Patterns Of Relapse Research Articles

Long-Term Survivors after Failure of Chimeric Antigen Receptor T Cell Therapy for Large B Cell Lymphoma: A Role for Allogeneic Hematopoietic Cell Transplantation? A German Lymphoma Alliance and German Registry for Stem Cell Transplantation Analysis

The outcome of patients with large B cell lymphoma (LBCL) who relapse or progress after CD19-directed chimeric antigen receptor T cell therapy (CAR-T) administered as salvage therapy beyond the second treatment line is poor. However, a minority of patients become long-term survivors despite CAR-T failure. The German Lymphoma Alliance (GLA) has proposed a hierarchical management algorithm for CAR-T failure in LBCL, aimed at allogeneic hematopoietic cell transplantation (alloHCT) as definite therapy in eligible patients. The purpose of this study was to investigate characteristics, relapse patterns, and management strategies in long-term survivors after CAR-T failure, with a particular focus on the feasibility and outcome of alloHCT. This was a retrospective analysis of all evaluable patients with a relapse/progression event (REL) observed in a previously reported GLA sample between November 2018 and May 2021. REL occurred in 214 of 356 patients (60%) who underwent CAR-T for LBCL in the previous GLA study. An evaluable dataset was available for 143 of these 214 patients (67%). Twenty-six of 143 patients (18%) survived 12 months or longer from REL, 109 (76%) died within the first year after REL, and 8 (6%) were alive but had not reached the 12-month landmark. Long-term survivors had more favorable pre-CAR-T features, had a longer interval between CAR-T and REL, and had more often received a tumor biopsy after CAR-T failure, whereas the choice of the first salvage regimen had no impact. AlloHCT was feasible in 40 of 53 patients (75%) intended and resulted in a 12-month post-transplantation overall survival of 36% in those patients who underwent transplantation with sensitive or untreated REL. AlloHCT after CAR-T failure in LBCL is feasible and may be an important contributor to long-term survival, although selection bias must be taken into account. Thus, alloHCT should be considered as a reasonable treatment option for eligible patients in this setting. However, because the overall outlook after CAR-T failure remains poor, novel effective therapeutic approaches are needed, either to allow long-term disease control per se or to improve the preconditions for successful alloHCT.

Patterns of recurrence in FIGO stage IB1-IB2 cervical cancer: Comparison between minimally invasive and abdominal radical hysterectomy

ObjectiveAim of our study was to evaluate whether the different laparotomic (ARH) or minimally invasive (laparoscopic and robotic) approaches (MIS) in FIGO stage IB1-IB2 cervical cancer, present different patterns of recurrence of the disease. The secondary endpoint of the study was the evaluation of the variables most involved with the risk of relapse and therefore lower DFS and OS. Material and methodsThe study enrolled patients with definitive histological diagnosis of squamous or adenocarcinoma stage IB1-IB2 cervical cancer who underwent minimally invasive or abdominal radical hysterectomy from 2001 to 2018. ResultsThe study enrolled 360 patients and 59 patients (16.4 %) reported a disease relapse. The data showed that ARH group was not associated with different recurrence patterns than MIS group (p = 0.14). Moreover, there was no statistically significant difference regarding DFS (p = 0.52) and OS (p = 0.29) between the ARH group and the MIS group. ConclusionsMIS, in FIGO stage IB1-IB2 cervical cancer, is not associated with different relapse patterns compared to ARH, nor with a higher risk of distance metastasis and finally, without significant difference in term of DFS and OS. More studies are needed to determine the factors that modify the site of relapse.

KS03.6.A HIGH RATE OF MULTIFOCAL RELAPSE AND SUBSEQUENT POOR PROGRESSION-FREE SURVIVAL POST SALVAGE RADIATION THERAPY FOR WHO GRADE 2-3 MENINGIOMA MANAGED WITH INITIAL SURGERY ALONE

