Patterns Of Relapse Research Articles

Determining Patterns of Relapse Following Pelvic Exenteration for Centrally Recurrent Gynecological Cancer: The Feasibility of Postoperative Stereotactic Radiotherapy

Determining Patterns of Relapse Following Pelvic Exenteration for Centrally Recurrent Gynecological Cancer: The Feasibility of Postoperative Stereotactic Radiotherapy

Patterns of disease-modifying therapy utilization before, during, and after pregnancy and postpartum relapses in women with multiple sclerosis

BackgroundPregnancy is a common consideration for people with multiple sclerosis (pwMS); MS onset is typically between 20 and 45 years of age, during potential child-bearing years. Pregnancy and postpartum care are a significant factor influencing disease-modifying therapy (DMT) selection for many pwMS. To date, few DMTs are considered safe to continue during pregnancy and real-world treatment patterns before, during, and after pregnancy remain uncharacterized. Evolving guidance is needed regarding how to optimize management of the pregnancy and postpartum periods considering the changing DMT landscape. This analysis in two large claims databases describes DMT utilization for the treatment of MS before, during, and after pregnancy and relapse patterns during pregnancy and postpartum. MethodsIn this retrospective, observational study, the US MarketScan Commercial and Medicaid claims database was assessed for female patients aged 18–55 years with ≥1 insurance claim submitted under the diagnosis code of MS from 01 January 2016–30 April 2021 and continuous enrollment eligibility from ≥6 months prior to pregnancy date (preconception) through 6 months of follow-up following delivery (postpartum period). Comorbid conditions were examined preconception and postpartum, including anxiety and depression. Moderate/severe relapse was defined as MS-related hospitalization, or an outpatient visit and one claim within 7 days of the visit with steroids or total plasma exchange. ResultsA total of 944 patients (mean [standard deviation] age, 32.4 [5.0] years) were eligible; 688 (73%) were commercially insured and 256 (27%) received Medicaid. Compared with commercially-insured patients, use of DMTs was lower among Medicaid patients at 6 months preconception (25.4% vs 40.4%; p < 0.001), with similar patterns observed both during pregnancy and postpartum. Overall, prevalence of DMT use declined sharply during pregnancy, from 36.3% of patients in the 6 months preconception to 17.9%, 5.3%, and 5.8% in trimesters 1, 2 and 3, respectively. Postpartum DMT utilization increased to 20.9% at 0–3 months and 24.4% at 4–6 months. Of all patients in the preconception period, the most frequently used DMTs were glatiramer acetate (14.3%), dimethyl fumarate (6.0%), interferon (5.2%), and natalizumab (4.9%). Due to small sample size, information was limited for anti-CD20s and alemtuzumab. The proportion of patients with any moderate/severe relapse declined over pregnancy (preconception, n = 82 [8.7%]; pregnancy, n = 25 [2.6%]), but increased postpartum (n = 94 [10.0%]). Of the 889 patients who stopped DMT during pregnancy, the risk of postpartum relapses was lower in the patients who resumed DMT postpartum (10/192) than in patients who did not (76/697) (5.2% vs 10.9%; odds ratio, 0.455 [95% confidence interval 0.216–0.860], p = 0.018). Cases of postpartum depression and anxiety were significantly lower in commercially-insured patients vs Medicaid patients (postpartum depression, 13.7% vs 27.0%, p < 0.01; postpartum anxiety, 16.3% vs 30.5%, p < 0.01). ConclusionDMT utilization declined sharply during pregnancy; it gradually increased postpartum but remained below pre-pregnancy use. The proportion of pwMS experiencing a moderate/severe relapse and number of relapses declined over pregnancy but increased postpartum. Reinitiation of DMT during the postpartum period was associated with lower risk of relapses, supporting a role for early reinitiation of DMT postpartum. Study supported byBiogen

