Machine learning-based response assessment in patients with rectal cancer after neoadjuvant chemoradiotherapy: radiomics analysis for assessing tumor regression grade using T2-weighted magnetic resonance images.

PURPOSE: This study aimed to assess tumor regression grade (TRG) in patients with rectal cancer after neoadjuvant chemoradiotherapy (NCRT) through a machine learning-based radiomics analysis using baseline T2-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: In total, 148 patients with locally advanced rectal cancer(T2-4 or N+) who underwent MR imaging at baseline and after chemoradiotherapy between January 2010 and May 2021 were included. A region of interest for each tumor mass was drawn by a radiologist on oblique axial T2-weighted images, and main features were selected using principal component analysis after dimension reduction among 116 radiomics and three clinical features. Among eight learning models that were used for prediction model development, the model showing best performance was selected. Treatment responses were classified as either good or poor based on the MR-assessed TRG (mrTRG) and pathologic TRG (pTRG). The model performance was assessed using the area under the receiver operating curve (AUROC) to classify the response group. RESULTS: Approximately 49% of the patients were in the good response (GR) group based on mrTRG (73/148) and 26.9% based on pTRG (28/104). The AUCs of clinical data, radiomics models, and combined radiomics with clinical data model for predicting mrTRG were 0.80 (95% confidence interval [CI] 0.73, 0.87), 0.74 (95% CI 0.66, 0.81), and 0.75(95% CI 0.68, 0.82), and those for predicting pTRG was 0.62 (95% CI 0.52, 0.71), 0.74 (95% CI 0.65, 0.82), and 0.79 (95% CI 0.71, 0.87). CONCLUSION: Radiomics combined with clinical data model using baseline T2-weighted MR images demonstrated feasible diagnostic performance in predicting both MR-assessed and pathologic treatment response in patients with rectal cancer after NCRT.

The Addition of Chemoradiation to Adjuvant Chemotherapy is Associated With Improved Survival Following Upfront Surgical Resection for Pancreatic Cancer With Nodal Metastases.

BACKGROUND: It is unclear whether the addition of chemoradiation (CRT) to adjuvant chemotherapy (CT) following upfront resection of pancreatic ductal adenocarcinoma (PDAC) provides any benefit. While some studies have suggested a benefit to combined modality therapy (CMT) (adjuvant CT plus CRT), it is not clear if this benefit was related to increased CT usage in patients who received CMT. We sought to clarify the use of CMT in patients who underwent upfront resection of PDAC. METHODS: Patients with non-metastatic PDAC were retrospectively identified from the linked SEER-Medicare database. Those who underwent upfront resection were identified and divided into two cohorts - patients who received adjuvant CT and patients who received adjuvant CMT. Cohorts were compared. Univariate analysis described patient characteristics. Kaplan-Meier and multivariable Cox proportional hazards modeling were used to estimate overall survival (OS). RESULTS: 3555 patients were identified; 856 (24%) received CT and 573 (16%) received CMT. The median number of CT doses was 11 for both groups. Patients who received CMT were younger, diagnosed in the earlier time frame, and had fewer comorbidities. The median OS was 21 months and 18 months for those treated with CMT and CT (P < .0001), respectively, but when stratified by nodal status, the association with improved OS in the CMT cohort was only observed in node-positive patients. On multivariable analysis, receipt of CMT and removal of >15 lymph nodes decreased the risk of death (P < .05). DISCUSSION: Receipt of CMT following upfront resection for PDAC was associated with improved survival, which was confined to node-positive patients. The role of adjuvant CMT in PDAC with nodal metastases warrants further study.

Risk assessment in the patients with uterine cervical cancer harboring intermediate risk factors after radical hysterectomy: a multicenter, retrospective analysis by the Japanese Gynecologic Oncology Group.

