Neoadjuvant Radiotherapy Research Articles

The Evolving Role of Neoadjuvant Radiation Therapy in Pancreatic Adenocarcinoma

Background/Objectives: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Surgical resection is the most reliable chance for cure, but high rates of positive margins and local failure persist. Neoadjuvant therapies (NAT), including chemotherapy and radiation therapy (RT), are being explored to improve surgical outcomes, particularly in borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). This review aims to summarize the current landscape and future directions for neoadjuvant RT (NART) in PDAC. Methods: The review includes a detailed analysis of past and ongoing clinical trials investigating various NART approaches in PDAC, with an emphasis on different RT techniques, fractionation schemes, and their integration into multimodal treatment strategies. Results: Early evidence suggests that NART can improve resection margins and local control. However, recent trials, including the Alliance A021501 and LAP-07 trials, have failed to demonstrate significant survival benefits with the addition of RT to NAT. Nevertheless, nuances in trial design and execution continue to keep the question of NART open. Newer approaches, such as stereotactic magnetic resonance-guided adaptive radiation therapy (SMART), show promise in improving local control and survival, but further phase 3 trials are needed. Conclusions: While NART has shown potential in improving local control in PDAC, its impact on overall survival remains unclear. Ongoing trials, particularly those utilizing advanced techniques like SMART, are critical in defining the role of RT in the neoadjuvant setting for PDAC. Collaboration across multidisciplinary teams is essential to optimize treatment strategies and trial outcomes.

The diagnosis and oncological outcomes of obturator and internal iliac lymph node metastasis in middle–low rectal cancer: results of a multicenter Lateral Node Collaborative Group study in China

BackgroundLateral lymph node dissection (LLND) can decrease local recurrence to lateral compartments in middle-low rectal cancer, but pathological evidence for optimal surgical indications, especially after neoadjuvant (chemo)radiotherapy (nCRT), is lacking. This study aimed to identify the predictive factors and oncological outcomes for different LLN locations associated with pathological metastasis.MethodIn this multicenter study, patients from 19 centers who underwent total mesorectal excision (TME) with LLND for locally advanced mid-/low rectal cancer from January 2012 to December 2021 were included.ResultsAll 566 included patients underwent TME with LLND surgery; 241 (37.4%) of the largest LLNs were located in the obturator area, and 403 (62.6%) of the largest LLNs were located in the internal iliac area. Multivariate analysis revealed that a short-axis size of 9 mm for the obturator area and 6 mm for internal iliac nodes constituted a reliable indicator of pathological LLN metastasis in non-CRT patients. In nCRT patients, a short-axis node size of 7 mm for obturator nodes and 4 mm for internal iliac nodes could be used to accurately predict pathological LLN metastasis. In contrast to pathological internal iliac node metastasis, pathological obturator node metastasis was associated with lower distant metastasis-free survival (DMFS) (P = 0.001), cancer-specific survival (CSS) (P = 0.043), and overall survival (OS) (P = 0.009), but lower lateral local recurrence-free survival (LRFS) (P > 0.05) was not statistically significant.ConclusionsThe obturator and internal iliac nodes may be two completely different types of LLNs, and the optimal cutoff value for predicting pathological LLN metastasis is inconsistent regardless of nCRT.Clinical trial registration The protocol of the current study was registered on ClinicalTrials.gov (NCT04850027), and the protocols were in accordance with the standards set by the World Medical Association Declaration of Helsinki.

Effects of Neoadjuvant Radiation and Recipient Vessel Characteristics on Microvascular Complication Rates in Reconstruction of Lower Extremity Soft-Tissue Sarcoma Defects.

