Intraoperative Radiation Therapy as a Safe Alternative to Whole Breast Radiation for Treatment of Minimally Invasive Breast Cancers: A Retrospective Cohort Study.

BACKGROUND: Intraoperative radiation therapy (IORT) in select populations is a viable alternative to whole breast radiation therapy (WBRT) in the treatment of biopsy-proven localized invasive and non-invasive breast cancer. We aim to assess recurrence and complication rates following IORT in lumpectomy patients at a community hospital in Baltimore City. METHODS: An IRB-approved retrospective cohort study was conducted on consecutive cases of lumpectomy with IORT from 2013 through 2020 by a single surgeon. Patient demographics, tumor and operative characteristics, and complications were retrieved from electronic medical records. Primary outcomes were postoperative complications and local recurrence rates. RESULTS: The final cohort included 117 patients with mean follow-up time of 2.60 + 1.78 years. Mean age was 69.84 + 8.77 years. Thirty-three (28.21%) of patients developed a seroma. Odds of seroma formation were mildly significant for skin spacing [OR: 1.18, 95% CI: (1.02-1.37)] and balloon fill volume [1.04 (1.00-1.08)], but not for age, BMI, diabetes, former or current smoking status, history of WBRT, tumor size, or balloon size. Three (2.6%) patients had local recurrence. Odds of local recurrence were mildly significant for increased tumor size [1.14 (1.04-1.24)] and not significant for any other covariates. CONCLUSIONS: IORT exposure did not confer higher rates of complications and the local recurrence rate mirrored that of the general population undergoing lumpectomy and WBRT. This study demonstrates the need for equitable treatment options based on individual needs: IORT is a safe alternative to WBRT in certain subpopulations, especially those with physical, social, or personal limitations preventing participation in a 3- to 7-week time commitment of WBRT.

Surveillance With Serial Imaging and CA 19-9 Tumor Marker Testing After Resection of Pancreatic Cancer: A Single-Center Retrospective Study.

OBJECTIVES: Most patients receiving curative-intent surgery for pancreatic cancer will experience cancer recurrence. However, evidence that postoperative surveillance testing improves survival or quality of life is lacking. We evaluated the use and characteristics of surveillance with serial imaging and CA 19-9 tumor marker testing at an NCI-designated comprehensive cancer center. METHODS: We conducted a retrospective cohort study of patients who entered surveillance after curative-intent resection of pancreatic adenocarcinoma. We abstracted information from the electronic medical record about oncology office visits, surveillance testing (cross-sectional imaging and CA 19-9 tumor marker testing), and pancreatic cancer recurrence, with follow-up through 2 years after pancreatectomy. We conducted analyses to describe the use of surveillance testing and to characterize the sensitivity and specificity of CA 19-9 tumor marker testing for the identification of cancer recurrence. RESULTS: We identified 90 patients entering surveillance after pancreatectomy. CA 19-9 was the most frequently used surveillance test, followed by CT imaging. Forty-seven patients (52.2%) experienced recurrence within two years of pancreatectomy. Recurrence risk was 58.8% versus 31.8% in patients with elevated versus normal CA 19-9 at diagnosis ( P =0.03). Elevated CA 19-9 at any point during surveillance was significantly associated with 2-year recurrence risk ( P <0.001). Elevated CA 19-9 had a sensitivity of 83% (95% CI 0.72-0.95) and specificity of 87% (0.76-0.98) for identification of recurrence within 2 years of pancreatectomy. CONCLUSIONS: CA 19-9 demonstrates clinical validity for identifying recurrence of pancreatic cancer during surveillance. Surveillance approaches with reduced reliance on imaging should be prospectively evaluated.

Using Machine Learning to Leverage Biomarker Change and Predict Colorectal Cancer Recurrence.

PURPOSE: The risk of colorectal cancer (CRC) recurrence after primary treatment varies across individuals and over time. Using patients' most up-to-date information, including carcinoembryonic antigen (CEA) biomarker profiles, to predict risk could improve personalized decision making. METHODS: We used electronic health record data from an integrated health system on a cohort of patients diagnosed with American Joint Committee on Cancer stage I-III CRC between 2008 and 2013 (N = 3,970) and monitored until recurrence or end of follow-up. We addressed missingness in recurrence outcomes and longitudinal CEA measures, and engineered CEA features using current and past biomarker values for inclusion in a risk prediction model. We used a discrete time Superlearner model to evaluate various algorithms for predicting recurrence. We evaluated the time-varying discrimination and calibration of the algorithms and assessed the role of individual predictors. RESULTS: Recurrence was documented in 448 (11.3%) patients. XGBoost with depth = 1 (XGB-D1) predicted recurrence substantially better than all other algorithms at all time points, with AUC ranging from 0.87 (95% CI, 0.86 to 0.88) at 6 months to 0.94 (95% CI, 0.92 to 0.96) at 54 months. The only variable used by XGB-D1 was 6-month change in log CEA. Predicted 1-year risk of recurrence was nearly zero for patients whose log CEA did not increase in the last 6 months, between 12.2% and 34.1% for patients whose log CEA increased between 0.10 and 0.40, and 43.6% for those with a log CEA increase >0.40. Compared with XGB, penalized regression approaches (lasso, ridge, and elastic net) performed poorly, with AUCs ranging from 0.58 to 0.69. CONCLUSION: A flexible, machine learning approach that incorporated longitudinal CEA information yielded a simple and high-performing model for predicting recurrence on the basis of 6-month change in log CEA.