BACKGROUND: Adjuvant therapy is usually considered for surgically treated patients with uterine cervical cancer harboring intermediate risk (IR) factors such as large tumor diameter, stromal invasion to the outer half, and lymphovascular space invasion (LVSI). However, the indications and types of adjuvant therapy for the IR group remain controversial. This study aimed to analyze the differences in patient outcomes in the IR group to provide novel insights for tailoring adjuvant therapy. METHODS: Data from 6192 patients with cervical cancer who underwent radical hysterectomy at 116 institutions belonging to the Japanese Gynecologic Oncology Group were reviewed. RESULTS: In total, 1688 patients were classified into the IR group, of whom 37.3% did not receive adjuvant therapy. Conversely, approximately equal proportions of the remaining patients received adjuvant radiotherapy, concurrent chemoradiotherapy, and chemotherapy. Patients with all three risk factors showed worse overall survival than those with one or two risk factors. In addition to LVSI, non-squamous cell carcinoma histology, and vaginal invasion were identified as independent risk factors for both recurrence and mortality in multivariate analyses. Tumor diameter greater than 40 mm and surgical center volume were identified as independent risk factors for recurrence. Stromal invasion to the outer half and ovarian metastasis were identified as independent risk factors for mortality. CONCLUSIONS: This study revealed the significant differences in prognosis in the IR group. The indications for adjuvant therapy should be further studied, focusing on conventional risk factors and other pathological findings.

Assessment of the external validity of the National Comprehensive Cancer Network (NCCN) guidelines for pancreatic ductal adenocarcinoma in a population of older patients aged 70 years and older.

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) mainly occurs in older adults. Since randomized clinical trials (RCTs) provide the highest-quality evidence incorporated in NCCN recommendations, the underrepresentation of older patients in RCTs challenges guidelines' external validity and limits the solidity of evidence in this specific population. MATERIALS AND METHODS: The study aimed to investigate external validity of NCCN guidelines for PDCA and the impact of reference studies eligibility on overall survival (OS) in a real-world older population. We retrieved RCTs supporting NCCN recommendations for management of PDAC and identified ten topics. We matched a cohort of 707 PDAC patients aged ≥70 years from the Moffitt Cancer Center database with eligibility criteria of 96 reference RCTs to check the proportion of patients eligible for at least two RCTs. Eligibility >60% was rated full validity, 30%-60% partial validity and < 30% limited validity. We also performed log-rank test to assessed whether "eligibility" status affects OS, stratifying by age (70-74; 75-79; ≥80). RESULTS AND DISCUSSION: We found full validity for neoadjuvant (57/73 patients; 69.86%), locally advanced (28/39; 71.79%) and second line (88/110; 80%) treatment, while lowest validity was found for adjuvant chemotherapy (37/86; 43%). Eligible status was correlated with a significant OS benefit for adjuvant chemoradiation (p = 0.002) in all-comers and for first-line polychemotherapy in patients aged ≥80 (p = 0.01). Our analysis supports the limitation of guidelines' external validity in older patients, and hints at possible correlations with survival, although no definitive conclusions can be drawn at this stage. Renewing RCT design with broader eligibility criteria might help increase inclusion of older and thus strengthen the evidence.

Cervical cancer treatment in Rwanda: Resource-driven adaptations, quality indicators, and patient outcomes.

OBJECTIVE: Most cervical cancer cases and deaths occur in low- and middle-income countries, yet clinical research from these contexts is significantly underrepresented. We aimed to describe the treatment quality, resource-driven adaptations, and outcomes of cervical cancer patients in Rwanda. METHODS: A retrospective cohort study was conducted of all patients with newly diagnosed cervical cancer enrolled between April 2016 and June 2018. Data were abstracted from medical records and analyzed using descriptive statistics, Kaplan Meier methods, and Cox proportional hazards regression. RESULTS: A total of 379 patients were included; median age 54 years, 21% HIV-infected. A majority (55%) had stage III or IV disease. Thirty-four early-stage patients underwent radical hysterectomy. Of 254 patients added to a waiting list for chemoradiation, 114 ultimately received chemoradiation. Of these, 30 (26%) received upfront chemoradiation after median 126 days from diagnosis, and 83 (73%) received carboplatin/paclitaxel while waiting, with a median 56 days from diagnosis to chemotherapy and 207 days to chemoradiation. There was no survival difference between the upfront chemoradiation and prior chemotherapy subgroups. Most chemotherapy recipients (77%) reported improvement in symptoms. Three-year event-free survival was 90% with radical hysterectomy (95% CI 72-97%), 66% with chemoradiation (95% CI 55-75%), and 12% with chemotherapy only (95% CI 6-20%). CONCLUSIONS: Multi-modality treatment of cervical cancer is effective in low resource settings through coordinated care and pragmatic approaches. Our data support a role for temporizing chemotherapy if delays to chemoradiation are anticipated. Sustainable access to gynecologic oncology surgery and expanded access to radiotherapy are urgently needed.

Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx.

PURPOSE: De-escalated treatment for human papillomavirus (HPV)+ oropharynx squamous cell carcinoma (OPSCC) has shown promising initial results. Health-care policy is increasingly focusing on high-value care. This analysis compares the cost of care for HPV+ OPSCC treated with definitive chemoradiation (CRT), surgery and adjuvant radiation (RT), and surgery and de-escalated CRT on MC1273. METHODS AND MATERIALS: MC1273 is a prospective, phase 2 study evaluating adjuvant CRT to 30 to 36 Gy plus docetaxel for HPV+ OPSCC after surgery for high-risk patients. Matched standard-of-care control groups were retrospectively identified for patients treated with definitive CRT or adjuvant RT. Standardized costs were evaluated before radiation, during treatment (during RT), and at short-term (6 month) and long-term (7-24 month) follow-up periods. RESULTS: A total of 56 definitive CRT, 101 adjuvant RT, and 66 MC1273 patients were included. The CRT arm had more T3-4 disease (63% vs 17-21%) and higher N2c-N3 disease (52% vs 20-24%) vs both other groups. The total treatment costs in the CRT, adjuvant RT, and MC1273 groups were $47,763 (standard deviation [SD], $19,060], $57,845 (SD, $17,480), and $46,007 (SD, $9019), respectively, and the chemotherapy and/or RT costs were $39,936 (SD, $18,480), $26,603 (SD, $12,542), and $17,864 (SD, $3288), respectively. The per-patient, per-month, average short-term follow-up costs were $3860 (SD, $10,525), $1072 (SD, $996), and $972 (SD, $833), respectively, and the long-term costs were $978 (SD, $2294), $485 (SD, $1156), and $653 (SD, $1107), respectively. After adjustment for age, T-stage, and N-stage, treatment costs remained lower for CRT and MC1273 versus adjuvant RT ($45,450 and $47,114 vs $58,590, respectively; P < .001), whereas the total per-patient, per-month follow-up costs were lower in the MC1273 study group and adjuvant RT versus CRT ($853 and $866 vs $2030, respectively; P = .03). CONCLUSIONS: MC1273 resulted in 10% and 20% reductions in global costs compared with standard-of-care adjuvant RT and definitive CRT treatments. Substantial cost savings may be an added benefit to the already noted low toxicity and maintained quality of life of treatment per MC1273.

"A prospective study of assessment of neurocognitive function in illiterate patients with gliomas treated with chemoradiation": Assessment of neurocognitive function in gliomas.

OBJECTIVE: Neurocognitive functioning (NCF) is an important component of quality of life (QoL) in glioma patients. The neurocognitive toxicity from irradiation of brain tumours may be related to damage to neural progenitor cells (NPC). The aim of our study was to assess the NCF in illiterate glioma patients. METHODS: This was a prospective study done in glioma patients admitted for adjuvant treatment. Illiterate and semiliterate post op glioma patients with ECOG PS ≤ 3 were included. Neurocognitive assessment was done using Addenbrooke's Cognitive Examination (ACE-III) questionnaire prior to the start of RT and at 6month and 12 month follow up. The scores were correlated to the doses to sub ventricular zone (SVZ) and sub granular zone (SGZ) regions. RESULTS: 20 patients were recruited.16 patients were illiterate and four patients were semiliterate. Median of the mean dose to the SVZ I/L (ipsilateral) was 48.5 Gy and SGZ I/L was 39.5 Gy. In patients who received ≤49 Gy mean dose to SVZ I/L, there was statistically significant improvement in memory, fluency, language and total ACE scores at six months. In patients with SGZ I/L mean dose ≤40 Gy, there was improvement in memory, language, and total ACE score at six months. Similar trend continued at 12 months follow up. CONCLUSIONS: NCF assessment by ACE III questionnaire is a useful tool even in illiterate patients. Lower RT doses to the ipsilateral SVZ and SGZ showed significant improvement in total ACE scores at 6 months and improvement in specific domains at 6 and 12 months.