The treatment approach for soft-tissue sarcomas (STS) of the lower extremity has shifted toward the use of neoadjuvant radiation combined with limb-sparing surgery (LSS). The resulting defects often require reconstruction with free tissue transfer for adequate outcomes. Data has demonstrated a potential increased risk of microvascular complications for free flaps performed using irradiated recipient vessels. Similarly, certain anatomic areas of the lower extremity have a high proportion of unnamed perforators that are available as recipient vessels, increasing the technical difficulty. We aimed to determine if the characteristics of recipient vessels that were used for reconstruction of STS defects influenced rates of microvascular complications in our patients. A retrospective chart review of all patients who underwent reconstruction of lower extremity STS defects with free tissue transfer from 2009-2020 was conducted. Data regarding recipient vessel type (axial vessel vs. unnamed perforator), radiation status of the recipient vessels (irradiated vs. non-irradiated), and microvascular complications was compared across groups. A total of 204 free flaps were included. The overall microvascular complication rate was 13.7% (28 cases). Most microvascular complications were detected postoperatively (82.1%) rather than intraoperatively, with the majority involving venous congestion/thrombosis (20 cases, 71.4%). While there was a trend toward increased microvascular complications with the use of irradiated recipient vessels (27 cases, 96.4%), this did not reach statistical significance (OR = 1.98, p = 0.52). The use of perforating branches as recipient vessels did not confer increased risk of microvascular complications (OR = 0.87, p = 0.75). Reconstruction of irradiated lower extremity STS defects represents a particularly challenging issue. This analysis demonstrates that free tissue transfer can be safely performed using irradiated vessels without significant increased risk of microvascular complications. Furthermore, unnamed perforating branches can also be successfully used for reconstruction in anatomically challenging areas of the lower extremity.

Predictive Value of GINI and ALBI Grades in Esophageal Cancer Receiving Chemoradiotherapy

Objectives: The principal objective of this study was to assess the predictive efficacy of the global immune–nutrition–inflammation index (GINI) and the albumin–bilirubin (ALBI) score among patients receiving chemoradiotherapy for esophageal cancer. Methods: A retrospective analysis was conducted on 46 patients who received definitive or neoadjuvant radiotherapy for esophageal cancer at our institution. Blood samples were collected from these patients prior to the initiation of radiotherapy to measure the biomarkers, including the C-reactive protein (CRP), neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR), the global immune–nutrition–inflammation index (GINI), and the albumin–bilirubin (ALBI) grade. The predictive significance of these biomarkers for progression-free survival (PFS) and overall survival (OS) was evaluated using both univariate and multivariate Cox regression analyses. Results: The median follow-up time for this study was 19.5 months (range: 2.6–166.3 months). Univariate analysis revealed that the platelet count (p = 0.003) and monocyte count (p = 0.04) were significant predictors of PFS. In the multivariate analysis, only the platelet count (p = 0.005) remained an independent predictor of PFS. Univariate analysis demonstrated that the neutrophil count (p = 0.04), lymphocyte count (p = 0.01), NLR (p = 0.005), PLR (p = 0.004), CRP (p = 0.02), ALBI grade (p = 0.01), and GINI (p = 0.005) were significant predictors of OS. Multivariate analysis identified the GINI as a predictor of OS, approaching statistical significance (p = 0.08). Conclusion: The results of our study indicate that the pretreatment GINI and ALBI grades are significantly and independently associated with the OS rates in patients with esophageal cancer who are undergoing chemoradiotherapy.

Treatment patterns and outcomes of locally advanced endometrial cancer patients treated with neoadjuvant radiation

Treatment patterns and outcomes of locally advanced endometrial cancer patients treated with neoadjuvant radiation

One-Stage Surgical Resection and Functional Reconstruction for Upper Limb Soft Tissue Sarcoma.

Currently, the gold standard of treatment for extremity soft tissue sarcoma (STS) is limb-sparing surgery. When the upper extremity is involved, the functional outcome is frequently poor. A 1-step resection and functional reconstruction would be advisable to obtain a fast recovery. Our study aims at retrospectively analyzing our case series of immediate nerves and tendons reconstructions of the upper limb after STS resection, while combining a review of the literature. A retrospective review was conducted on a consecutive series of patients who underwent an immediate functional reconstruction after STS resection of the upper limb between 2015 and 2022 among the IRCCS Foundation "Istituto Nazionale dei Tumori." The Disabilities of the Arm, Shoulder and Hand (DASH) score was considered the primary outcome. The obtained DASH scores were compared through groups that underwent different reconstructive procedures. The literature review was conducted according to the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) criteria among 3 databases (PubMed, EMBASE, and Cochrane) using the search parameters "(((upper extremity) OR (upper limb)) AND (functional reconstruction) AND (soft tissue sarcoma)." Between 2015 and 2022, 52 patients required a functional reconstruction. The mean follow-up time was 49.63 months. The DASH score analysis reported a mean value of 44.1 ± 26.7. A statistically significant difference was found between groups who underwent different reconstruction techniques, whereas no difference was found regarding exposure to neoadjuvant radiation therapy. The literature review reported few articles focusing on immediate functional reconstruction after STS resection, and only 6 articles were included in the review. Our review aimed at reporting our case series of immediate functional reconstructions after STS of the upper extremity, which is currently the most substantial one reported in literature to set an effective baseline for further studies in the field.