Advances in radiation therapy for testicular seminoma.

PURPOSE: Novel techniques and advances in radiation therapy (RT) have been explored to treat testicular seminoma, a highly radiosensitive and curable histology. We evaluated the historical and current indications for radiation therapy (RT) in testicular seminoma. METHODS: A narrative literature review was performed. Studies of RT for testicular seminoma were included. Additionally, recent trials testing the use of combination or surgical therapies for clinical stage (CS) II were included. Search parameters included radiation therapy, testicular seminoma, surgery, and chemoradiation. Parameters and outcomes assessed were progression-free survival (PFS), overall survival (OS), acute toxicities, long-term sequelae, and rates of secondary malignancies. RESULTS: Practice defining and changing studies in the use or omission of radiation therapy for testicular seminoma were identified along with resultant changes in National Comprehensive Cancer Network (NCCN) and European guidelines. Recent trials in combined chemoradiation and upfront surgical approaches to CS II disease were reviewed. CONCLUSION: RT has historically been used as adjuvant treatment for CS I disease and is highly effective at treating CS II (A/B) testicular seminoma. The drive to maintain therapeutic efficacy and reduce acute and long-term side effects, namely secondary malignancies, is being tested using new radiation technologies, combined modality therapy in the form of chemoradiation and with upfront surgical approaches. Also, as guidelines now "strongly prefer" surveillance instead of adjuvant RT for CS I disease, the current CS II population comprises patients presenting with CS II disease ("de novo") and those who present with CSII after relapsing post orchiectomy for CS I ("relapsed"). Emerging evidence suggests that these two groups have different outcomes with respect to RT and chemoradiation. Consequently, future trials may need to sub-stratify according to these groups.

Brachytherapy With 15- Versus 20-mm Ruthenium 106 Plaques Without Verification of Plaque Position Is Associated With Local Tumor Recurrence and Death in Posterior Uveal Melanoma.

PURPOSE: Brachytherapy with episcleral plaques is the most common primary tumor treatment for uveal melanoma. This study aimed to compare the risk of tumor recurrence and metastatic death between 2 frequently used ruthenium 106 plaque designs: CCB (20.2 mm) and CCA (15.3 mm). METHODS AND MATERIALS: Data were obtained from 1387 consecutive patients treated at St. Erik Eye Hospital, Stockholm, Sweden between 1981 and 2022 (439 with CCA and 948 with CCB plaques). During the period, scleral transillumination was performed to delineate tumor margins before plaque insertion, but accurate plaque positioning was not verified after scleral attachment, and no minimum scleral dose was used. RESULTS: Patients treated with CCA plaques had smaller tumors than those treated with CCB plaques (mean diameter, 8.6 vs 10.5 mm; P < .001). There were no differences in patient sex, age, tumor distance to the optic disc, tumor apex dose, dose rate, or in rates of ciliary body involvement, eccentric plaque placement, or adjunct transpupillary thermotherapy (TTT). The average difference between plaque and tumor diameter was greater with the CCB plaque, and a smaller difference was an independent predictor of tumor recurrence. The 15-year incidence of tumor recurrence was 28% and 15% after treatment with CCA and CCB plaques, respectively (competing risk analysis, P < .001). Multivariate Cox regression analysis revealed a lower risk for tumor recurrence with CCB plaques (hazard ratio, 0.50). Similarly, patients treated with CCB plaques had a lower risk for uveal melanoma-related mortality (hazard ratio, 0.77). The risk for either outcome was not lower for patients treated with adjunct TTT. Uni- and multivariate time-dependent Cox regressions demonstrated that tumor recurrence was associated with uveal melanoma-related and all-cause mortality. CONCLUSIONS: Compared with 20-mm plaques, brachytherapy with 15-mm ruthenium plaques is associated with a higher risk for tumor recurrence and death. These adverse outcomes may be avoided by increasing safety margins and implementing effective methods to verify accurate plaque positioning.

Bilaterality, not multifocality, is an independent risk factor for recurrence in low-risk papillary thyroid cancer.

BACKGROUND: The impact of multifocality and bilaterality on recurrence in patients with low-risk papillary thyroid cancer (PTC) is relevant when considering patients for a de-escalated treatment strategy: hemithyroidectomy instead of total thyroidectomy followed with or without radioactive iodine. This study aims to analyze contralateral tumor probability in patients treated for low-risk PTC and assess multifocality and bilaterality as possible predictors for recurrence. METHODS: Patients with low-risk PTC treated with total thyroidectomy followed with or without radioactive iodine in the Netherlands between 2005 and 2015 were included in this study. Patients were identified from the Netherlands Comprehensive Cancer Organization (IKNL) and linked with the nationwide network and registry of Pathology in the Netherlands (PALGA). Contralateral tumor probability and recurrence were assessed. RESULTS: Of 791 included patients, 41.8% (331 of 791) had multifocal disease, with 68.9% (228 of 331) of those patients having bilateral disease. The contralateral tumor probability after hemithyroidectomy was 24.6% (150 of 610) for patients with unifocal disease and 43.1% (78 of 181) for patients with multifocal disease. We found a higher trend of recurrence in patients with bilateral disease, regardless of multifocality: in patients with contralateral disease after precompletion diagnosed unifocal disease 7.3% (11 of 150) had recurrent disease, and patients without contralateral disease after precompletion diagnosed multifocal disease 1.9% (2 per 103) had recurrence. Cox regression analysis showed that bilaterality (hazard ratio = 3.621, 95% confidence interval = 1.548 to 8.471) was the sole statistically significant risk factor for recurrence. CONCLUSION: Low recurrence rates are found in patients with either multifocal or bilateral disease with low-risk PTC. Bilaterality should be taken into account when considering these patients for de-escalated treatment strategy.