The Impact of Socioeconomic Deprivation on Clinical Outcomes for Pancreatic Adenocarcinoma at a High-volume Cancer Center: A Retrospective Cohort Analysis.

OBJECTIVE: To assess the impact of a granular measure of SED on pancreatic surgical and cancer-related outcomes at a high-volume cancer center that employs a standardized clinic pathway. SUMMARY OF BACKGROUND DATA: Prior research has shown that low socioeconomic status leads to less treatment and worse outcomes for PDAC. However, these studies employed inconsistent definitions and categorizations of socioeconomic status, aggregated individual socioeconomic data using large geographic areas, and lacked detailed clinicopathologic variables. METHODS: We conducted a retrospective cohort study of 1552 PDAC patients between 2008 and 2015. Patients were stratified using the area deprivation index, a validated dataset that ranks census block groups based on SED. Multivariable models were used in the curative surgery cohort to predict the impact of SED on (1) grade 3/4 Clavien-Dindo complications, (2) initiation of adjuvant therapy, (3) completion of adjuvant therapy, and (4) overall survival. RESULTS: Patients from high SED neighborhoods constituted 29.9% of the cohort. Median overall survival was 28 months. The rate of Clavien-Dindo grade 3/4 complications was 14.2% and completion of adjuvant therapy was 65.6%. There was no evidence that SED impacted surgical evaluation, receipt of curative-intent surgery, postoperative complications, receipt of adjuvant therapy or overall survival. CONCLUSIONS: Although nearly one-quarter of curative-intent surgery patients were from high SED neighborhoods, this factor was not associated with measures of treatment quality or survival. These observations suggest that treatment at a high-volume cancer center employing a standardized clinical pathway may in part address socioeconomic disparities in pancreatic cancer.

Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project.

INTRODUCTION: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. METHOD: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006-2009; II)2010-2013; III)2014-2017. Survival analyses were run for 3-year survival in timeframes I-II. RESULTS: Out of 14,391 patients,8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ±â€¯chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%,p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59-0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. CONCLUSION: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most.

Treatment and Outcomes of Women With Large Locally Advanced Breast Cancer.

Advances in breast cancer research have made breast cancer a treatable disease. However, there is a population of women who present with large, advanced, or sometimes neglected breast cancers who can prove difficult to treat. These women often require multiple modality treatment including chemotherapy, surgery, and radiation. The purpose of our study is to examine the treatment and outcomes on women with large, locally advanced breast cancers (LABCs).We identified 8 individuals who presented with LABCs requiring extensive treatment. Patients with inflammatory or metastatic cancer at the time of presentation were excluded. These patients' charts were reviewed and analyzed. Patient demographics, hormone receptor status, stage, types of treatment, presence of metastasis, survival, and presence of barriers for seeking treatment sooner were identified.The median age at presentation was 65 years old. The patients were equally African American and Caucasian. All patients presented with T4 or stage 3 tumors involving the skin and/or pectoralis muscle. Half of the patients were found to have triple-negative (estrogen receptor, progesterone receptor, Her-2/neu negative) tumors. 87% of the patients received chemotherapy; 1 refused. All 8 patients, either neoadjuvantly or adjuvantly, underwent a modified radical or radical mastectomy. Skin graft or flap coverage was necessary in half of the patients. Postmastectomy radiation was received in 87% of the patients; 1 patient refused the treatment. Half of the patients developed metastatic disease. Thirty-seven percent of the patients have since died with a median survival of 44 months. Reasons for delay in seeking care were monetary or social barriers. Many of the patients finally sought care via the emergency room due to symptoms they could no longer ignore.Women who present with LABC require complex multidisciplinary treatment consisting of chemotherapy, surgery, and radiation treatments. Many of these patients faced economic and social challenges to accessing care. Better access to care and more prompt connection to breast surgeons are required to assist this patient population.