Safety and Efficacy of Neoadjuvant Docetaxel and Radiotherapy in Localized High-Risk Prostate Cancer: Results From a Prospective Pilot Study.

Approximately 15% of patients with localized prostate cancer are at high risk for disease recurrence. Many clinical trials have evaluated the impact of neoadjuvant therapy before radical prostatectomy with mixed results (NCT00321698). This phase I/II clinical trial evaluated the tolerability and preliminary efficacy of neoadjuvant radiation therapy and docetaxel before prostatectomy in 25 men with high-risk prostate cancer. The treatment regimen included 45Gy radiotherapy in 25 fractions to the prostate and seminal vesicles over 5 weeks, along with weekly dose-escalated docetaxel up to 30mg/m², followed by prostatectomy and bilateral lymph node dissection. The primary endpoint was the rate of pathologic complete response (pCR). Secondary endpoints included adverse events, symptom and quality of life measures, and prostate-specific antigen metrics. All 25 patients completed the planned treatment. The primary endpoint of pCR was not achieved. Lymphopenia was the most common grade 3 or higher toxicity, with no grade 3 or higher genitourinary or gastrointestinal toxicities observed. With a median follow-up of 11.6 years, the 10-year biochemical recurrence-free survival was 60%, and distant metastasis-free survival was 80%. Prostate cancer-specific survival and overall survival at 10 years were 84% and 60%, respectively. Although pCR was not met, the treatment demonstrated a modest toxicity profile and reasonable long-term outcomes, suggesting feasibility and safety. Further studies are needed to optimize endpoints and assess the efficacy of neoadjuvant treatments compared with standard approaches in high-risk prostate cancer patients.

Predictive factors for pathological complete response to neoadjuvant therapy in locally advanced rectal cancer: a review of current research

The guidelines advocate for preoperative neoadjuvant radiotherapy and chemotherapy in cases of middle and low locally advanced rectal cancer. While some patients achieved pathological complete response (pCR), which is favorable and allows for potential organ preservation, treatment sensitivity varies and not all patients reach pCR. Identifying the factors influencing pCR is important for enhancing the effectiveness of neoadjuvant therapy and improving patient outcomes. Previous research has identified various factors associated with response to neoadjuvant therapy, which can serve as predictors of pCR. This study reviews recent literature on imaging, pathological, genetic, and molecular characteristics, laboratory indices, and therapeutic factors related to tumor response, both domestically and internationally. The aim is to summarize the latest advancements in understanding the factors associated with pCR in patients with locally advanced middle and low rectal cancer undergoing neoadjuvant therapy, thereby providing a theoretical foundation for standardized clinical treatment approaches.

Postoperative Morbidity and Factors Predicting the Development of Lymphoceles Following Lateral Pelvic Node Dissection for Rectal Cancer: A Cohort Study.