MDB-69. RADIOLOGICAL PATTERNS OF RECURRENCE IN MEDULLOBLASTOMA SUBGROUPS AND CORRELATION WITH SURVIVAL

Abstract BACKGROUND Medulloblastomas can recur in up to one-third of the patients despite optimal therapy. The knowledge of the molecular group can provide clues to the possible pattern of relapse and the course of disease, with therapeutic implications. In the present study, we have identified anatomical locations and radiological patterns of relapse. METHODS AND MATERIALS Patients with a histopathological diagnosis and available subgroups of medulloblastoma with first relapse, treated in a single tertiary care center during 2005-2021 with available magnetic resonance imaging of brain and spine were included in the retrospective study. Statistical analysis was done using Pearson chi-square test and Fisher’s exact test. RESULTS 127 patients were included in the final analysis. Median age at diagnosis was 12 years and time to first recurrence was 21 months. Tumor bed relapse was seen in 49% cases, maximum in SHH subgroup, p&amp;lt;0.01. Involvement of the ventricular system (including cisterns and ventricles) was seen in 37% of cases, and was significantly associated (p:&amp;lt;0.01) with non-WNT, non-SHH tumours. Leptomeningeal metastasis was seen in 36% of cases, with significant association (p&amp;lt;0.01) in group 3 (75% of all group 3 cases) and group 4 tumors (50% of all group 4 cases). Disease in spine was most common in group 3 (65%) and group 4 tumours (71%), p&amp;lt;0.01. Hippocampus was involved in 19 cases (15%), mostly in non-WNT, non-SHH (14 cases). Significant difference in survival after recurrence was seen with ventricular, extraventricular metastases with one year survival 83% and 73% respectively, p=0.02. Hippocampal involvement showed significantly decreased survival, one year survival of 37%, p&amp;lt;0.01. CONCLUSIONS Leptomeningeal dissemination and diffuse disease were mostly seen in group 3 tumours, indicating their aggressive nature. The lower rates of ventricular relapse and around hippocampus in SHH medulloblastoma provide the opportunity to explore hippocampal avoidance-craniospinal irradiation.

GCT-08. THE PURSUIT OF OPTIMUM TREATMENT FOR NONGERMINOMATOUS GERM CELL TUMOURS (NGGCT) OF THE CNS – A PROGRESS REPORT FROM THE EUROPEAN GROUP (SIOP CNS GCT II)

Abstract BACKGROUND Controversy surrounds the optimum treatment for localised nongerminomatous germ-cell-tumours (NGGCT). The European group has employed more dose-intense chemotherapy followed by 54 Gy focal radiotherapy (fRT), whilst others additionally apply whole-ventricular or craniospinal radiotherapy (CSI). Historically, these approaches have led to comparable outcomes. PATIENTS/METHODS SIOP-CNS-GCT-II aimed to improve event free survival (EFS) for NGGCT by standardising the surgical approach for residual disease and by chemotherapy dose escalation in patients identified as high-risk (age &amp;lt;6 years and/or serum/CSF AFP &amp;gt;1000 ng/ml). Standard treatment with four courses of cisplatin, etoposide and ifosfamide (PEI) followed by 54 Gy fRT with 30 Gy CSI for metastatic disease, was retained from the SIOP-CNS-GCT-96 trial for patients not defined as high-risk. Radiotherapy technique (protons or photons) was not dictated in the trial, but the number of cases receiving proton beam therapy has increased over time. Between 02/2012 and 07/2018, 112 patients with NGGCT from eight European countries were treated according to the SIOP-CNS-GCT-II protocol; 89 were standard-risk, and 14 of these were metastatic. This compared with 149 NGGCT patients treated overall in SIOP-CNS-GCT-96, of which 33 were metastatic. RESULTS In SIOP-CNS-GCT-96, 3-year EFS for localised NGGCT receiving PEI chemotherapy and 54 Gy fRT was 0.72, and for metastatic cases, receiving PEI and 30 Gy CSI with boost, 0.68. In SIOP-CNS-GCT-II, 3-year EFS for metastatic cases receiving similar treatment was excellent at 0.94 (p=0.087 compared with SIOP-CNS-GCT-96) but for localised cases, only 0.63 (p=0.032). CONCLUSION To understand the impact of radiotherapy volumes on EFS and guide future trials, a detailed dosimetric study on the patterns of relapses is in progress. In the meantime, based on our current understanding, most participating countries are recommending addition of whole ventricular radiotherapy to fRT for localised NGGCT.