Abstract BACKGROUND Optimal initial management for patients with localised high risk meningioma remains uncertain with long natural history disease promoting the option of delaying adjuvant radiation therapy until relapse. This study assessed patterns of relapse and survival in a cohort of patients with high-risk meningioma managed with initial surgical therapy alone. MATERIAL AND METHODS Consecutive patients with meningioma referred for radiation therapy (IMRT) between January 2008-December 2021 were entered into an ethics approved database managed by the Neuro-oncology MDT. Categorisation and subsequent management plans were based by grade on WHO2007-2016 classification. Immediate or delayed referral pathway for IMRT was individualised by neurosurgical team. At time of subsequent referral for IMRT at relapse patients had tumour site / volume determined by MRI and Dotatate PET. Tumour volume, site of relapse in relation to initial cavity and number of recurrent foci of disease were recorded. For patients subsequently receiving IMRT an integrated-boost, generally 60Gy/54Gy, was used. Primary endpoints were site of relapse in relation to initial surgical cavity, number of foci, and median time from initial surgery. Secondary endpoints were median progression-free(mRFS)/overall survival(mOS) calculated from start salvage IMRT compared to cohort of intercurrent patients managed at initial diagnosis. RESULTS One hundred and five patients with meningioma were referred, with median follow-up for survivors of 3.6yrs (q1-3:1.5-7.7yrs). Median age was 59.2yrs; 59% had convexity meningioma; WHO2016 grade was G3 in 21%; Atypical(G2) in 66% and G1/no biopsy in 9% of patients. Twenty-two patients have subsequently relapsed post IMRT; with sixteen deceased for 8yrPFS and 8yrOS of 63.5% and 73.5% respectively. Forty-nine(46%) of patients were referred for IMRT at relapse, of which 39% had repeat resection prior to IMRT referral; and 14% were WHO2016 G3 at most recent resection. Based on MRI/Dotatate 61% had more than one focus of tumour around initial surgical cavity. Subsequent to salvage IMRT, fifteen of the 49 patients have had further relapse and eleven are deceased. Patients managed at relapse had worse PFS with 55.1% 8yrPFS vs 78.0% 8yrPFS (p=0.03); however equivalent OS with 68.8% 8yrOS vs 79.4% 8yrOS (p=0.62). CONCLUSION Patients with G2/3 meningioma managed with surgery alone upfront more often had relapses that were multifocal that were not managed with further salvage surgery. The subsequent progression-free survival was poor with a high rate of subsequent relapse post salvage IMRT, especially when compared to patients managed with IMRT at time of initial diagnosis.

P11.79.B MULTICENTRE MULTI-COMPONENT DATA COLLECTION TO DEFINE NEW PREDICTORS OF RELAPSE IN HIGH GRADE GLIOMA

Abstract BACKGROUND The aim of our multi-centric study is to evaluate the predictive relapse factors for high-grade glioma patients. MATERIAL AND METHODS We studied retrospectively multi-centric cohort of high-grade glioma patients, from 2009 to 2021 at three French medical centers. This data collection was carried out as part of national funding to promote the integration of AI tools into clinical oncology routine (AI.DReAM project). Clinical, pathological, genomic, and radiotherapy data, with MR images before treatment and at relapse, were collected and are being analyzed.Relapse patterns were separated into radiotherapy and radiological-related patterns. The latter were defined based on T1-gadolinium and FLAIR sequences. We distinguished local and disseminated disease. We then sub-categorized into residual growth, new local or distal lesion, multi-focal and multi-centric relapse.We underwent a uni-variate analysis with the Chi-squared test and a multivariate analysis with logistic regression to find multi-centric relapse-related factors. RESULTS Overall, 976 files were collected. In this preliminary analysis, we evaluated data from 203 patients. Out of the latter, 70% were male. 28% of the patients were aged more than 69 years. 43% of patients underwent Gross Tumor Resection, and 36% had only biopsy. Considering that of 20,7% of patients underwent Subtotal Tumor Resection, less than 10% had a resection of more than 90%.23% of patients had multi-focal disease and 16,7% had multi-centric disease. 54,6% had temporal disease making it the most frequent site, 26,6% of patients had a deep location. Ventricular contact was noted in 58% of the cases. MGMT methylation was noted in 34% of the patients.The median radiation dose received was 60Gy [33Gy-72Gy]. 98,5% of patients received Temozolomide with radiation and 80% continued it in the adjuvant setting.The median progression-free survival was 7 months, and the median overall survival was 17,6 months [3 to 92 months].The univariate analysis showed a correlation between multi-centric or bilateral initial disease and multicentric relapse pattern (p=0.015 and p=0.012 respectively). The multivariate analysis showed no correlation between our data and the multi-centric relapse. CONCLUSION The preliminary results of our study did not find an association between the analyzed data and the multi-centric relapse pattern.The challenge set is ambitious, as there are no studies yet that identify the factors associated with the multi-centric relapse pattern.Further analyses, currently in progress, are needed for the cohort of 976 patients, taking into account disease and radiotherapy volumes. The final results will be presented at the congress

Metastatic site patterns by intrinsic subtype and HER2DX in early HER2-positive breast cancer.