Lateral pelvic node dissection (LPLND) is indicated inthe surgical management of clinically significant pelvic lymphadenopathy associated with rectal malignancies. However, procedure-related morbidity, including the incidence and predisposing factors for lymphoceles arising in this setting have not been adequately evaluated. This retrospective single-institution study included 183 patients with nonmetastatic, lateral node-positive rectal cancer undergoing total mesorectal excision with LPLND between June 2014 and May 2023 to determine the incidence and severity of postoperative complications using the Clavien-Dindo system, with logistic regression performed to model a relationship between lymphocele-development and potentially-predictive variables. In this cohort, mean age was 45.3 ± 12.81 years, 62.8% were male, and 27.9% had body mass index ≥ 25kg/m2. Median tumor-distance from the verge was 3.0 (interquartile range [IQR] 1.0-5.0)cm. Following radiotherapy in 86.9%, all patients underwent surgery: 30.1% had open resection and 26.2% had bilateral LPLND. Median nodal-yield was 6 (IQR 4-8) per side. Postoperatively, 45.3% developed complications, with 18% consideredclinically significant. Lymphoceles, detected in 21.3%, comprised the single-most common sequelae following LPLND, 46.2%arising within 30 days of surgery and 33.3% requiring intervention. On multivariate analyses, obesity (hazard ratio [HR] 2.496; 95% confidence interval [CI] 1.094-5.695), receipt of preoperative radiation (HR 10.026; 95% CI 1.225-82.027), open surgical approach (HR 2.779; 95% CI 1.202-6.425), and number of harvested nodes (HR 1.105; 95% CI 1.026-1.190) were significantly associated with lymphocele-development. Pelvic lymphoceles and its attendant complications represent the most commonly encountered morbidity following LPLND for rectal cancer, with obesity, neoadjuvant radiotherapy, open surgery, and higher nodal-yield predisposing to their development.

Inequalities in quality metrics for colorectal cancer surgery in older adults: A retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program registry

BackgroundWith a growing proportion of patients undergoing surgery for colorectal cancer being older adults, it is unknown whether traditional quality metrics are achieved as often compared with younger adults. This work was done with a view to understand tailoring needs of quality metrics for older adults with colorectal cancer. MethodsThis retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program registry to identify adults (≥18 years) between 2016 and 2021 who underwent elective colorectal cancer surgery for nonmetastatic cancer. older adults was defined as adults ≥65 years. The association between older adults and attainment of consensus quality metrics were evaluated using multivariable logistic regression adjusting for patient, cancer, and treatment factors. ResultsOf 46,159 patients undergoing elective colon cancer resection, 18,592 (40.3%) were older adults. Being an older adult was independently associated with a 14% reduction in odds of harvest of ≥12 nodes and 4.3 times increase in odds of 30-day mortality. Of 9,106 patients undergoing elective rectal cancer resection 5,143 (56.5%) were older adults. Being an older adult was independently associated with a 19% reduction in odds of harvest of ≥12 nodes, 2.3 times increase in odds of 30-day mortality and a 44% reduction in odds of receiving neoadjuvant radiation. Findings were robust to sensitivity analyses of alternate methods of handling missing data and alternate analytic approaches. ConclusionGiven unique needs of the older adult population, interpretation of disparities in quality metrics is challenging because of an inability to differentiate between patient factors, tailored care, or bias. Monitoring and reporting of quality metrics for older adults need to be re-evaluated with consideration to stratification, unique benchmarks, and older adult–specific quality metrics.

Comparing Black and White Patients in Treatment of Advanced Prostate Cancer and Survival in an Equal Access Health System.

Racial disparities in prostate cancer treatment and survival in the U.S. have been attributed to differences in access to care and medical insurance. We aimed to compare treatment and survival of advanced prostate cancers between White and Black men in the equal access Military Health System (MHS). We accessed the MilCanEpi database to study a cohort of non-Hispanic White and Black men diagnosed with stage III or IV prostate cancer between 1998 and 2014 in the MHS. The racial groups were compared in receiving curative treatment of radical prostatectomy (RP) only, RP with (neo)adjuvant radiation or hormone therapy, radiation only, or combination radiation and hormone therapy; and overall survival using multivariable regression models. The study included 1476 White and 531 Black men. Overall, there was no racial difference in receiving any curative treatment (AOR = 0.85, 95% CI = 0.67, 1.08 for Black vs. White). By treatment type, Black men were statistically as likely to receive RP only (AOR = 0.87, 95% CI = 0.67, 1.14), radiation only (AOR = 0.81, 95% CI = 0.49, 1.34), or combination radiation and hormone therapy (AOR = 1.12, 95% CI = 0.71, 1.78) but statistically less likely to receive RP with (neo)adjuvant treatment (AOR = 0.56, 95% CI = 0.37, 0.86) relative to no curative treatment compared to White men. The difference in RP with (neo)adjuvant treatment was also statistically significant among patients with stage III tumors, but not stage IV. Survival was similar overall (AHR = 1.12, 95% CI = 0.88, 1.42 for Black vs. White) and when evaluated by tumor stage. In the MHS, the overall likelihood to receive any treatment for advanced prostate cancers and survival was similar between races, which might result from universal health care. Racial differences in receipt of RP with (neo)adjuvant treatment, especially for patients with stage III prostate cancer, may be related to factors other than access to care and warrants further research.