EPEN-01. DISTINCT RELAPSE PATTERN ACROSS MOLECULAR EPENDYMOMA TYPES

Abstract BACKGROUND Ependymoma (EPN) is not a uniform disease but represents different tumor types with biological and clinical heterogeneity. Some types have an excellent prognosis; others display frequent relapse. However, the pattern of when and where different types of EPN relapse is largely unknown. METHODS We assembled 552 intracranial EPN from pediatric (n=445) and adult (n=107) patients from European and Northern American cohorts and correlated DNA methylation patterns and copy-number alterations with clinical information. Median age at diagnosis was 13.4±18.8 (0.1 – 80) years. RESULTS In 271/552 (49.1%) of included EPN relapse occurred. First relapses occurred in the initial tumor bed in 70.9%, 22.4% were metastatic only, and 6.7% were combined local and metastatic. First relapses of PF-EPN-B (PF: posterior-fossa) and PF-EPN-SE (SE: subependymoma) occurred later than of PF-EPN-A, ST-EPN-YAP (ST: supratentorial), or ST-EPN-ZFTA (median time to relapse: 4.3 and 6.0 years vs. 1.9/1.0/2.5 years; p&amp;lt;0.01). Metastatic or combined recurrences in PF-EPN-B and -A occurred more often in the spinal cord than in ST-EPN-ZFTA (75.0% and 40.0% vs. 12.5%; p&amp;lt;0.01). In the latter, relapse occurred more frequently when harboring an alternative fusion or CDNK2A loss (p&amp;lt;0.01, respectively). No distant relapses were observed in ST-EPN-YAP (n=9) or PF-EPN-SE (n=60). Post-relapse survival (PRS) was poor for PF-EPN-A and ST-EPN-ZFTA (5-year PRS: 44.5±4.4/ 47.8±9.1%), whereas PF-EPN-B and PF-EPN-SE displayed a 5-year PRS of 89.5±7.1/ 90.0±9.5% (p=0.03). However, 10-year PRS for PF-EPN-B dropped to 45.8±17.3%. CONCLUSIONS Relapse patterns of specific EPN types are different. Duration of surveillance and diagnostics should be planned incorporating entity-specific relapse information. Follow-up should be performed longer than 5 years after diagnosis. Spinal MRI should be considered as standard procedure during surveillance, particularly for PF-EPN-A, PF-EPN-B and ST-EPN-ZFTA.

SBRT in Lymph-Nodal Oligometastases from Prostate Cancer: Different Outcomes between Pelvic and Para-Aortic Disease.

Background: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph nodes; instead, para-aortic lymph nodes are considered as distant metastases. The aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Methods: This is a retrospective analysis. De novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; the pattern of recurrence was also evaluated. A propensity score matching (PSM) was applied to create comparable cohorts. The primary end-point was the progression-free survival (PFS). The secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS), and pattern of relapse. Results: In total, 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. The median PFS was 20 and 11 months in pelvic and para-aortic patients, respectively (p = 0.042). The difference was not confirmed in the multivariate analysis (p = 0.06). The median BRFS was 16 and 9 months, respectively, in the pelvic and para-aortic group (p = 0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-year LPFS was 90.5%. In PSM, no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have a PFS comparable to pelvic disease; local control is high in both cohorts. Our results also support the use of SBRT for para-aortic metastases.

Patterns of recurrence after esophagectomy following neoadjuvant Immunochemotherapy for esophageal squamous cell carcinoma.