Outcomes of DCIS treated with breast conserving surgery without radiotherapy on recurrence, survival, and health-related quality of life.

BACKGROUND: Sector resection for Ductal Carcinoma in Situ (DCIS) allows wide excision without compromising breast shape. There are concerns that radiotherapy for some DCIS after sector resection is unnecessary and reduces patient satisfaction and quality of life without affecting survival. This study aimed to investigate whether women with DCIS managed with sector resection without radiotherapy had acceptable rates of recurrence and health-related quality of life outcomes. METHODS: Retrospective study of patients who underwent sector resection for DCIS without adjuvant radiotherapy from 1992 to 2021. Tumour size, grade, necrosis, margins, follow up and time to ipsilateral recurrence was recorded. Patients were posted a BREAST-Q to assess health-related quality of life. RESULTS: One hundred and thirty-eight patients were treated for pure DCIS by two surgeons from 1992 to 2018. One hundred and sixteen patients underwent sector resection, 22 had mastectomy. Average age 61 years. Mean follow up 9.14 years. Recurrence rate after sector resection was 18.97%. 55% were DCIS. Annualized recurrence rate was 2.07%. There were no cancer-related deaths. BREAST-Q completion rate was 44%. Satisfaction with breasts, physical, psychosocial, and sexual well-being scores were significantly higher than normative Australian values and a mixed cohort of women who underwent breast conserving surgery with radiotherapy. CONCLUSION: DCIS can be safely managed with sector resection without radiotherapy and regular long-term follow up. This approach results in low annualized recurrence rates, high levels patient satisfaction and health-related quality of life and should be considered a safe alternative for patients with DCIS to minimize morbidity without affecting cancer survival.

Intraoperative Radiation Therapy: A Large Integrated Health Care System's Approach and Outcomes.

Introduction Intraoperative radiation therapy (IORT) may not be as effective in the community compared with clinical trials. Methods The authors reviewed data from the electronic health records of patients who received IORT between February 2014 and February 2020 at a single center within a large integrated health care system. The primary outcome was ipsilateral breast tumor recurrence. Results Of 5731 potentially eligible patients, 245 (4.3%) underwent IORT (mean age: 65.4 ± 0.4 years; median follow-up time: 3.5 years ± 2.2 months). According to the American Society for Radiation Oncology's accelerated partial breast irradiation guidelines based on final pathology, 51% of patients were suitable candidates for IORT, 38.4% were cautionary, and 10.6% were unsuitable. For adjuvant therapy, 6.5% had consolidative whole breast irradiation, and 66.4% received endocrine treatment. At the median follow-up time of 3.5 years, overall ipsilateral breast tumor recurrence was 3.7%. Recurrences tended to be more frequent in patients who refused or did not complete endocrine treatment than in those who received it (7.4% vs 1.9%, p = 0.07). The complication rate was 14.7%, with seroma being the most common (8.2%). Discussion The IORT ipsilateral breast tumor recurrence rate of 3.7% confirms a higher-than-expected rate compared to randomized clinical trials, possibly due to less compliance with endocrine therapy. Conclusion The authors subsequently revised their IORT protocol to require endocrine treatment as a part of the IORT treatment plan and to strongly recommend adjuvant whole breast irradiation for all patients deemed cautionary or unsuitable for IORT according to the American Society for Radiation Oncology's accelerated partial breast irradiation guidelines.

Surgical resection margin for T3-T4 primary acral melanoma: a multicenter retrospective cohort study.

