazard ratio 2.7; p = 0.03) and triple-negative subtype (hazard ratio 4.9; p = 0.03) were associated with poor OS. The 5-year EFS was 56.1% (95% CI 40.9-68.8%). The presence of more than ten positive axillary nodes on final surgical pathology (hazard ratio 5.5; p = 0.01) predicted poor EFS. With comprehensive trimodality therapy and multidisciplinary team approach, patients with IBC with supraclavicular nodal involvement experience excellent locoregional control and favorable survival.

Circulating tumor cells detected in follow-up predict survival outcomes in tri-modality management of advanced non-metastatic esophageal cancer: a secondary analysis of the QUINTETT randomized trial

BackgroundOur aim was to establish if presence of circulating tumor cells (CTCs) predicted worse outcome in patients with non-metastatic esophageal cancer undergoing tri-modality therapy.MethodsWe prospectively collected CTC data from patients with operable non-metastatic esophageal cancer from April 2009 to November 2016 enrolled in our QUINTETT esophageal cancer randomized trial (NCT00907543). Patients were randomized to receive either neoadjuvant cisplatin and 5-fluorouracil (5-FU) plus radiotherapy followed by surgical resection (Neoadjuvant) or adjuvant cisplatin, 5-FU, and epirubicin chemotherapy with concurrent extended volume radiotherapy following surgical resection (Adjuvant). CTCs were identified with the CellSearch® system before the initiation of any treatment (surgery or chemoradiotherapy) as well as at 6-, 12-, and 24-months post-treatment. The threshold for CTC positivity was one and the findings were correlated with patient prognosis.ResultsCTC data were available for 74 of 96 patients and identified in 27 patients (36.5%) at a median follow-up of 13.1months (interquartile range:6.8-24.1 months). Detection of CTCs at any follow-up visit was significantly predictive of worse disease-free survival (DFS;hazard ratio [HR]: 2.44; 95% confidence interval [CI]: 1.41-4.24; p=0.002), regional control (HR: 6.18; 95% CI: 1.18-32.35; p=0.031), distant control (HR: 2.93; 95% CI: 1.52-5.65;p=0.001) and overall survival (OS;HR: 2.02; 95% CI: 1.16-3.51; p=0.013). After adjusting for receiving neoadjuvant vs. adjuvant chemoradiotherapy, the presence of CTCs at any follow-up visit remained significantly predictive of worse OS ([HR]:2.02;95% [Cl]:1.16-3.51; p=0.013) and DFS (HR: 2.49;95% Cl: 1.43-4.33; p=0.001). Similarly, any observed increase in CTCs was significantly predictive of worse OS (HR: 3.14; 95% CI: 1.56-6.34; p=0.001) and DFS (HR: 3.34; 95% CI: 1.67-6.69; p<0.001).ConclusionThe presence of CTCs in patients during follow-up after tri-modality therapy was associated with significantly poorer DFS and OS regardless of timing of chemoradiotherapy.

Neoadjuvant Therapy in the Post–German Rectal Trial Era: Making Sense in the Absence of Consensus

Trimodality therapy per the German Rectal Trial has led to excellent locoregional outcomes for locally advanced rectal cancer. Recent efforts have shifted toward improving distant control and health-related quality of life in this disease. To this end, total neoadjuvant therapy has become an increasingly used approach in which most, if not all, chemotherapy is delivered before surgery to improve compliance and to address micrometastases early. To avoid surgical morbidity, a “watch-and-wait” approach, in which total mesorectal excision is deferred, has also been studied for patients who achieve a clinical complete response after chemoradiation. These 2 concurrent treatment trends have raised many points of uncertainty in what used to be a relatively straightforward neoadjuvant treatment paradigm. We discuss here our approach to neoadjuvant therapy for locally advanced rectal cancer, based on the data we currently have and through shared decision-making with patients to help them select the treatment that best aligns with their preferences and values.

The prognostic value of urinary cytology after trimodal therapy (TMT) for muscle-invasive bladder cancer.

Urine cytology and cystoscopy are routinely employed during follow-up of patients after trimodal therapy (TMT) for muscle-invasive bladder cancer (MIBC). The significance of positive or equivocal cytology without visible disease recurrence on cystoscopy during follow-up is unknown, and studies informing outcomes in this scenario are lacking. This study aims to investigate the temporal trends of positive/equivocal cytology in the absence of visible disease recurrence and the association with bladder cancer recurrence and survival outcomes. One hundred and twenty-nine patients with available post-TMT cytology data and negative cystoscopy from a single academic institution between 2002 and 2017 with a median follow-up of 3.4 (range 0.1-14.2) years were analyzed. Cytology results, first post-TMT cytology positive/equivocal (CP) and negative (CN), were evaluated for association with disease recurrence and survival. Kaplan. Meier and competing risks methods were used to assess time-to-negative cytology in CP patients with ≥2 interval post-TMT cytology results (n = 33), time-to-recurrence, and disease-specific mortality (DSM) stratified by first post-TMT cytology result. At first follow-up (6-8 weeks post-TMT completion), CP was observed in 41 (32%) and CN in 88 (68%) of patients. With further follow-up of CP patients with ≥2 interval post-TMT cytology results, the probability of developing negative cytology was 57% (95% CI 42, 77) at 6 months post-TMT, and the median time-to-negative cytology was 3.2 months (95% CI 2.99, 5.80). The median time-to-recurrence was reduced in CP patients compared to CN (24.3 vs. 78.1 months, p = 0.1), corresponding with an apparent increase in the cumulative incidence of recurrence rate at 3 years in the CP vs. CN group (62% vs. 42%, p = 0.1). No significant difference was observed in the 3-year DSM rates. On univariable analysis, the hazards of recurrence and DSM for patients with CP were 1.5 (95% CI 0.9, 2.5, p = 0.1) and 2.1 (95% CI 0.9, 4.7, p = 0.07) respectively. This is the first study to investigate the significance of a positive/equivocal cytology without visible disease following TMT for MIBC. Positive cytology is common and does not preclude subsequent negative cytology supporting a watchful waiting approach rather than proceeding immediately to biopsy. However, cytology that remains positive at subsequent follow-up may be associated with adverse recurrence and survival outcomes.