e16101 Background: To explore the recurrence pattern and risk factors of the initial relapse for esophageal squamous cell carcinoma (ESCC) who received radical surgery following neoadjuvant Immunochemotherapy (NICT). Methods: We reviewed 191 ESCC patients who underwent radical surgery following NICT from 2020 to 2022. The pattern of the first postoperative failure and simple lymph node (LN) recurrence were analyzed. Risk factors for failure were analyzed using logistic multivariate regression. Postoperative recurrence-free survival (RFS) was determined using the Kaplan-Meier method, and the log-rank test was applied to assess differences. Results: Until November 26, 2023, 66 of 191 patients experienced postoperative failure. The failure rates at 6 months, 1 year and 2 years were 7.3%, 21.0% and 37.4%, respectively. The overall recurrence pattern included single-pattern recurrence (84.8%) and multiple-pattern recurrence (15.2%). Among the single-pattern recurrence, simple LN recurrence (77%) was the most common. In total, 112 recurrent areas were observed in 43 patients with simple LN recurrence, and the failure rates of cervical, mediastinal and abdominal LNs were 15%, 70% and 15%, respectively. In patients with mediastinal LN failure, superior mediastinal LN recurrence accounted for the highest proportion (54%,60/112), of which 2R (16%,18/112) and 4R (14%,16/112) were the most frequent. The highest proportion (71.4%) of LN failure was located outside the scope of surgical dissection, and the highest incidence was in the supraclavicular area (21%) and the mediastinal 4R area (20%). According to the number of dissected LN areas, patients were divided into three groups: 1-6≤, 6-9≤, and 9-14≤. The 2-year RFS rates for three groups were 50.5%, 72.3%, and 63.5%, respectively (P = 0.04). According to the number of dissected LNs, patients were divided into three groups: 15 &lt; , 15-30 &lt; , and ≥30. The 2-year RFS rates of the three groups were 49.7%, 61.6%, and 71.6%, respectively (P = 0.28). Subgroup analysis showed that the 2-year RFS rates in ypT0-1N0 patients were 80%, 90% and 78.4% (P = 0.56), respectively, and ypT0-1N0 patients with more than 30 LNs did not show significant advantage. Multivariate analysis showed that tumor length &gt; 5 cm, preoperative efficacy evaluation of stable disease (SD), number of dissected LN areas≤6, and ypN2-3 stage were unfavorable factors for postoperative failure in patients. Conclusions: LN recurrence is a common failure mode after radical surgery following NICT for ESCC, and the LN recurrence in the mediastinal 4R and 2R regions is the most common. Tumor length &gt; 5cm, preoperative efficacy evaluation of SD, number of dissected LN areas≤6, and ypN2-3 stage were unfavorable factors for postoperative failure in patients. The suitability of extensive and multiple LN dissection after NICT in ESCC remains to be further investigated.

Combined impact of primary tumor molecular profile and location in the relapse pattern of early-stage, microsatellite stable colorectal cancer.

Combined impact of primary tumor molecular profile and location in the relapse pattern of early-stage, microsatellite stable colorectal cancer.

The patterns and risk factors for relapse in oesophageal squamous cell cancers that achieve pathological complete response to neoadjuvant chemoradiotherapy.

The goal of this study was to investigate the patterns and risk factors for recurrence in patients with oesophageal squamous cell carcinoma with a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT). Between January 2008 and December 2018, a total of 96 patients with pCR were enrolled in this study. Lymph nodes with a pCR [LN-ypCR response (+)] were defined as those lymph nodes without residual tumour but with the presence of treatment response to nCRT. Prognostic factors for recurrence-free survival (RFS) were analysed with Cox proportional hazards models and Fine-Gray competing risk models. Lymph node (LN) stations were counted according to the Japan Esophageal Society classification. The median follow-up time was 51.5 months. Recurrence occurred in 15 cases (15.6%) with a 9.9-month median time to recurrence and a 15.6-month median survival after recurrence. The majority of recurrent diseases developed within the first 2 years postoperatively. Distant recurrences were detected in 14 cases (14.6%), in which the most common recurrence sites were no.104 LN and the lung, followed by no.16 LN. The mean RFS in the whole cohort was 116.6 months. The LN-ypCR response (+) was identified as the independent prognostic factor for worse RFS in both the multivariate Cox model and the Fine-Gray competing risk model (P = 0.001 and P = 0.002, respectively). Relapse is not rare in oesophageal squamous cell carcinoma cases with pCR after nCRT. Distant recurrences, the predominant pattern of relapse, occur primarily within the first 2 years after oesophagectomy. Patients with pCR with an LN-ypCR response (+) have a higher risk for postoperative recurrence.