Although the National Comprehensive Cancer Network (NCCN) guidelines include clear recommendations for the appropriate resection margins in non-acral cutaneous melanoma, the required margin for acral melanoma is controversial. In this retrospective study, we aimed to investigate whether narrow-margin excision is warranted for thick acral melanoma. Records from 277 melanoma patients with stage T3-T4 disease who underwent radical surgery in three centers in China from September 2010 to October 2018 were reviewed. Clinicopathologic data, including age, gender, excision margin (1-2 cm versus ≥ 2 cm), Clark level, Breslow thickness, ulceration, N stage and adjuvant therapy, were included for survival analysis. The patients were followed up until death or March 31, 2021. Log-rank and Cox regression analyses were used to identify prognostic factors for overall survival (OS), disease-free survival (DFS) and local and in-transit recurrence-free survival (LITRFS). Among all enrolled patients, 207 (74.7%) had acral melanoma, and 70 (25.3%) had non-acral cutaneous melanoma. No significant difference in baseline characteristics was identified between non-acral and acral melanoma, except for age (p = 0.004), gender (p = 0.009) and ulceration (p = 0.048). In non-acral melanoma, a resection margin of 1-2 cm was a poor independent prognostic factor for OS [p = 0.015; hazard ratio (HR) (95% CI), 0.26 (0.009-0.77)] and LITRFS [p = 0.013; HR (95% CI), 0.19 (0.05-0.71)] but not for DFS [p = 0.143; HR (95% CI), 0.51 (0.21-1.25)]. Forty-three (20.8%) patients in the acral melanoma group had a 1-2-cm resection margin. The resection margin was not correlated with patients' OS (p = 0.196 by log-rank analysis, p = 0.865 by multivariate survival analysis), DFS (p = 0.080 by log-rank analysis, p = 0.758 by multivariate survival analysis) or LITRFS (p = 0.354 by log-rank analysis) in acral melanoma. As recommended in the NCCN guidelines, a resection margin ≥ 2 cm is required for non-acral cutaneous melanoma. Meanwhile, a narrow resection margin (1-2 cm) may be safe for patients with acral melanoma.

Prolonged Survival in Peritoneal Metastatic Appendiceal Carcinoma Patients Treated With Combined Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Primary treatment for peritoneal dissemination of appendiceal cancer is the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The endpoints were overall survival and evaluation of prognostic factors. METHODS: Clinicopathological and treatment-related factors were obtained from a prospective database. A total of 84 patients, 55 (65%) primary and 29 (35%) recurrent malignant appendiceal carcinomas with synchronous and metachronous peritoneal metastases, underwent multimodal treatment between 2011 and 2021. The endpoints of the study were overall survival and evaluation of prognostic factors. RESULTS: The median follow-up was 4.8 y; the mean age was 54.5 y (range 25-77), with a sex distribution of 69% female and 31% male. The mean peritoneal cancer index was 11.3. The proportion of mucinous, intestinal-type, signet ring cell, and goblet cell carcinoma was 56%, 23%, 11%, and 10%, respectively. The 5-y survival rate of the whole cohort was 56.7%. In primary and recurrent diseases, the overall median survival was 8.4 and 4.9 y. Significantly improved survival was detected after complete cytoreduction resection (hazard ratio [HR] for CCR-2 versus CCR-0: 9.388, 95% confidence interval [CI] 3.026-29.124, P = 0.001) and initial local operation with undelayed admission to the center (HR 0.262, 95% CI 0.089-0.773; P = 0.015). The five independent factors in Kaplan-Meier analysis and univariable Cox regression analysis associated with significant adverse survival were cancer antigen (CA) 19-9 over 37 IU/mL, signet ring cell and intestinal-type histology, positive nodal status, grading, and peritoneal cancer index >20. Neoadjuvant chemotherapy administration did not impact survival (HR 1.220, 95% CI 0.612-2.432, P = 0.571). CONCLUSIONS: With multimodal treatment, prolonged survival is attainable in stage IV primary and recurrent appendiceal carcinoma with peritoneal dissemination. Direct referral to specialized centers after confirmation of peritoneal metastasis is recommended because prompt definitive treatment may significantly improve survival.

Association of Surgical Timing with Outcomes in Early Stage Lung Cancer.

BACKGROUND: Optimal time to surgery for lung cancer is not well established. We aimed to assess whether time to surgery correlates with outcomes. METHODS: We assessed patients 18-84 years old who were diagnosed with stage I/II lung cancer at our integrated healthcare system from 2009 to 2019. Time to surgery was defined to start with disease confirmation (imaging or biopsy) prior to the surgery scheduling date. Outcomes of unplanned return to care within 30 days of lung cancer surgery, all-cause mortality, and disease recurrence were compared based on time to surgery before and after 2, 4, and 12 weeks. RESULTS: Of 2861 included patients, 70% were over 65 years old and 61% were female. Time to surgery occurred in 1-2 weeks for 6%, 3-4 weeks for 31%, 5-12 weeks for 58%, and 13-26 weeks for 5% of patients. Patients with time to surgery > 4 (vs. ≤ 4) weeks had greater risk of both death (hazard ratio (HR) 1.18, 95% confidence interval (CI) 1.00-1.39) and recurrence (HR 1.33, 95% CI 1.10-1.62). Associations were not statistically significant when dichotomizing time to surgery at 2 or 12 weeks for death (2 week HR 1.23, 95% CI 0.93-1.64; 12 week HR 1.35, 95% CI 0.97-1.88) and recurrence (2 week HR 1.54, 95% CI 0.85-2.80; 12 week HR 2.28, 95% CI 0.80-6.46). CONCLUSIONS: Early stage lung cancer patients with time to surgery within 4 weeks experienced lower rates of recurrence. Optimal time to surgical resection may be shorter than previously reported.

Allogeneic hematopoietic cell transplantation in patients with a hematologic malignancy and a prior history of breast cancer.