Even with contemporary treatment strategies, more than 10% of HER2-positive early stage breast cancer patients may experience distant metastasis as first event during follow-up. Tools for predicting unique patterns of metastatic spread are needed to plan personalized surveillance. We evaluated how molecular heterogeneity affects the pattern of distant relapse in HER2-positive breast cancer. A total of 677 HER2-positive stage I-III breast cancer patients from ShortHER trial, Cher-LOB trial, and 2 institutional cohorts were included. PAM50 molecular subtypes and research-based HER2DX scores were evaluated. The cumulative incidence of distant relapse as the first event (any site and site specific) was evaluated using competing risk analysis. Median follow-up was 8.4 years. Tests of statistical significance are 2-sided. Stage III and high HER2DX risk score identified patients at the highest risk of distant relapse as first event (10-year incidence 24.5% and 19.7%, respectively). Intrinsic molecular subtypes were associated with specific patterns of metastatic spread: compared with other subtypes, HER2-enriched tumors were more prone to develop brain metastases (10-year incidence 3.8% vs 0.6%, P = .005), basal-like tumors were associated with an increased risk of lung metastases (10-year incidence 11.1% vs 2.6%, P = .001), and luminal tumors developed more frequently bone-only metastases (10-year incidence 5.1% vs 2.0%, P = .042). When added to stage or HER2DX risk score in competing risk regression models, intrinsic subtype maintained an independent association with site-specific metastases. The integration of intrinsic molecular subtypes with stage or HER2DX risk score predicts site-specific metastatic risk in HER2-positive breast cancer, with potential implications for personalized surveillance and clinical trials aimed at preventing site-specific recurrence.

46 Patterns of Relapse and Biochemical Control in Intermediate Risk Prostate Cancer Treated with High Dose Rate Brachytherapy (HDRB) Monotherapy

46 Patterns of Relapse and Biochemical Control in Intermediate Risk Prostate Cancer Treated with High Dose Rate Brachytherapy (HDRB) Monotherapy

289. RISK FACTOR OF RELAPSE IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA WHO ACHIEVE PATHOLOGIC COMPLETE RESPONSE TO NEOADJUVANT CHEMORADIOTHERAPY

Abstract Background Controversy still exists as to the risk factors of recurrence in patients with esophageal squamous cell carcinoma (ESCC) who achieve pathologic complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) plus esophagectomy. This study aimed to investigate the patterns and risk factors for recurrence in ESCC patients with pCR after nCRT in a single center. Method Between January 2008 and December 2018 a total of 96 ESCC cases with pCR were enrolled in this study. Sterilized lymph nodes (SLN) were defined as those lymph nodes without residual tumor but with the presence of treatment response to nCRT. Recurrence patterns were investigated and then prognostic factors for recurrence-free survival (RFS) were analyzed with univariate and multivariate analyses. Results The median follow-up time was 51.5 months. Recurrence occurred in 15 cases (15.6%) with a 9.9 months median time to recurrence and a 15.6 months median survival after recurrence. The most majority of recurrent diseases developed within the first 2 years after surgery. Distant recurrences were detected in 14 cases (14.6%), in which the most common recurrence sites were supraclavicular lymph nodes and lung, followed by para-aortic lymph nodes. The mean RFS in the whole cohort was 116.6 months. Positive SLN was identified as the independently prognostic factor for worse RFS in the multivariate analysis (HR: 5.93, 95%CI: 2.09–16.86, P = 0.001). Conclusion Relapse is not rare in ESCC cases with pCR after nCRT. Distant recurrences, the predominant pattern of relapse, mostly occur with the first 2 years after esophagectomy. pCR patients with positive SLN have a higher risk for postoperative recurrence.