Assessing the applicability of the 2023 international MOGAD panel criteria in real-world clinical settings

IntroductionMyelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified demyelinating disorder with a diverse clinical spectrum. Diagnosing MOGAD traditionally relies on clinical judgment, highlighting the necessity for precise diagnostic criteria. Banwell et al. proposed criteria, aiming to refine the diagnostic spectrum. This study evaluates these criteria in a real-life cohort, comparing their performance with clinical judgment and describe the cohort of MOGAD patients.MethodsThis retrospective study, conducted at Hadassah Medical Center, included 88 patients with MOG-IgG antibodies. Patients with a positive or borderline MOG-IgG antibodies by cell-based assay were included. Demographics, clinical and MRI data were recorded. Cases were divided into definite MOGAD and Non-MOGAD groups as determined by the treating physician. We assessed the sensitivity and specificity of the new criteria in comparison to treating physicians’ evaluations. Additionally, we examined clinical differences between the MOGAD and Non-MOGAD groups.ResultsWe observed a strong concordance (98%) between the new MOGAD criteria and treating physicians' diagnoses. Clinical disparities between MOGAD and Non-MOGAD groups included lower EDSS scores, normal MRI scans, preserved brain volume, negative OCB results, and distinct relapse patterns. Also, compared to relapsing patients, monophasic MOGAD patients have greater brain volume and a lower age at onset.ConclusionThe study demonstrates robust accuracy of new MOGAD criteria, emphasizing their potential to enhance diagnostic precision. Treatment response integration into the MOGAD diagnosis is crucial, as it could aid in distinguishing MOGAD from other demyelinating disorders. Distinct clinical profiles highlight the importance of informed decisions in managing MOGAD and similar disorders.

Anti-Idiotypic VHHs and VHH-CAR-T Cells to Tackle Multiple Myeloma: Different Applications Call for Different Antigen-Binding Moieties.

CAR-T cell therapy is at the forefront of next-generation multiple myeloma (MM) management, with two B-cell maturation antigen (BCMA)-targeted products recently approved. However, these products are incapable of breaking the infamous pattern of patient relapse. Two contributing factors are the use of BCMA as a target molecule and the artificial scFv format that is responsible for antigen recognition. Tackling both points of improvement in the present study, we used previously characterized VHHs that specifically target the idiotype of murine 5T33 MM cells. This idiotype represents one of the most promising yet challenging MM target antigens, as it is highly cancer- but also patient-specific. These VHHs were incorporated into VHH-based CAR modules, the format of which has advantages compared to scFv-based CARs. This allowed a side-by-side comparison of the influence of the targeting domain on T cell activation. Surprisingly, VHHs previously selected as lead compounds for targeted MM radiotherapy are not the best (CAR-) T cell activators. Moreover, the majority of the evaluated VHHs are incapable of inducing any T cell activation. As such, we highlight the importance of specific VHH selection, depending on its intended use, and thereby raise an important shortcoming of current common CAR development approaches.

1083: Oligometastatic prostate cancer: different pattern of relapse between pelvic and para-aortic disease

1083: Oligometastatic prostate cancer: different pattern of relapse between pelvic and para-aortic disease

1931: Local relapse patterns after MR-assisted salvage HDR prostate brachytherapy: a prospective study

1931: Local relapse patterns after MR-assisted salvage HDR prostate brachytherapy: a prospective study

Management of post-autologous transplant relapse in patients with T-cell lymphomas.

Autologous hematopoietic cell transplantation (AHCT) is often used as a consolidation for patients with peripheral T-cell lymphomas (PTCLs) due to the poor prognosis associated with this heterogenous group of disorders. However, a significant number of patients will experience post-AHCT disease relapse. Here, we report a retrospective study of consecutive 124 patients with PTCLs who underwent AHCT from 2008 to 2020. With a median follow-up of 6.01 years following AHCT, 49 patients (40%) experienced disease relapse. As expected, more patients who were not in first complete remission experienced post-AHCT relapse. Following relapse, majority of the patients (70%) receiving systemic therapies intended as bridging to curative allogeneic HCT. However, only 18 (53%) patients eventually underwent allogeneic HCT. The estimated 3-year OS among patients proceeding to allogeneic HCT was 72% (95% CI 46%-87%). Our report details the pattern of post-AHCT relapse and the management of relapsed disease using different therapeutic modalities.

Radiation Therapy With or Without Cisplatin for Local Recurrences of Endometrial Cancer: Results From an NRG Oncology/GOG Prospective Randomized Multicenter Clinical Trial.

Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression. Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.

Convergent epigenetic evolution drives relapse in acute myeloid leukemia.