PURPOSE: To compare the outcome of allogeneic stem cell transplantation for myeloid malignancies in breast cancer survivors to a contemporaneous control group. METHODS: Medical records of all patients with a history of breast cancer who received allogeneic stem cell transplants at a single, tertiary referral Comprehensive Cancer Center between 2002 and 2019 were reviewed. Transplant outcomes were compared to 289 control patients without a history of breast cancer from the same time period. Main outcomes included survival, disease-free survival, non-relapse mortality, relapse or progression of hematologic malignancy, and incidence of recurrent breast cancer after hematopoietic cell transplantation. Comparisons between women with a history of breast cancer and controls utilized propensity score weighting to balance patient characteristics. RESULTS: Forty women, ages 30-74 years, with a history of breast cancer received an allogeneic hematopoietic cell transplant for a hematologic malignancy between December 2002 and February 2019. Twelve of the 40 patients are alive with a median survival of 7.4 years (range, 1.9-16.8 years). None of the patients had evidence of recurrent breast cancer prior to death or date of last contact. In multivariable Cox models, all transplant outcomes were similar between the patients and the control group with hematopoietic cell transplant comorbidity score as the most important confounding factor for adjustment in these models. CONCLUSION: A history of treated breast cancer should not exclude patients from consideration for allogeneic hematopoietic cell transplantation.

Complete Margin Assessment Versus Sectional Assessment in Surgically Excised High-Risk Keratinocyte Carcinomas: A Systematic Review and Meta-Analysis.

BACKGROUND: Keratinocyte carcinomas (KCs) are the most diagnosed cancers worldwide and are commonly excised via complete margin assessment (CMA) or excision with sectional assessment (SA). National Comprehensive Cancer Network guidelines encourage CMA for KC with high-risk features. OBJECTIVE: To systematically compare recurrence outcomes for CMA vs SA in high-risk KC based on National Comprehensive Cancer Network guidelines criteria. MATERIALS AND METHODS: EMBASE and MEDLINE were searched for articles reporting recurrences of high-risk KC undergoing excision using CMA or SA. High-risk KCs were defined as recurrent, having perineural invasion (PNI), or basal cell carcinomas (BCC) with aggressive histology. Chi-squared tests and risk ratios evaluated differences between CMA and SA groups, and a random-effects meta-analysis was performed. RESULTS: Twenty-eight studies met inclusion criteria. Pooled percentages of locoregional recurrences were significantly lower with CMA vs SA for all KCs (3.9% [95% CI: 2.9-4.9] vs 13.5% [7.7, 19.2, p = .001]), cutaneous squamous cell carcinoma with PNI (9.8% [5.4-14.1] vs 32.0% [25.0-39.0], p < .001), and recurrent BCC (4.4% [2.9-5.9] vs 11.9% [8.0-15.8], p < .001). CONCLUSION: For high-risk KCs, recurrence risk was over 3-times greater with SA compared with CMA. Expanded access to CMA for high-risk KC is likely to reduce recurrence risk and improve clinical outcomes.

The Added Value of Baseline Health-Related Quality of Life in Predicting Survival in High-Risk Prostate Cancer Patients Following Radical Prostatectomy.

PURPOSE: Several studies have shown baseline health-related quality of life to be a valuable prognostic indicator of survival outcomes for various cancer entities in the metastatic setting. To date, there is no evidence regarding the prognostic value of baseline health-related quality of life for patients undergoing radical prostatectomy due to localized prostate cancer. MATERIALS AND METHODS: A total of 1,029 patients with high-risk prostate cancer according to National Comprehensive Cancer Network® risk stratification and prospectively assessed baseline health-related quality of life prior to radical prostatectomy were identified. Patients were stratified by global health status domain of the QLQ-C30 questionnaire. Oncologic endpoints were biochemical recurrence-free survival and metastasis-free survival. Multivariable Cox regression models were performed to assess prognostic significance of baseline global health status on survival outcomes. Harrell's discrimination C-index was applied to calculate the predictive accuracy of the model and previously described risk stratification models. Decision curve analysis was applied to test the clinical net benefit associated with adding global health status to our multivariable model (P < .05). RESULTS: Median follow-up was 43 months. In multivariable analysis, global health status was confirmed as an independent predictor for increased biochemical recurrence-free survival (HR .97, 95% CI .96-.99; P = .001) and metastasis-free survival (HR .96, 95% CI .93-.99; P = .013), indicating a relative risk reduction of 2.9% for biochemical recurrence-free survival and 3.7% for metastasis-free survival per 1-point increase of baseline global health status. Adding baseline health-related quality of life to our model and to the Cancer of the Prostate Risk Assessment and National Comprehensive Cancer Network score improved discrimination in predicting biochemical recurrence-free survival and metastasis-free survival of the respective models. Decision curve analysis revealed a net benefit over all threshold probabilities. CONCLUSIONS: Our findings highlight baseline health-related quality of life to be a valuable and robust prognostic factor for patients with localized high-risk prostate cancer prior to radical prostatectomy. Baseline health-related quality of life increased prognostic accuracy of biochemical recurrence-free survival and metastasis-free survival.

Outcomes of Papillary Thyroid Microcarcinoma Presenting with Palpable Lateral Lymphadenopathy.