Identifying Clusters of Curatively-Treated Esophageal Cancer Patients Using Patient-Reported Outcome Measures at Three Months from Discharge: A Secondary Analysis from a Longitudinal Single Center Study.

This study aims to identify meaningful clusters based on Patient-Reported Outcome Measures (PROMs) in curatively-treated esophageal cancer patients at three months post-discharge. This secondary analysis of a longitudinal single-center study included 46 esophageal cancer patients who underwent curative surgery. Patients were selected based on their completion of PROMs surveys at three months post-discharge, were aged 18 years or older, and had undergone surgical resection (esophagectomy) with or without neoadjuvant chemotherapy and/or radiotherapy. The analysis utilized t-distributed Stochastic Neighbor Embedding (t-SNE) for dimensionality reduction and hierarchical clustering to analyze PROMs data collected three months post-discharge. Clustering was performed on physical, emotional, cognitive, and social functioning variables, symptom burden, and health literacy. Three distinct clusters were identified: Cluster 1 (n = 24) with higher functioning and moderate symptoms, Cluster 2 (n = 14) with moderate functioning, higher symptoms, and lower health literacy, and Cluster 3 (n = 8) with the highest functioning, lowest symptoms, and highest health literacy. Significant differences between squamous cell carcinoma and adenocarcinoma subtypes were observed across several PROMs domains, including critical health literacy, general health status/quality of life, nausea and vomiting, and insomnia. These clusters provide an exploratory framework for tailoring post-operative interventions to enhance patient recovery, which necessitates further confirmatory investigations, including outcomes such as complications and mortality, in the analysis. This study fills a research gap by demonstrating the utility of PROMs in identifying distinct recovery patterns in esophageal cancer patients post-surgery. The findings support the use of PROMs to guide personalized post-operative care, potentially improving patient outcomes and quality of life. Further research is needed to validate these findings in larger, diverse populations.

Genetic and Molecular Heterogeneity of Synovial Sarcoma and Associated Challenges in Therapy.

Synovial sarcoma (SS) is one of the most common types of pediatric soft tissue sarcoma (STS) being far less frequent in adults. This STS type is characterized by one specific chromosomal translocation SS18-SSX and the associated changes in signaling. However, other genetic and epigenetic abnormalities in SS do not necessarily include SS18-SSX-related events, but abnormalities are more sporadic and do not correlate well with the prognosis and response to therapy. Currently, targeted therapy for synovial sarcoma includes a limited range of drugs, and surgical resection is the mainstay treatment for localized cancer with adjuvant or neoadjuvant chemotherapy and radiotherapy. Understanding the molecular characteristics of synovial sarcoma subtypes is becoming increasingly important for detecting new potential targets and developing innovative therapies. Novel approaches to treating synovial sarcoma include immune-based therapies (such as TCR-T cell therapy to NY-ESO-1, MAGE4, PRAME or using immune checkpoint inhibitors), epigenetic modifiers (HDAC inhibitors, EZH2 inhibitors, BRD disruptors), as well as novel or repurposed receptor tyrosine kinase inhibitors. In the presented review, we aimed to summarize the genetic and epigenetic landscape of SS as well as to find out the potential niches for the development of novel diagnostics and therapies.

Short-Course TNT Improves Rectal Tumor Downstaging in a Retrospective Study of the US Rectal Cancer Consortium.