Toxicity after adjuvant therapy for stage III uterine cancer.

OBJECTIVE: The optimal adjuvant therapy for stage III endometrial cancer is unknown. Studies have suggested that combination therapy with chemotherapy and radiation is associated with improved survival. We examined early and late-term toxicities associated with chemotherapy (CT), external beam radiotherapy (RT), or combination chemoradiotherapy for stage III uterine cancer. METHODS: The SEER-Medicare database was used to identify women age ≥ 65 years with stage III uterine cancer who received adjuvant CT, RT, or chemoradiotherapy from 2000 to 2015. The associations between therapy and early and late-term toxicities identified with billing claims, hospitalizations and emergency department visits were examined using multivariable regression models. RESULTS: A total of 2185 patients were identified including 574 (26.3%) who received CT, 636 (29.1%) who received RT, and 975 (44.6%) who received chemoradiotherapy. The proportion of patients receiving chemoradiotherapy or CT increased over time. During the first 6 and 12 months of adjuvant therapy, RT was associated with a lower risk of early-term toxicity compared to chemoradiotherapy (aRR = 0.59, 95%CI 0.49-0.70 and aRR = 0.76, 95%CI 0.67-0.86, respectively) while CT shared a similar risk of early toxicities as chemoradiotherapy. CT and RT shared a similar risk of late-term toxicities compared to chemoradiotherapy. CT and RT alone were associated with a higher hazard for overall mortality than chemoradiotherapy (aHR = 1.27, 95% CI 1.10-1.47 and aHR = 1.25, 95% CI 1.08-1.44, respectively). CONCLUSION: Chemoradiotherapy is associated with lower mortality compared to single modality therapy and has a similar risk of early and late term toxicities compared to CT, though higher risk of early toxicities compared to RT.

Objective assessment of tumor regression in post-neoadjuvant therapy resections for pancreatic ductal adenocarcinoma: comparison of multiple tumor regression grading systems.

Neoadjuvant therapy is increasingly used to control local tumor spread and micrometastasis of pancreatic ductal adenocarcinoma (PDAC). Pathology assessments of treatment effects might predict patient outcomes after surgery. However, there are conflicting reports regarding the reproducibility and prognostic performance of commonly used tumor regression grading systems, namely College of American Pathologists (CAP) and Evans' grading system. Further, the M.D. Anderson Cancer Center group (MDA) and the Japan Pancreas Society (JPS) have introduced other grading systems, while we recently proposed a new, simple grading system based on the area of residual tumor (ART). Herein, we aimed to assess and compare the reproducibility and prognostic performance of the modified ART grading system with those of the four grading systems using a multicenter cohort. The study cohort consisted of 97 patients with PDAC who had undergone post-neoadjuvant pancreatectomy at four hospitals. All patients were treated with gemcitabine and S-1 (GS)-based chemotherapies with/without radiation. Two pathologists individually evaluated tumor regression in accordance with the CAP, Evans', JPS, MDA and ART grading systems, and interobserver concordance was compared between the five systems. The ART grading system was a 5-tiered system based on a number of 40× microscopic fields equivalent to the surface area of the largest ART. Furthermore, the final grades, which were either the concordant grades of the two observers or the majority grades, including those given by the third observer, were correlated with patient outcomes in each system. The interobserver concordance (kappa value) for Evans', CAP, MDA, JPS and ART grading systems were 0.34, 0.50, 0.65, 0.33, and 0.60, respectively. Univariate analysis showed that higher ART grades were significantly associated with shorter overall survival (p = 0.001) and recurrence-free survival (p = 0.005), while the other grading systems did not show significant association with patient outcomes. The present study revealed that the ART grading system that was designed to be simple and more objective has achieved high concordance and showed a prognostic value; thus it may be most practical for assessing tumor regression in post-neoadjuvant resections for PDAC.