Purpose: Papillary thyroid microcarcinoma (PTMC) is typically indolent in nature, allowing management with active surveillance protocols. Occasionally, a more aggressive phenotype can present and may lead to poor outcomes such as patients presenting with clinically significant lateral lymphadenopathy (cN1b). Prior analysis of the outcomes of this cohort is largely from papillary thyroid cancer (PTC) (>1 cm) or from institutions where use of radioactive iodine (RAI) is limited. Hence, we aim to describe the outcomes of patients with PTMC who presented with palpable cN1b disease, treated with total thyroidectomy and RAI. Methodology: We performed a retrospective cohort study. Outcomes of patients with PTMC who presented with palpable lateral lymph node (LN) metastases (microPTC cN1b) treated between 1997 and 2020 at Royal North Shore Hospital were compared with two control groups' outcomes: patients with clinically detected PTMC without evidence of involved LNs (microPTC cN0) and with larger PTC (>10 mm) who presented with palpable lateral lymphadenopathy (larger PTC cN1b). We assessed clinicopathological variables, postoperative risk stratification, rates of disease recurrence, reoperative surgery, and structural disease-free survival (DFS). Results: In total, 1534 PTMCs were diagnosed following thyroid surgery in the study period; of these, 157 (10%) were clinically detected microPTC cN0 and 26 microPTC cN1b (1.7%). There were 138 patients in the larger PTC cN1b control group. All cN1b patients were treated with total thyroidectomy and adjuvant RAI. Mean size of the largest LN deposit was similar between the microPTC cN1b and larger PTC cN1b groups (23 vs. 27 mm, p = 0.11). Patients with microPTC cN1b were more likely to have biochemical or structural persistence or recurrence compared with microPTC cN0 (19%, 5/26 vs. 3.8%, 6/157, p = 0.002) but less likely than larger PTC cN1b patients (19%, 5/26 vs. 42%, 58/138, p = 0.04). All patients in the microPTC cN1b group who had an excellent response to initial therapy (85%, 22/26) were disease free at last follow-up. The rate of reoperation was similar for the microPTC cN1b and microPTC cN0 groups (4%, 1/26 vs. 2%, 3/157, p = 0.461) and significantly lower than the larger PTC cN1b group (4%, 1/26 vs. 26%, 36/138, p = 0.002). Five-year DFS estimates were significantly better for microPTC cN1b patients than for larger PTC cN1b patients (94% vs. 59%, p = 0.001). Conclusions: MicroPTC cN1b patients treated with thyroidectomy and adjuvant RAI have inferior clinical outcomes compared with microPTC cN0 patients but have better outcomes than their larger PTC cN1b counterparts with respect to disease persistence and recurrence. Response to initial therapy provides valuable prognostication in microPTC cN1b patients: if these patients had an excellent response to initial treatment, they achieved long-term DFS in this series.

Early stage breast cancer follow-up in real-world clinical practice: the added value of cell free circulating tumor DNA.

PURPOSE: Physical examinations and annual mammography (minimal follow-up) are as effective as laboratory/imaging tests (intensive follow-up) in detecting breast cancer (BC) recurrence. This statement is now challenged by the availability of new diagnostic tools for asymptomatic cases. Herein, we analyzed current practices and circulating tumor DNA (ctDNA) in monitoring high-risk BC patients treated with curative intent in a comprehensive cancer center. PATIENTS AND METHODS: Forty-two consecutive triple negative BC patients undergoing neoadjuvant therapy and surgery were prospectively enrolled. Data from plasma samples and surveillance procedures were analyzed to report the diagnostic pattern of relapsed cases, i.e., by symptoms, follow-up procedures and ctDNA. RESULTS: Besides minimal follow-up, 97% and 79% of patients had at least 1 non-recommended imaging and laboratory tests for surveillance purposes. During a median follow-up of 5.1(IQR, 4.1-5.9) years, 13 events occurred (1 contralateral BC, 1 loco-regional recurrence, 10 metastases, and 1 death). Five recurrent cases were diagnosed by intensive follow-up, 5 by symptoms, and 2 incidentally. ctDNA antedated disseminated disease in all evaluable cases excepted two with bone-only and single liver metastases. The mean time from ctDNA detection to suspicious findings at follow-up imaging was 3.81(SD, 2.68), and to definitive recurrence diagnosis 8(SD, 2.98) months. ctDNA was undetectable in the absence of disease and in two suspected cases not subsequently confirmed. CONCLUSIONS: Some relapses are still symptomatic despite the extensive use of intensive follow-up. ctDNA is a specific test, sensitive enough to detect recurrence before other methods, suitable for clarifying equivocal imaging, and exploitable for salvage therapy in asymptomatic BC survivors.

Patterns of Medical Care Cost by Service Type for Patients With Recurrent and De Novo Advanced Cancer.