Impact of resection margins and para-aortic lymph node metastases on recurrence patterns and prognosis in resectable pancreatic cancer – a long-term population-based cohort study

BackgroundPancreatic cancer remains a leading cause of cancer-related death. To individualise management and improve survival, more accurate prognostic models are needed. MethodsAll patients resected for pancreatic ductal adenocarcinoma in a tertiary Swedish centre during 2009–2019 were thoroughly analysed with regards to pathological and clinical parameters including tumour grade, resection margin status, para-aortic lymph node engagement (node station 16), and systemic treatment. ResultsThe study cohort included 275 patients. Overall median survival was 21.2 months (95% CI 17.5–24.8). Year of resection, margin status (R1 subdivided into R11mm/R1ink), perineural invasion, differentiation grade, TNM stage, and adjuvant therapy were independent factors with significant impact on survival. Margin status also significantly affected recurrence-free survival and relapse patterns, with local and peritoneal relapses being associated with R1-status (p < 0.001 and p = 0.007). Presence of para-aortic lymph node metastases was associated with shorter recurrence-free survival as compared to N1 status only. ConclusionSurvival in resected pancreatic cancer is improving over time. Resection margin status is a key factor affecting recurrence patterns and prognosis. Given the poor recurrence-free survival in node station 16 metastasised patients, the rational for resection remains in doubt, and improved treatment strategies for this patient group is necessary.

Pattern and time point of relapse in locally advanced esophagogastric adenocarcinoma after multimodal treatment: implications for a useful structured follow-up

PurposeDespite improvements in multimodal treatment of locally advanced esophagogastric adenocarcinoma, the majority of patients still relapses. The impact of structured follow-up for early detection of recurrence is unclear and controversially discussed.MethodsPatients with locally advanced esophagogastric adenocarcinoma having received neoadjuvant/perioperative chemotherapy followed by tumor resection between 2009 and 2021, underwent a structured follow-up including three-monthly imaging during the first 2 years, followed by semiannual and annual examinations in year 3–4 and 5, respectively. Clinical outcome including pattern and time point of relapse was analyzed.ResultsTwo hundred fifty-seven patients were included in this analysis. In 50.2% (n = 129) of patients, recurrent disease was diagnosed, with the majority (94.6%) relapsing within the first 2 years. The most common site of relapse were lymph node metastases followed by peritoneal carcinomatosis and hepatic and pulmonary metastases. 52.7% of patients presented with symptoms at the time of relapse. Cumulative risk and time point of relapse differed significantly between patient with a node-positive tumor (ypN+) after neoadjuvant treatment (high-risk group) and patients with node-negative primary tumor (ypN0) (low-risk group). High-risk patients had a significantly inferior disease-free survival (DFS) and overall survival (OS) with 11.1 and 29.0 months, respectively, whereas median DFS and OS were not reached for the low-risk group.ConclusionsThe risk of relapse differs significantly between high- and low-risk patients. Only a part of relapses is associated with clinical symptoms. An individualized follow-up strategy is recommended for high- and low-risk patients considering the individual risk of relapse.

Machine learning‑based radiomics models for prediction of locoregional recurrence in patients with breast cancer.

Locoregional recurrence (LRR) is the predominant pattern of relapse after definitive breast cancer treatment. The present study aimed to develop machine learning (ML)-based radiomics models to predict LRR in patients with breast cancer by using preoperative magnetic resonance imaging (MRI) data. Data from patients with localized breast cancer that underwent preoperative MRI between January 2013 and December 2017 were collected. Propensity score matching (PSM) was performed to adjust for clinical factors between patients with and without LRR. Radiomics features were obtained from T2-weighted with and without fat-suppressed MRI and contrast-enhanced T1-weighted with fat-suppressed MRI. In the present study five ML models were designed, three base models (support vector machine, random forest, and logistic regression) and two ensemble models (voting model and stacking model) composed of the three base models, and the performance of each base model was compared with the stacking model. After PSM, 28 patients with LRR and 86 patients without LRR were included. Of these 114 patients, 80 patients were randomly selected to train the models, and the remaining 34 patients were used to evaluate the performance of the trained models. In total, 5,064 features were obtained from each patient, and 47-51 features were selected by applying variance threshold and least absolute shrinkage and selection operator. The stacking model demonstrated superior performance in area under the receiver operating characteristic curve (AUC), with an AUC of 0.78 compared to a range of 0.61 to 0.70 for the other models. An external validation study to investigate the efficacy of the stacking model of the present study was initiated and is still ongoing (Korean Radiation Oncology Group 2206).

Significant gut microbiota related to patterns of drinking and alcohol relapse in patients with alcoholic hepatitis undergoing stool transplant or corticosteroid therapy.