Brief Hospital Supervision of Exercise and Diet During Adjuvant Breast Cancer Therapy Is Not Enough to Relieve Fatigue: A Multicenter Randomized Controlled Trial.

Supervised exercise dietary programs are recommended to relieve cancer-related fatigue and weight increase induced by adjuvant treatment of early breast cancer (EBC). As this recommendation lacks a high level of evidence, we designed a multicenter randomized trial to evaluate the impact of an Adapted Physical Activity Diet (APAD) education program on fatigue. We randomized 360 women with EBC who were receiving adjuvant chemotherapy and radiotherapy to APAD or usual care at eight French cancer institutions. Data were collected at baseline, end of chemotherapy, end of radiotherapy, and 6 months post-treatment. The primary endpoint was the general cancer-related fatigue score using the MFI-20 questionnaire. Fatigue correlated with the level of precariousness, but we found no significant difference between the two groups in terms of general fatigue (p = 0.274). The APAD arm has a smaller proportion of patients with confirmed depression at the end of follow-up (p = 0.052). A transient modification in physical activity levels and dietary intake was reported in the experimental arm. However, a mixed hospital- and home-based APAD education program is not enough to improve fatigue caused by adjuvant treatment of EBC. Cancer care centers should consider integrating more proactive diet-exercise supportive care in this population, focusing on precarious patients.

Examining initial treatment and survival among men with metastatic prostate cancer: An analysis from the CaPSURE registry.

BACKGROUND: New data is emerging to guide initial treatment of patients with metastatic prostate cancer (CaP). This study utilizes the Cancer of the Prostate Strategic Urologic Research Endeavor registry to evaluate variations in survival based on initial treatment received by men with metastatic disease at diagnosis or after progression. MATERIALS AND METHODS: Cancer of the Prostate Strategic Urologic Research Endeavor is a national registry of men diagnosed with CaP and managed at 43 community, academic, and Veteran's centers. We examined socio-demographic factors, disease biology, initial and subsequent therapy received, and survival among patients who presented with de novo or recurrent metastatic disease stratified by receipt of initial local therapy vs. combined local and hormonal therapy. The outcome was prostate cancer specific mortality (PCSM). We performed Fine and Gray competing risks regression analysis to evaluate the association between timing of metastasis and PCSM, adjusted for age, initial treatment, and subsequent therapy. RESULTS: Of the 14,753 patients diagnosed with CaP from 1990 to 2016, 669 (5%) had metastatic disease. Among the examined patients, 303 (45%) had metastatic disease at diagnosis and 366 (55%) progressed to metastatic disease. Overall, 461 (69%) were ≥65 years old, 582 (87%) had Medicare, and 227 (34%) had an annual income < $30,000. Prostate-specific antigen at diagnosis was >20 ng/ml for 342 (51%) patients and biopsy Gleason grade was ≥4 + 3 for 386 (58%) patients. Among patients with metastatic disease at diagnosis, 31 (10%) received initial local therapy and 272 (90%) received initial hormonal therapy. Among patients who progressed to metastatic disease, 239 (65%) received initial local therapy and 127 (35%) received initial systemic hormonal therapy. Among patients with metastatic disease, the multivariate competing risks model, after adjusting for sociodemographics, marital status, diagnosis year, and comorbidities, revealed a significantly lower risk of PCSM among patients with de novo vs. recurrent metastatic disease (Hazard Ratio 0.66 (95% Confidence Interval 0.51, 0.85) P = 0.002). In the stratified analysis, no difference was seen for patients treated with initial hormonal vs. combined local and hormonal therapy. CONCLUSIONS: In this analysis of a nationwide cohort of men treated for CaP with all types of therapy over 25 years, we observed that among men with metastatic CaP, the risk of PCSM was lower for de novo vs. recurrent metastatic disease. Additionally, no difference was observed based on initial treatment with combined local and hormonal therapy vs. hormonal therapy alone.