OBJECTIVES: There is limited knowledge about the cost patterns of patients who receive a diagnosis of de novo and recurrent advanced cancers in the United States. METHODS: Data on patients who received a diagnosis of de novo stage IV or recurrent breast, colorectal, or lung cancer between 2000 and 2012 from 3 integrated health systems were used to estimate average annual costs for total, ambulatory, inpatient, medication, and other services during (1) 12 months preceding de novo or recurrent diagnosis (preindex) and (2) diagnosis month through 11 months after (postindex), from the payer perspective. Generalized linear regression models estimated costs adjusting for patient and clinical factors. RESULTS: Patients who developed a recurrence <1 year after their initial cancer diagnosis had significantly higher total costs in the preindex period than those with recurrence ≥1 year after initial diagnosis and those with de novo stage IV disease across all cancers (all P < .05). Patients with de novo stage IV breast and colorectal cancer had significantly higher total costs in the postindex period than patients with cancer recurrent in <1 year and ≥1 year (all P < .05), respectively. Patients in de novo stage IV and those with recurrence in ≥1 year experienced significantly higher postindex costs than the preindex period (all P < .001). CONCLUSIONS: Our findings reveal distinct cost patterns between patients with de novo stage IV, recurrent <1-year, and recurrent ≥1-year cancer, suggesting unique care trajectories that may influence resource use and planning. Future cost studies among patients with advanced cancer should account for de novo versus recurrent diagnoses and timing of recurrence to obtain estimates that accurately reflect these care pattern complexities.

Hospital readmissions for patients with prostate cancer are higher after radiotherapy than after prostatectomy.

PURPOSE: To compare hospital readmissions, biochemical recurrence rates, incidence of metastasis, and cancer-specific and overall mortality for prostate cancer patients undergoing radiotherapy vs. radical prostatectomy. The secondary outcome was to identify patient and disease characteristics affecting physician's choice of either therapy. MATERIALS AND METHODS: A total of 297 patients diagnosed with prostate cancer between 2008 and 2014 were identified from a single academic center's cancer database. Clinical information including age, ethnicity, comorbidities, prostate-specific antigen, Gleason score, stage, National Comprehensive Cancer Network (NCCN) risk group, biochemical recurrence, hospital readmissions, and survival outcomes were gathered and analyzed from ambulatory medical records until 2018. RESULTS: Patients selected for radiotherapy were older and had more comorbidities and NCCN high-risk disease. Biochemical recurrence was higher after radical prostatectomy for locally advanced disease, 59.3% vs. 20.0% (p<0.001), favoring radiotherapy. Hospital readmission was higher for patients with locally advanced disease undergoing radiotherapy, 48.6% vs. 18.5% (p=0.002), and 35.2% vs. 19.7% (p=0.044) for those with localized disease, with most of these readmissions occurring 24 months after the initial therapy. Radiation proctitis and colitis were the most common complications after radiotherapy and accounted for 46.3% of readmissions. CONCLUSIONS: Selection of patients for radiotherapy instead of surgery was influenced by age, significant comorbidities, and NCCN high-risk disease. The incidence of treatment- or cancer-related hospital readmissions was significantly higher for patients undergoing radiotherapy compared with radical prostatectomy, especially for those with locally advanced prostate cancer. This information may be useful in guiding a patient's choice of therapy.

Blood Salvage and Autotransfusion With Single Leukoreduction Does Not Increase the Risk of Tumor Recurrence After Liver Transplantation for Advanced Hepatocellular Carcinoma.

OBJECTIVE: The aim of this study was to determine whether autotransfusion of salvaged blood with single leukoreduction is associated with post-transplant tumor recurrence in patients with advanced hepatocellular carcinoma (HCC). BACKGROUND: Previous studies have consistently demonstrated the safety of autotransfusion of salvaged and leukoreduced blood during liver transplantation for HCC. However, the effects of this technique remained unknown for advanced HCC. METHODS: Of 349 patients who underwent living donor liver transplantation for advanced HCC: 74 of 129 without autotransfusion were matched with 74 of 220 with autotransfusion using propensity score based on tumor biology, allogeneic transfusion, and others. Survival analysis was performed with death as a competing risk event. The primary outcome was HCC recurrence. RESULTS: Recipients in autotransfusion group received 811 (497-1247) mL of salvaged blood with single leukoreduction. In the matched cohort, cumulative overall recurrence probability at 1/2/5 years after transplantation was 24.6%/ 38.3%/39.7% for nonautotransfusion group and 16.2%/23.1%/32.5% for autotransfusion group. There were no significant differences between the 2 groups in overall recurrence [hazard ratio (HR) = 0.72 (0.43-1.21)], intrahepatic recurrence [HR = 0.70 (0.35-1.40)], and extrahepatic recurrence [HR = 0.82 (0.46-1.47)]. Also, there were no significant differences in overall death [HR = 0.57 (0.29-1.12)], HCC-related death [HR = 0.59 (0.29-1.20)], and HCC-unrelated death [HR = 0.48 (0.09-2.65)]. CONCLUSIONS: When allogeneic transfusion was matched, autotransfusion was not significantly related to HCC recurrence, with more favorable probabilities for autotransfusion, in patients with advanced HCC. Thus, blood salvage and autotransfusion could be safely used with single leukoreduction, without double-filtered leukoreduction, during liver transplantation for HCC with potential benefits from avoiding allogeneic red blood cell transfusion.

Organ Preservation in Patients with Rectal Cancer Treated with Total Neoadjuvant Therapy.