Alcohol-induced gut microbiota (GM) alterations are linked to alcohol use disorder (AUD) pathogenesis. Healthy donor stool transplant (fecal microbiota transplant [FMT]) reduced alcohol desire and improved clinical outcomes in small animal and human studies. Baseline and post-therapy-related GM changes in a real-world cohort with severe alcohol-related liver disease and AUD, patterns of drinking, and relapse have not been studied. We prospectively analyzed retrospective clinical data and stored samples to examine GM alterations in a cohort of severe alcohol-associated hepatitis (SAH) patients who underwent FMT or corticosteroid treatment followed for at least 12 months. The GM changes at baseline in the context of a pattern of drinking (binge vs. every day) and baseline and post-treatment alcohol relapse status (relapser vs. non-relapser). We identified 28 patients on FMT and 25 on corticosteroids who survived 1 year post-treatment. After necessary exclusions, the final cohort for various grouped GM analysis included 16 patients in the FMT arm and 14 on corticosteroids. Pedobacter and Streptophyta species at the commencement of treatment predicted alcohol relapse in steroid-ineligible patients receiving FMT and steroid-treated patients, respectively. At 6-12 months post-FMT, non-relapsers had elevated short-chain fatty acid-producing bacterial taxa linked with lower alcohol cravings. Alcohol relapse was significantly more in those on steroid therapy and was associated with the upregulation of the nucleotide metabolism pathway related to ethanol metabolism. We demonstrate pertinent baseline and post-treatment intestinal bacterial alterations that impact patterns of AUD patterns and relapse in SAH patients in the context of the therapy offered.

Does age affect outcome with breast cancer?

Prior data about the influence of age at diagnosis of breast cancer on patient outcomes and survival has been conflicting. Using the Breast Cancer Outcomes Unit database at BC Cancer, this retrospective population-based study identified a cohort of 24,469 patients diagnosed with invasive breast cancer between 2005 and 2014. Median follow-up was 11.5 years. We analyzed clinical and pathological features at diagnosis and treatment specific variables compared across the following age cohorts: <35, 35-39, 40-49, 50-59, 60-69, 70-79, and 80 years of age and older. We assessed the impact of age on breast cancer specific survival (BCSS) and overall survival (OS) by age and subtype. There were distinct clinical-pathological and treatment pattern differences at both extremes of age at diagnosis. Patients <35 and 35-39 years old were more likely to present with higher risk features, HER2 positive or triple-negative biomarkers, and more advanced TNM stage at diagnosis. They were more likely to undergo treatment with mastectomy, axillary lymph node dissection, radiotherapy and chemotherapy. Conversely, patients ≥80 years old were generally more likely to have hormone-sensitive HER2-negative disease, and lower TNM stage at diagnosis. They were less likely to undergo surgery or be treated with radiotherapy and chemotherapy. Both younger and elderly age at breast cancer diagnosis were independent risk factors for poorer prognosis after controlling for subtype, LVI, stage, and treatment factors. This work will help clinicians to more accurately estimate patient outcomes, patterns of relapse, and provide evidence-based treatment recommendations.

Malaria Elimination in Africa: Rethinking Strategies for Plasmodium vivax and Lessons from Botswana.

The global malaria community has picked up the theme of malaria elimination in more than 90% of the world's population in the next decade. Recent reports of Plasmodium vivax (P. vivax) in sub-Saharan Africa, including in Duffy-negative individuals, threaten the efforts aimed at achieving elimination. This is not only in view of strategies that are tailored only to P. falciparum elimination but also due to currently revealed biological characteristics of P. vivax concerning the relapse patterns of hypnozoites and conservation of large biomasses in cryptic sites in the bone marrow and spleen. A typical scenario was observed in Botswana between 2008 and 2018, which palpably projects how P. vivax could endanger malaria elimination efforts where the two parasites co-exist. The need for the global malaria community, national malaria programs (NMPs), funding agencies and relevant stakeholders to engage in a forum to discuss and recommend clear pathways for elimination of malaria, including P. vivax, in sub-Saharan Africa is warranted.

Consensus Delineation Guidelines for Pelvic Lymph Node Radiation Therapy of Prostate Cancer: On Behalf of the Francophone Group of Urological Radiation Therapy (GFRU)