The RAPIDO trial showed promising rates of pathologic complete response (pCR) after neoadjuvant short-course radiation with consolidation chemotherapy (total neoadjuvant therapy [SC TNT]) for rectal cancer. Only single-center reviews comparing tumor downstaging between SC TNT and long-course chemoradiation (LCRT) have been published in the United States. We reviewed our multi-institutional experience with both. The US Rectal Cancer Consortium database (2007-2018) including data from six high-volume rectal cancer care centers was reviewed. Patients with nonmetastatic, rectal adenocarcinoma who had neoadjuvant LCRT alone or SC TNT before excision or definitive nonoperative management were included. The primary outcome was the rate of complete response (CR), including pCR or durable (12 month) clinical complete response. Of 857 included patients, 175 (20%) received SC TNT and 682 (80%) received LCRT. The LCRT group had more low tumors (51.8% vs. 37.1%, p < 0.0001) and more clinically node-negative disease (31.8% vs. 22.3%, p < 0.0001). The CR rate was higher after SC TNT (34.1% vs. 20.3%, p = 0.0001). SC TNT was a predictor of CR (OR: 2.52, CI: 1.68-3.78). SC TNT patients completing 5-6 months of consolidation chemotherapy had a CR rate of 42.9%. There was no difference in 3-year PFS. SC TNT increases CR rate when compared to LCRT. For patients seeking nonoperative options or fewer radiation treatments, SC TRT should be preferred over LCRT alone.

What Is the Prognostic Value of the Pathologic Response after Neoadjuvant Radiotherapy in Soft Tissue Sarcoma? An Institutional Study Using the EORTC-STBSG Response Score.

Background/Objectives: The relationship between pathologic findings in soft tissue sarcoma (STS) after neoadjuvant treatment and oncological outcomes remains uncertain due to varying evaluation methods and cut-off values. This study aims to assess pathologic findings after neoadjuvant radiotherapy in STS using the EORTC-STBSG response score and evaluate its prognostic value. Methods: Clinical and outcome data from 44 patients were reviewed. Resected specimens were re-evaluated to measure viable cells, necrosis, fibrosis, and hyalinization. Local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed using Kaplan-Meier survival analysis. Cox proportional hazards regression was used for univariate and multivariate analyses to correlate outcomes with pathologic response. Results: The median percentages of viable cells, necrosis, and fibrosis/hyalinization were 20%, 11%, and 40%, respectively. A pathologic complete response (pCR), defined as ≤5% viable cells, was achieved in 25% of cases. Local recurrence occurred in 33% of cases, with a significantly higher rate of 64% after R1 resection compared to 22% after R0 resection. Distant metastases were observed in 42% of patients, primarily in the lungs. The 3-year rates for LRFS, DMFS, and OS were 65%, 54%, and 67%, respectively. A correlation between outcomes and tumor size, grade and histological subtype was observed. Classifying pathologic response by the EORTC-STBSG score failed to show an association with outcomes. Patients achieving pCR showed lower risk of LR and improved OS. Conclusions: While the EORTC-STBSG score did not show a prognostic value, resection specimens with ≤5% viable cells were linked to improved LRFS and OS.

Early Outcomes of Preoperative Short Course Radiotherapy With Simultaneous Integrated Boost and Response-adapted Chemotherapy for Advanced Rectal Cancer

Background and purposeLimited evidence exists for dose escalation in neoadjuvant short course radiotherapy (SCRT) for rectal cancer. With enhanced imaging and radiotherapy techniques over the past decades along with the valuable endpoint of pathological complete response (pCR), we believe SCRT with simultaneous integrated boost could potentially provide deeper pathological responses and improve local control. Methods and MaterialsBetween January 2020 and December 2022, locoregional-advanced rectal cancer patients that were treated with neoadjuvant SCRT with simultaneous integrated boost up to 5.5–6Gy per fraction with five daily fractions followed by response-adapted chemotherapy was retrospectively reviewed. The pCR rates, R0 resection rates, tumor downstaging, toxicities, and early pattern of recurrence are reported. ResultsAmong the 76 patients, 67 (88%) were able to undergo curative intent surgery. R0 resection was achieved in 99% (n = 66) of patients with pCR rates of 28% (n = 19). Forty-six percent (n = 31) of patients had significant pathological downstaging (ypT2N0) and 55% (n = 37) of patients had both T and N downstaging. Most common grade 3 or above radiotherapy-related side-effects were proctitis, rectal pain, and dermatitis found in 5% (n = 4), 3% (n = 2) and 3% (n = 2) of patients, respectively. Grade 3 or above surgical complications were observed in 15% (n = 10) of patients. There were no treatment-related deaths. With a median follow-up of 27 months, only 6% (n = 4) had local recurrence after surgery. ConclusionsNeoadjuvant short course radiotherapy with simultaneous boost for rectal cancer is feasible with no added toxicities. Patients who underwent surgery achieve a high R0 resection and pCR rates. Early data suggest low rates of locoregional recurrence. Further follow-up and research is needed to validate and optimize the dose, method, and schedule of dose escalation.