BACKGROUND: Retrospective studies suggest that watch-and-wait is a safe alternative to total mesorectal excision in selected patients with a clinical complete response after chemoradiotherapy. OBJECTIVE: This study aimed to determine the proportion of patients with rectal cancer who may benefit from watch-and-wait. DESIGN: This study is a retrospective analysis of data from prospectively maintained databases. SETTING: This study was conducted at a comprehensive cancer center. PATIENTS: Consecutive patients with stage II or III rectal adenocarcinoma who were treated with total neoadjuvant therapy using induction chemotherapy between 2012 and 2019 under the care of the same surgeon were included. INTERVENTION: Induction-type total neoadjuvant therapy consisted of 8 cycles of leucovorin-fluorouracil-oxaliplatin or 5 cycles of capecitabine-oxaliplatin before chemoradiotherapy. Patients with a clinical complete response were offered watch-and-wait, and patients with residual tumor were offered total mesorectal excision. MAIN OUTCOMES AND MEASURES: Tumor response was assessed with a digital rectal examination, endoscopy, and MRI. Patient characteristics and recurrence-free survival were compared between the watch-and-wait group and the total mesorectal excision group. RESULTS: A total of 88 patients were included in the analysis. One (1%) died during neoadjuvant therapy. Fifty-five patients (62.5%) had an incomplete clinical response and underwent surgery, 10 (18%) of the 55 developed distant metastasis, and 3 (5%) developed local recurrence. The remaining 32 patients (36.3%) had a clinical complete response and underwent watch-and-wait. On average, patients in the watch-and-wait group were older and had smaller, more distal tumors compared with patients in the surgery group. The median radiation dose, number of chemotherapy cycles, rate of adverse events, and length of follow-up did not differ substantively between the total mesorectal excision group and the watch-and-wait group. In the watch-and-wait group, 2 (6%) patients developed tumor regrowth, and one of them had distant metastasis. Recurrence-free survival was significantly higher in the watch-and-wait group. LIMITATIONS: Generalizability, sample size, and follow-up duration were limitations of this study. CONCLUSIONS: Approximately one-third of patients with stage II or III rectal cancer can benefit from a watch-and-wait approach with the aim of preserving the rectum if treated with induction-type total neoadjuvant therapy and followed by an experienced multidisciplinary team. See Video Abstract at http://links.lww.com/DCR/B688. CONSERVACIN DE RGANOS EN PACIENTES CON CNCER DE RECTO TRATADOS CON TERAPIA NEOADYUVANTE TOTAL: ANTECEDENTES:Estudios retrospectivos sugieren que observar y esperar es una alternativa segura a la escisión mesorrectal total en pacientes seleccionados con una respuesta clínica completa después de la quimiorradioterapia.OBJETIVO:Determinar la proporción de pacientes con cáncer de recto que pueden beneficiarse de observar y esperar.DISEÑO:Análisis retrospectivo de datos de bases de datos mantenidas de forma prospectiva.ESCENARIO:Centro Oncológico Integral.PACIENTES:Pacientes consecutivos con adenocarcinoma de recto en estadio II o III tratados con TNT utilizando quimioterapia de inducción entre 2012 y 2019 bajo el cuidado del mismo cirujano.INTERVENCIÓN:La terapia neoadyuvante total de tipo inducción consistió en ocho ciclos de leucovorín-fluorouracilo-oxaliplatino o cinco ciclos de capecitabina-oxaliplatino antes de la quimiorradioterapia. A los pacientes con una respuesta clínica completa se les ofreció observar y esperar, y a los pacientes con tumor residual se les ofreció la escisión mesorrectal total.PRINCIPALES RESULTADOS Y MEDIDAS:La respuesta del tumor se evaluó con un tacto rectal, endoscopia y resonancia magnética. Se compararon las características de los pacientes y la supervivencia libre de recurrencia entre el grupo de observación y espera y el grupo de escisión mesorrectal total.RESULTADOS:Se incluyó en el análisis a un total de 88 pacientes. Uno (1%) murió durante la terapia neoadyuvante. Cincuenta y cinco pacientes (62.5%) tuvieron una respuesta clínica incompleta y se sometieron a cirugía; 10 (18%) de los 55 desarrollaron metástasis a distancia y 3 (5%) desarrollaron recidiva local. Los 32 pacientes restantes (36.3%) tuvieron una cCR (respuesta clínica completa) y se sometieron a observar y esperar. En promedio, los pacientes del grupo de observación y espera eran mayores y tenían tumores más pequeños y distales en comparación con el grupo de cirugía. La dosis mediana de radiación, el número de ciclos de quimioterapia, la tasa de eventos adversos y la duración del seguimiento no difirieron sustancialmente entre el grupo de escisión mesorrectal total y el grupo de observación y espera. En el grupo de observación y espera, 2 (6%) pacientes desarrollaron recrecimiento del tumor y uno de ellos tuvo metástasis a distancia. La supervivencia libre de recurrencia fue significativamente mayor en el grupo de observación y espera.LIMITACIONES:Generalizabilidad, tamaño de la muestra, duración del seguimiento.CONCLUSIONES:Aproximadamente un tercio de los pacientes con cáncer de recto en estadio II o III pueden beneficiarse de un abordaje de observación y espera con el objetivo de preservar el recto si se tratan con terapia neoadyuvante total de tipo inducción y son seguidos por un equipo multidisciplinario experimentado. Consulte Video Resumen en http://links.lww.com/DCR/B688.