Clinical target volume (CTV) delineation for pelvic lymph nodes in prostate cancer is currently based on 3 consensus guidelines with some inherent discrepancies. To improve the reproducibility in nodal delineation, the Francophone Group of Urological Radiotherapy (Groupe Francophone de Radiothérapie Urologique [GFRU]) worked toward proposing an easily applicable, reproducible, and practice-validated contouring guideline for pelvic nodal CTV. The nodal CTV data sets of a high-risk node-negative prostate cancer clinical case contoured by 86 radiation oncologists participating in a GFRU contouring workshop were analyzed. CTV volumes were defined before and after a structured presentation of literature data on lymphatic drainage pathways and patterns of nodal involvement and relapse, illustrated using a reference contour (CRef) defined by 3 GFRU experts. The consistency between the participants' contours and CRef was assessed quantitively by means of the Simultaneous Truth and Performance Level Estimation (STAPLE) method, the Dice coefficient, and the Hausdorff distance and qualitatively using a count map. These results combined with the literature review were thoroughly discussed among GFRU experts to reach a consensus. From the 86 workshop participants, the volume of the STAPLE CTV was 591 cc compared with 502 cc for CRef. The Dice coefficient of the STAPLE CTV compared with the experts' CRef was 0.736 (±0.084) before and 0.823 (±0.070) after the workshop; the standard deviation decreased from 11.5% to 8.5% over the workshop. The Hausdorff distance of the STAPLE CTV compared with the CRef was 34.5 mm (±12.4) before the workshop and 21.8 mm (±9.3) after the workshop. Four areas of significant interobserver variability were identified, and a consensus was reached. Using a robust methodology, our cooperative group proposed an easily applicable, reproducible, and practice-validated guideline for the delineation of the pelvic CTV in prostate cancer, useful for implementation in daily practice and clinical trials.

A comparison of loco-regional relapse pattern in HPV positive vs negative oropharyngeal cancers following radiotherapy; relation to pretreatment FDG-PET and radiotherapy target volumes

Background Previous studies have shown that a large proportion of relapses in head-and neck squamous cell carcinoma (HNSCC) following radiotherapy (RT) occur in the pretreatment FDG-PET avid volume (GTV-PET). The aim of the current work was to see if this was valid also in an oropharynx squamous cell carcinoma (OPSCC) only population, and to compare the loco-regional relapse pattern between HPV positive and HPV negative patients. Material and methods Among 633 OPSCC patients treated between 2009 and 2017, 46 patients with known HPV (p16) status and isolated loco-regional relapse were included. Oncologists contoured relapse volumes (RV) on relapse scans (PET/CT, CT or MR), which were thereafter deformed to match the anatomy of the planning CTs. The point of origin (center of volume) of the deformed RVs were determined and analyzed in relation to the RT target volumes (GTV-PET, GTV and CTVs). The relapse pattern was compared between HPV positive and HPV negative patients using Fischer’s exact test. Results Sixty RVs were contoured in the 46 patients. 55% (95% CI 44–67%) of relapses originated in GTV-PET, while the other RT volumes harbored 12% (5–20%) (GTV), 18% (9–28%) (high risk CTV) and 5% (0–11%) (low risk CTV) of relapses. Six relapses were found outside the RT target volumes. No significant difference in relapse pattern between HPV positive and HPV negative patients was found (p = .95). Conclusion There were no signs of difference in loco-regional relapse pattern between HPV positive and HPV negative patients. In agreement with previous findings, GTV-PET was the most frequent RT target volume of relapse.

Feasibility and long-term outcomes of post-chemotherapy-based consolidation radiotherapy in extensive stage small-cell lung cancer

BackgroundThe target definition of consolidation radiotherapy (RT) for extensive stage small-cell lung cancer (ES-SCLC) has not been standardized. This study aimed to demonstrate the feasibility of post-chemotherapy based consolidation RT in ES-SCLC. MethodsAll ES-SCLC patients without initial brain metastases who completed ≥ 4 cycles of systemic therapy at Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University from 2012 to 2021 were included in this retrospective study. We correlated the site of first recurrence to the post-chemotherapy-based radiation volume (small-field). Relapse pattern, progression-free survival (PFS) and overall survival (OS) were compared between those received and did not receive consolidation RT. ResultsA total of 152 patients were followed up for a median of 31.7 months (interquartile range [IQR], 23.9–39.6 months). The median PFS and OS of the cohort were 8.3 months (IQR, 6.1–11.2 months) and 16.2 months (IQR, 9.9–24.9 months), respectively. Thoracic consolidation RT served not only as an independent prognostic factor for improved PFS in the entire cohort, but also significantly prolonged OS in the subgroup without synchronous liver metastases. Small-field consolidation RT markedly reduced in-field recurrences (hazard ratio [HR], 0.28 [95% CI, 0.12–0.38]; P < 0.001) without increasing out-of-field recurrences (HR, 0.40 [95% CI, 0.13–1.16]; P = 0.080). No relapse was observed at the margin of the targets. Treatment-related toxicities were moderate, with grade 3 acute radiation pneumonia, radiation esophagitis, and bone marrow suppression rates of 8.3%, 3.1%, and 12.5%, respectively. No grade 5 toxicity occurred. ConclusionSmall-field consolidation RT based on post-chemotherapy volume is safe and can significantly improve local control in ES-SCLC.