7426 Tamoxifen-Induced Ovarian Hyperstimulation in a Pre-Menopausal Patient with Breast Cancer History: Spontaneous Resolution with Conservative Management

Abstract Disclosure: S. Gondi: None. M. Contento: None. A. Leiter: None. Background: Tamoxifen is a selective estrogen receptor modulator (SERM) that competitively binds to estrogen receptors (ER) on tumors and inhibits the effect of estrogen, which is used in the treatment and prevention of ER-positive breast cancer. Tamoxifen therapy has been reported to increase serum estrogens and cause ovarian hyperstimulation in premenopausal women, but knowledge on how to manage these conditions is limited. Clinical Case: A 36-year-old pre-menopausal female with history of malignant neoplasm of the right breast (ER positive) who completed neoadjuvant chemotherapy, lumpectomy, and radiation, on tamoxifen for seven years presented with new-onset oligomenorrhea. Laboratory testing done by the patient’s gynecologist revealed total estrogen 2,723 pg/mL (reference range [RR] 34-501), testosterone 132 ng/dL (RR 8-60), anti-Mullerian hormone 12.7 ng/mL (RR for age 0.66-8.75), ovulation-phase follicle stimulating hormone 11.5 mIU/mL (RR 4.7-21.5) and luteinizing hormone (LH) 63.3 mIU/mL (RR 14-95.6). Further workup revealed that ovarian tumor markers alpha-fetoprotein and serum human chorionic gonadotropin and other labs including dehydroepiandrosterone sulfate, progesterone 17-OH, lactate dehydrogenase, prolactin, and thyroid stimulating hormone were normal. Transvaginal ultrasound (TVUS) showed a new 2.8 x 1.9 x 2.3 cm complex left ovarian cyst, which, along with the elevated estrogen level, was concerning for ovarian hyperstimulation. Treatment with LH-releasing hormone (LHRH) agonists, surgical consultation, and discontinuation of tamoxifen were offered as potential management strategies, but the patient opted for observation and continued tamoxifen. Two months later, estradiol was 989 pg/mL (RR 85-498), and then three months later decreased to 152 pg/mL with repeat TVUS showing resolution of the left ovarian cyst. The patient’s oligomenorrhea resolved with resumption of regular menstrual cycles. Conclusion: While it is well-known that tamoxifen causes elevated serum estrogen levels and can lead to ovarian hyperstimulation, there is limited research on the management of these side effects. Treatment strategies in past cases have included oophorectomy or medical management with LHRH agonists or gonadotropin-RH agonists. However, this case demonstrates that a tamoxifen-induced ovarian cyst and high estrogen levels can resolve on its own with continued tamoxifen treatment. Conservative management with monitoring via imaging and repeat estrogen levels may be sufficient in management of pre-menopausal women with tamoxifen-induced ovarian hyperstimulation. Presentation: 6/1/2024

Is an Electronic Nose Able to Predict Clinical Response following Neoadjuvant Treatment of Rectal Cancer? A Prospective Pilot Study.

Introduction: A watch-and-wait strategy for patients with rectal cancer who achieve a clinical complete response after neoadjuvant (chemo) radiotherapy is a valuable alternative to rectal resection. In this pilot study, we explored the use of an electronic nose to predict response to neoadjuvant therapy by analyzing breath-derived volatile organic compounds. Materials and Methods: A pilot study was performed between 2020 and 2022 on patients diagnosed with intermediate- or high-risk rectal cancer who were scheduled for neoadjuvant therapy. Breath samples were collected before and after (chemo) radiotherapy. A machine-learning model was developed to predict clinical response using curatively treated rectal cancer patients as controls. Results: For developing the machine-learning model, a total of 99 patients were included: 45 patients with rectal cancer and 54 controls. In the training set, the model successfully discriminated between patients with and without rectal cancer, with a sensitivity and specificity of 0.80 and 0.65, respectively, and an accuracy of 0.72. In the test set, the model predicted partial or (near) complete response with a sensitivity and specificity of 0.64 and 0.47, respectively, and an accuracy of 0.58. The AUC of the ROC curve was 0.63. Conclusions: The prediction model developed in this pilot study lacks the ability to accurately differentiate between partial and (near) complete responders with an electronic nose. Machine-learning studies demand a substantial number of patients and operate in a rapidly evolving field. Therefore, the prevalence of disease and duration of a study are crucial considerations for future research.