Avoidance of Overtreatment of Rectal Cancer by Selective Chemoradiotherapy: Results of the Optimized Surgery and MRI-Based Multimodal Therapy Trial.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) in patients with rectal cancer carries a high risk of adverse effects. The aim of this study was to examine the selective application of nCRT based on patient risk profile, as determined by MRI, to find the optimal range between undertreatment and overtreatment. STUDY DESIGN: In this prospective multicenter observational study, nCRT before total mesorectal excision (TME) was indicated in high-risk patients with involved or threatened mesorectal fascia (≤1 mm), or cT4 or cT3 carcinomas of the lower rectal third. All other patients received primary surgery. RESULTS: Of the 1,093 patients, 878 (80.3%) were treated according to the protocol, 526 patients (59.9%) underwent primary surgery, and 352 patients (40.1%) underwent nCRT followed by surgery. The 3-year locoregional recurrence (LR) rate was 3.1%. Of 604 patients with clinical stages II and III, 267 (44.2%) had primary surgery; 337 (55.8%) received nCRT followed by TME. The 3-year LR rate was 3.9%, without significant differences between groups. In patients with clinical stages II and III who underwent primary surgery, 27.3% were diagnosed with pathological stage I. CONCLUSIONS: The results justify the restriction of nCRT to high-risk patients with rectal cancer classified by pretreatment MRI. Provided that a high-quality MRI diagnosis, TME surgery, and standardized examination of the resected specimen are performed, nCRT, with its adverse effects, costs, and treatment time can be avoided in more than 40% of patients with stage II or III rectal cancer with minimal risk of undertreatment. (clinicaltrials.gov NCT325649).

Limited Role for Routine Restaging After Neoadjuvant Therapy in Locally Advanced Rectal Cancer.

BACKGROUND: Although many patients with locally advanced rectal cancer undergo restaging imaging after neoadjuvant chemoradiotherapy and before surgery, the benefit of this practice is unclear. The purpose of this study was to examine the impact of reimaging on outcomes. MATERIALS AND METHODS: We performed a retrospective analysis of consecutive patients with stage 2 and 3 rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy between May 2005 and April 2018. Patient and disease characteristics, imaging, treatment, and oncologic outcomes were compared between those who underwent restaging and those who went directly to surgery. Predictors of outcomes and cost effectiveness of restaging were determined. RESULTS: Of 224 patients, 146 underwent restaging. Six restaged patients had findings leading to a change in management. There was no difference in freedom from recurrence (P = 0.807) and overall survival (P = 0.684) based on restaging. Pretreatment carcinoembryonic antigen level >3 ng/mL (P = 0.010), clinical T stage 4 (P = 0.016), and pathologic T4 (P = 0.047) and N2 (P = 0.002) disease increased the risk of death, whereas adjuvant chemotherapy decreased the risk of death (P < 0.001) on multivariate analysis. Disease recurrence was lower with pelvic exenteration (P = 0.005) and in females (P = 0.039) and higher with pathologic N2 (P = 0.003) and N3 (P = 0.002) disease. The average cost of reimaging is $40,309 per change in management; however, $45 is saved per patient when downstream surgical costs are considered. CONCLUSIONS: Imaging restaging after neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer rarely changes treatment and does not improve survival. In a subset of patients at higher risk for worse outcome, reimaging may be beneficial.

Assessment of T and N staging with MRI3T in lower and middle rectal cancer and impact on clinical strategy.