Relapse of acute myeloid leukemia (AML) is highly aggressive and often treatment refractory. We analyzed previously published AML relapse cohorts and found that 40% of relapses occur without changes in driver mutations, suggesting that non-genetic mechanisms drive relapse in a large proportion of cases. We therefore characterized epigenetic patterns of AML relapse using 26 matched diagnosis-relapse samples with ATAC-seq. This analysis identified a relapse-specific chromatin accessibility signature for mutationally stable AML, suggesting that AML undergoes epigenetic evolution at relapse independent of mutational changes. Analysis of leukemia stem cell (LSC) chromatin changes at relapse indicated that this leukemic compartment underwent significantly less epigenetic evolution than non-LSCs, while epigenetic changes in non-LSCs reflected overall evolution of the bulk leukemia. Finally, we used single-cell ATAC-seq paired with mitochondrial sequencing (mtscATAC) to map clones from diagnosis into relapse along with their epigenetic features. We found that distinct mitochondrially-defined clones exhibit more similar chromatin accessibility at relapse relative to diagnosis, demonstrating convergent epigenetic evolution in relapsed AML. These results demonstrate that epigenetic evolution is a feature of relapsed AML and that convergent epigenetic evolution can occur following treatment with induction chemotherapy.

Reconstructive flap surgery in head and neck cancer patients: an interdisciplinary view of the challenges encountered by radiation oncologists in postoperative radiotherapy.

Major advances have been made in reconstructive surgery in the last decades to reduce morbidity in head and neck cancer. Flaps are now present in 80% of patients with oral cavity cancer to cover anatomic, functional, and cosmetic needs. However, gaps in interdisciplinary innovation transfer from surgery to postoperative radiotherapy (poRT) remain challenging. We aimed to provide an interdisciplinary view of the challenges encountered by radiation oncologists in planning head and neck postoperative radiotherapy. A systematic and critical review was conducted to address areas of optimization in surgery and radiology that may be relevant to poRT. Despite extensive surgical literature on flap techniques and salvage surgery, 13 retrospective series were identified, where flap outcomes were indirectly compared between surgery alone or poRT. These low-evidence studies suggest that radiotherapy accelerates flap atrophy, fibrosis, and osteoradionecrosis and deteriorates functional outcomes. Preliminary evidence suggests that tumor spread occurs at the flap-tissue junction rather than in the flaps. One prospective 15-patient study showed 31.3% vs. 39.2% flap volume reduction without or with poRT. In an international consensus, experts recognized the needs for optimized flap-sparing poRT against flap-related functional deterioration and bone damage. CT, MRI, and PET-CT modalities show potential for the delineation of the junction area between native tissues and flap for flap segmentation and to characterize flap-specific changes quantitatively and correlate them with patterns of relapse or complications. Flap management in poRT is insufficiently documented, but poRT seems to damage flaps. Current gaps in knowledge underscore the need for prospective flap assessment and interdisciplinary trials investigating flap morbidity minimization by flap-sparing poRT planning.

Anatomical assessment of local recurrence site in breast cancer patients after breast reconstruction and post-mastectomy radiotherapy: implications for radiation volumes and techniques.

Post-mastectomy radiotherapy (PMRT) improves local control rates and survival in patients with adverse prognostic features. The dose coverage to target volumes is critical to yield maximum benefit to treated patients, increasing local control and reducing risk of toxicity. This study aims to assess patterns of breast cancer relapse in patients treated with mastectomy, breast reconstruction and PMRT. Breast cancer patients treated with PMRT between 1992 and 2017 were retrospectively reviewed. Clinical and pathological characteristics of patients were collected. Recurrences were defined as "in field," "marginal" or "out of field." Survival analyses were performed in relation to progression-free survival (PFS) and overall survival (OS). Correlation between baseline features was explored. Data of 140 patients are collected. After a median follow-up time of 72 months, median PFS and OS of 63 and 74 months were detected, respectively. Neoadjuvant chemotherapy, lympho-vascular space invasion (LVI) and size of primary tumor were all significantly associated with worst PFS and OS. Ten patients developed local recurrence: 30% "in field," 30% marginal recurrences, 20% "out of field" and 20% both "in field" and "out of field." No recurrence was detected under the expander, 80% above the device and 20% patients relapsed on IMN chain. The mean distant relapse-free survival was 39 months. Overall, 39 of 140 patients developed distant metastases. The onset of local-regional relapses occurred mainly above the expander/prosthesis, underlying the importance of inclusion of the subcutaneous tissues within the target volume. In order to refine new contouring recommendations for PMRT and breast reconstruction, future prospective studies are needed.