Survival and Trends in Annualized Hazard Function by Age at Diagnosis Among Chinese Breast Cancer Patients Aged ≤40 Years: Case Analysis Study

Background Young breast cancer patients are more likely to develop aggressive tumor characteristics and a worse prognosis than older women, and different races and ethnicities have distinct epidemiologies and prognoses. However, few studies have evaluated the clinical biological features and relapse patterns in different age strata of young women in Asia. Objective We aimed to explore survival differences and the hazard function in young Chinese patients with breast cancer (BC) by age. Methods The patients were enrolled from West China Hospital, Sichuan University. The chi-squared test, a Kaplan-Meier analysis, a log-rank test, a Cox multivariate hazards regression model, and a hazard function were applied for data analysis. Locoregional recurrence–free survival (LRFS), distant metastasis–free survival (DMFS), breast cancer–specific survival (BCSS), and overall survival (OS) were defined as end points. Results We included 1928 young BC patients diagnosed between 2008 and 2019. Patients aged 18 to 25, 26 to 30, 31 to 35, and 36 to 40 years accounted for 2.7% (n=53), 11.8% (n=228), 27.7% (n=535), and 57.7% (n=1112) of the patients, respectively. The diagnosis of young BC significantly increased from 2008 to 2019. Five-year LRFS, DMFS, BCSS, and OS for the entire population were 98.3%, 93.4%, 94.4%, and 94%, respectively. Patients aged 18 to 25 years had significantly poorer 5-year LRFS (P&lt;.001), 5-year DMFS (P&lt;.001), 5-year BCSS (P=.04), and 5-year OS (P=.04) than those aged 31 to 35, 26 to 30, and 36 to 40 years. The hazard curves for recurrence and metastasis for the whole cohort continuously increased over the years, while the BC mortality risk peaked at 2 to 3 years and then slowly decreased. When stratified by age, the annualized hazard function for recurrence, metastasis, and BC mortality in different age strata showed significantly different trends, especially for BC mortality. Conclusions The annual diagnosis of young BC seemed to increase in Chinese patients, and the distinct age strata of young BC patients did not differ in survival outcome or failure pattern. Our results might provide strategies for personalized management of young BC.

Comparison of Clinical Outcomes, Pathologic Characteristics, and Immune-Related Features of Postradiation vs Sporadic Oral Cavity Squamous Cell Carcinoma

Postradiation oral cavity squamous cell carcinoma (OCSCC) is a common secondary malignant neoplasm affecting survivors of head and neck cancer who underwent radiotherapy. The clinical, pathologic, and immune-related features of postradiation OCSCC are poorly characterized, and treatment options are limited because of surgical difficulty and high morbidity associated with reirradiation. To determine whether postradiation OCSCC has distinctive clinical, pathologic, and immune-related features compared with demographic-matched sporadic OCSCC. This retrospective matched cohort study was conducted at a single tertiary oncology center in Hong Kong. Participants included consecutive patients with OCSCC diagnosed between 2000 and 2020. Patients with postradiation OCSCC were matched with patients with sporadic OCSCC using age, year of diagnosis, sex, and anatomic subsites. Data analysis was performed from July to December 2022. Head and neck irradiation involving the oral cavity before the diagnosis of OCSCC. The primary outcomes were relapse pattern, survival, and causes of death. Pathologic features; immunohistochemical staining for programmed death-ligand 1, PD-1, MSH6, PMS2, FOXP3, and Ki67; and mRNA expression of 31 immune-related genes were also analyzed. A total of 173 patients, 60 with postradiation OCSCC (median [IQR] age, 63.8 [53.0-71.7] years; 43 men [71.7%]) and 113 with sporadic OCSCC (median [IQR] age, 64.4 [52.8-70.6] years; 83 men [73.5%]), were included. Patients with postradiation OCSCC had a higher proportion of N0 disease than those with sporadic OCSCC (50 patients [83.3%] vs 56 patients [49.6%]). With a median (IQR) follow-up of 10.2 (1.2-20.5) years, the 10-year relapse-free survival rates were lower in patients with postradiation OCSCC than sporadic OCSCC (29.6% [95% CI, 17.1%-43.2%] vs 52.4% [95% CI, 41.8%-62.0%]; P = .04), and the same was true for overall survival (30.5% [95% CI, 17.6%-44.4%] vs 52.3% [95% CI, 41.4%-62.1%]; P = .03). All relapses in patients with postradiation OCSCC were locoregional, whereas 35.2% of relapses (12 of 34 patients) in patients with sporadic OCSCC were distant. Despite similar 10-year disease-specific survival rates between the 2 groups (68.8% [95% CI, 55.8%-81.0%] vs 67.1% [95% CI, 57.5%-76.5%]; P = .91), patients with postradiation OCSCC had excess mortality due to pneumonia and cerebrovascular events. Postradiation OCSCC exhibited more adverse pathologic features (perineural invasion, worse pattern of invasion, and tumor budding), higher PD-1 expression, and higher gene expression of CD4 and TGF-β compared with sporadic OCSCC. This retrospective matched cohort study found distinctive pathologic characteristics and relapse patterns of postradiation OCSCC compared with sporadic OCSCC, which may be attributable to the lack of adjuvant radiotherapy, aggressive biologic phenotype, and different host immune response. Further exploration of the role of immune checkpoint therapy may be justified.