BACKGROUND: To determine the diagnostic accuracy of preoperative T/N stage using MRI in lower and middle rectal cancer patients and the impacts on clinical decision-making. PATIENTS AND METHODS: There were 354 patients recruited from May 2017 to February 2019. MRI was performed within 2 weeks before surgery. Histopathologic results were evaluated for the postoperative T/N stage and MRI diagnostic accuracy was assessed based on the postoperative histopathologic results. Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and Kappa values were used to evaluate MRI diagnostic accuracy and analysis consistency compared with postoperative histopathologic staging. RESULTS: Overall MRI diagnostic accuracy was 78.2% and 56.8% for T1-4 and N0-2 staging. The Kappa values were 0.625 and 0.323 for T1-4 and N0-2 staging, respectively. After combination, MRI diagnostic accuracy was 85% and 69.5% for T and N staging. The Kappa values were 0.693 and 0.4 for T and N staging. The diagnostic accuracy of MRI for treatment decision-making was 79.1%. CONCLUSION: MRI enables a highly accurate preoperative assessment of T stage but only a fairly accurate preoperative assessment of the N stage for rectal cancer with surgery. The diagnostic accuracy of MRI for treatment decision-making is promising.

Cost-effectiveness analysis of endocrine therapy alone versus partial-breast irradiation alone versus combined treatment for low-risk hormone-positive early-stage breast cancer in women aged 70 years or older.

PURPOSE: We performed a cost-effectiveness analysis of three strategies for the adjuvant treatment of early breast cancer in women age 70 years or older: an aromatase inhibitor (AI-alone) for 5 years, a 5-fraction course of accelerated partial-breast irradiation using intensity-modulated radiation therapy (APBI-alone), or their combination. METHODS: We constructed a patient-level Markov microsimulation from the societal perspective. Effectiveness data (local recurrence, distant metastases, survival), and toxicity data were obtained from randomized trials when possible. Costs of side effects were included. Costs were adjusted to 2019 US dollars and extracted from Medicare reimbursement data. Quality-adjusted life-years (QALY) were calculated using utilities extracted from the literature. RESULTS: The strategy of AI-alone ($12,637) was cheaper than both APBI-alone ($13,799) and combination therapy ($18,012) in the base case. All approaches resulted in similar QALY outcomes (AI-alone 7.775; APBI-alone 7.768; combination 7.807). In the base case, AI-alone was the cost-effective strategy and dominated APBI-alone, while combined therapy was not cost-effective when compared to AI-alone ($171,451/QALY) or APBI-alone ($107,932/QALY). In probabilistic sensitivity analyses, AI-alone was cost-effective at $100,000/QALY in 50% of trials, APBI-alone in 28% and the combination in 22%. Scenario analysis demonstrated that APBI-alone was more effective than AI-alone when AI compliance was lower than 26% at 5 years. CONCLUSIONS: Based on a Markov microsimulation analysis, both AI-alone and APBI-alone are appropriate options for patients 70 years or older with early breast cancer with small cost differences noted. A prospective trial comparing the approaches is warranted.

Relapsed Wilms' tumor in pediatric patients: challenges in low- to middle-income countries-a single-center experience.

BACKGROUND: Wilms' tumor (WT) affects one in 10,000 children and accounts for 5% of all childhood cancers. Although the overall relapse rate for children with WT has decreased to less than 15 %, the overall survival for patients with recurrent disease remains poor at approximately 50 %. The aim of the study to evaluate the outcome of relapsed Wilms' tumor pediatric patients treated at the National Cancer Institute (NCI), Egypt, between January 2008 and December 2015. RESULTS: One hundred thirty (130) patients diagnosed with WT during the study period, thirty (23%) patients had relapsed. The median follow up period was 22.3 months (range 3.6-140 months). The Overall Survival (OS) was 30.9% while the event-free survival (EFS) was 29.8% at a 5-year follow up period. Median time from diagnosis to relapse was 14.4 months. A second complete remission was attained in 18/30 patients (60%). The outcome of the 30 patients; 11 are alive and 19 had died. Three factors in our univariate analysis were prognostically significant for survival after relapse. The first was radiotherapy given after relapse (p = 0.012). The 5-year EFS and OS for the group that received radiotherapy were 41.9% versus 16.7% and 11.1% respectively for those that did not. The second was the state of lymph nodes among patients with local stage III (p = 0.004). Lastly, when risk stratification has been applied retrospectively on our study group, it proved to be statistically significant (p = 0.029). CONCLUSION: Among relapsed pediatric WT, radiotherapy improved survival at the time of relapse and local stage III with positive lymph nodes had the worst survival among other stage III patients.