Patterns of Failure After Prostate-Only Radiotherapy in High-Risk Prostate Cancer: Implications for Refining Pelvic Nodal Contouring Guidelines

PurposeTo study prostate specific membrane antigen – positron emission tomography (Ga68PSMA-PETCT) based patterns of relapse at biochemical failure (BCF) after prostate-only radiotherapy (PORT) in high-risk (HR) prostate cancer and its implications on pelvic contouring recommendations. Methods and materialsPatients with clinico-radiological high-risk node-negative prostate cancer treated with curative PORT and androgen deprivation therapy (ADT), either within the POP-RT randomised trial or off trial, who underwent a Ga68PSMA-PETCT upon BCF were included. Patterns of regional and distant recurrence on Ga68PSMA-PETCT were studied. Pelvic nodal recurrences were mapped with reference to the superior border of pubic symphysis. Pelvic lymph nodal caudal border (PLNcb) recommendations in the published contouring guidelines (RTOGcb, GETUGcb, PIVOTALcb, NRGcb, GFRUcb) were evaluated. ResultsOf the total 262 patients screened, 68 eligible patients were included (POP-RT trial 35 patients; off-trial 33 patients). Median follow-up was 91 months (IQR, 72–117) and median time to BCF was 65 months (IQR, 49–83). Regional and distant recurrence was seen in 31 (46%) and 31 (46%) patients, respectively. Of the nodal recurrences, nearly half (46%, 14/31) had no distant metastases and 64% (20/31) had a failure in the common iliac nodal region. The lower-most nodal recurrence was 20 mm cranial to the top of pubic symphysis (RTOGcb, GETUGcb, GFRUcb) and 10 mm cranial to the PIVOTALcb. The PLNcb recommended by NRG guideline (NRGcb) had an inter-patient variability of 32 mm, ranging from 16 mm above to 16 mm below the top of pubic symphysis, and the lower most nodal recurrence ranged from 4 mm to 36 mm cranial to NRGcb. ConclusionPelvic failures accounted for a major proportion of recurrences after prostate-only radiotherapy, with the caudal most nodal recurrence being 20 mm cranial to the top of pubic symphysis. This could have implications in defining the caudal border of contouring recommendations.

Unlocking the potential of virtual reality to expand treatment frontiers for bulimia nervosa: a pilot study to explore the impact of virtual reality-enhanced cognitive-behavioral therapy

The primary objective of this study is to assess the efficacy of a Virtual Reality (VR) intervention when compared to an integrated multimodal medically managed Inpatient Program (IP) in a cohort of 24 female patients diagnosed with Bulimia Nervosa (BN). Psychological measures (i.e., EDI-2) were assessed at three points: pre-treatment, post-treatment, and at 1-month follow-up. Behavioral measures (i.e., BMI) were evaluated at 6 different time points, instead (i.e., pre-treatment, post-treatment, 3, 6, 9, and 12 months from the discharge date). The VR treatment was more effective in improving the EDI subscales EDI-DT (i.e., drive for thinness) and EDI-BU (i.e., binging-purging behaviors). In particular, patients in the VR condition showed a reduced EDI-BU score at 1-month follow-up and post-test in comparison to the pre-test, as well as a lower EDI-DT score at 1-month follow-up compared to the pre-test. Conversely, no significant changes were noted in the IP group for either subscale. Regarding the behavioral measures, the group undergoing the VR condition reported the maintenance of the BMI in the long term compared to the IP. Specifically, in the VR group BMI decreased from the pre- to post-test, and from the pre-test to the 12-month follow-up. In the IP group, BMI improved from the pre- to the post-test, and from the pre-test to the 12-month follow-up. However, a relapse pattern was observed in the IP condition during the follow-up period, with a significant BMI increase from the post-test to the 9-month follow-up, from the 3 to the 9-month follow-up, from the 6 to the 9-month follow-up, and a decrease of BMI between the 9 and the 12-month follow-up. In conclusion, these results suggest that integrating VR treatment into the care of individuals with BN could enhance both immediate and sustained treatment outcomes. This may offer valuable insights for future studies to expand and delve deeper into the field of EDs.