Quality of life and functional outcome of rectal cancer patients: A prospective cohort study.

In the last decade, the Netherlands has implemented various diagnostic and treatment strategies to enhance rectal cancer outcomes. This study, using data from the Prospective Dutch ColoRectal Cancer (PLCRC) cohort, investigates whether these multidisciplinary advancements have translated into improved health-related quality of life (HRQoL) and functional outcomes for the general Dutch rectal cancer population. Patients with Stage I-III rectal cancer enrolled in the PLCRC cohort were included. HRQoL and functional outcomes were assessed 1 and 2 years after diagnosis using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), EORTC QLQ Colorectal Cancer 29 and the Low Anterior Resection Syndrome score. HRQoL and functional outcomes were compared based on year of diagnosis (2014-2019). A total of 1294 patients were included. Two years after diagnosis, patients diagnosed in 2019 (n = 392) had a clinically relevant higher score on physical (8.2, 95% CI 4.1-12.3), role (13.5, 95% CI 7.3-19.7) and social functioning (5.8, 95% CI 0.3-11.2) compared to those diagnosed in 2014 (n = 65). Additionally, patients diagnosed in 2019 experienced less fatigue 2 years after diagnosis compared to those diagnosed in 2014 (-8.6, 95% CI -14.1 to -3.0). The Low Anterior Resection Syndrome score showed no differences. The findings of this study suggest that over the past decade rectal cancer patients in the Netherlands have witnessed improvements in HRQoL across various domains. Most probably, the improvement is due to a combination of implementation of population screening, a more restrictive neoadjuvant radiotherapy policy and advances in minimally invasive surgery and organ preserving treatment options.

Neoadjuvant radiotherapy and endocrine therapy for oestrogen receptor positive breast cancers: the Neo-RT feasibility study

AimsTo establish safety and feasibility of delivering neoadjuvant radiotherapy and endocrine therapy for oestrogen receptor positive breast cancers with palpable size 20mm or greater, for which radiotherapy might facilitate more conservative surgery. Materials and MethodsA single arm feasibility study was conducted. Patients received whole breast radiotherapy with or without radiotherapy to nodal areas. Dose/fractionation was 40Gy in 15 fractions over 3 weeks, with or without either simultaneous integrated boost to 48Gy, or sequential boost, to the tumour bed. This was followed by endocrine treatment for 20 weeks, then surgery. The primary endpoint of the study was proportion of patients successfully completing neo-adjuvant radiotherapy and endocrine treatment followed by breast surgery. Response and toxicity endpoints including mastectomy rate, peri/postoperative complications, and pathological response were also evaluated.The primary analysis is descriptive. The study regimen would be considered feasible if more than 70% of patients completed treatment, while it might not be considered feasible if less than 50% did so. With a one sided 5% significance level and 80% power, a maximum of 43 patients would be required to detect a rate of ≤50% vs ≥70%. Results14 patients were recruited of the planned 43. Due to slow recruitment particularly during the COVID-19 pandemic, the decision was made to stop the trial in October 2021. One registered patient was found to be ineligible before starting treatment. 13/13 patients (100%, 90% CI: 75.3%, 100%) who received any trial treatment successfully completed all trial treatments. The lower bound of the Clopper-Pearson (exact) 90% confidence interval was 79%, indicating that the primary endpoint would have been met if the planned recruitment had been achieved. 3/13 patients underwent mastectomy. 7/13 had more conservative surgery than had been planned at baseline. 4/13 patients experienced any peri/postoperative complication. The only acute radiotherapy toxicities reported were grade 1/2 dermatitis and grade 1 fatigue. Long term breast outcomes were clinician assessed as none/mild at all timepoints in 12/13 patients. All tumours showed evidence of some pathological response to treatment, but none had pathological complete response. ConclusionsThis treatment schedule is likely feasible. It is difficult to draw strong conclusions on safety/toxicity given the small numbers, but these seem in keeping with other recent reports of neoadjuvant breast radiotherapy.