Intracranial Relapse in Pediatric Sarcoma.

Advances in local control techniques, chemotherapy regimens, and imaging modalities have led to improvements in both morbidity and mortality in pediatric sarcoma patients. However, approximately one-third of patients develop disease relapse and intracranial metastasis was considered rare. The incidence of sarcoma brain metastasis is thought to have increased and is associated with grim outcomes. This was a retrospective study of 3 deidentified patient charts illustrating the possibility of the central nervous system as a potential site for pediatric sarcoma relapse and investigate the patterns of such relapses. We note this is the first report of infantile fibrosarcoma brain metastasis and a rare report of sarcoma lymph node metastasis. In addition, each patient was treated with targeted therapies, including entrectinib, Ruxolitnib, and pazopanib. Caregivers in cases 2 and 3 reported new-onset neurological manifestations before identification of new brain metastasis, indicating a lag in detection of new intracranial relapse in asymptomatic sarcoma patients. We suggest implementing a brief review of systems screening tool focused on concerning neurological manifestations to screen for new brain metastasis.

Multi-institutional Characterization of Outcomes for Pediatric and Young Adult Patients With High-Risk Myxopapillary Ependymoma After Radiation Therapy

Myxopapillary ependymoma (MPE) is a rare, typically slow-growing subtype of spinal ependymomas. There are no standard guidelines for radiotherapy and long-term outcomes after radiation, particularly patterns of relapse, for pediatric and young adult (YA) patients with MPE remain under-characterized. This is an Institutional Review Board-approved multi-institutional retrospective cohort study of 60 pediatric and YA patients diagnosed with MPE and received radiotherapy between 2000-2020. Clinical and treatment characteristics, and long-term outcomes were recorded. Site(s) of progression was compared to radiation fields. Survival outcomes were analyzed using Kaplan-Meier method. Cumulative incidence of local in-field progression (CILP) after initial radiotherapy was analyzed using Gray's method with out-of-field-only progression as a competing risk. Univariate analyses were performed using Cox proportional hazard's model. The median age at radiation was 14.8 years (range: 7.1-26.5). At time of radiotherapy, 45 (75.0%) and 35 (58.3%) patients had gross residual and multifocal disease, respectively. Forty-eight (80.0%), seven (11.7%) and five (8.3%) patients received involved field radiotherapy, craniospinal irradiation, and whole spine radiation, respectively. Median follow-up from end of radiotherapy was 6.2 years (range: 0.6-21.0). Five-year overall survival, progression-free survival, and CILP were 100%, 60.8% and 4.1%, respectively. Both local recurrences were at sites of gross residual disease. Of the eighteen out-of-field first recurrences after radiotherapy, all were superior to the initial treatment field and nine had intracranial relapse. On univariate analyses, distant-only recurrence before radiation (HR: 4.00, 95% CI: 1.54-10.43, p=0.005) was significantly associated with shorter time to progression. While the risk of recurrence within the radiation field is low, pediatric and YA patients with high-risk MPE remain at risk for recurrences in the spine above the radiation field and intracranially after radiotherapy. Future prospective studies are needed to investigate the appropriate radiation field and dose based on the extent of metastases.