Ten-year Overall Survival Research Articles

Proton-Based Radiation Therapy for Skull Base Chondrosarcomas in Children and Adolescents: 40-Year Experience From the Massachusetts General Hospital

BACKGROUNDThe literature on skull base chondrosarcoma (CHS) is scarce. We report outcomes for pediatric and young patients ≤ 22 years with base of skull (BOS) CHSs treated with proton-based radiotherapy (PBRT). METHODSWe retrospectively reviewed all patients treated with PBRT between 1981 and 2023. Primary endpoints were overall survival (OS), chondrosarcoma-specific survival (CSS), progression-free survival (PFS), local control (LC), and distal control (DC). RESULTSEighty-four patients were identified. Median age at diagnosis was 19 years (range, 6 - 22). Most patients (n=79, 94%) had conventional CHS while 5 (6%) had mesenchymal CHS. Nine patients (11%) underwent gross total resection (GTR), 64 (76%) subtotal resection (STR) and 11 patients (13%) underwent biopsy. Twenty-four (29%) patients progressed prior to radiotherapy (RT). The median prescription dose was 70 Gy (RBE) (range, 50 – 79.7). At a median follow-up of 18.0 years [interquartile range (IQR),), 9.2 –26.2] from diagnosis, 11 patients recurred (7 local, 4 distant). Six patients died of disease. Five patients died of other causes. Ten-year OS, CSS and PFS rates for all patients were 93.3%, 94.7% and 88%, respectively. Twenty-year OS, CSS and PFS rates for conventional CHS (n=79) were 93.1%, 97.1% and 89.2%, respectively. Mesenchymal histology was significantly associated with worse OS and PFS. Pre-RT tumor progression portended worse OS and CSS. Eight patients (9.9 %) experienced a late toxicity grade 3 or greater. CONCLUSIONSThis is the largest cohort of pediatric BOS CHSs in literature to date. High-dose PBRT following surgical resection achieves excellent disease control with minimal toxicity.

Long-term survival outcomes of 'watch and wait' in patients with bronchus-associated lymphoid tissue lymphoma: a multicenter real-world data analysis in Korea.

Bronchus-associated lymphoid tissue (BALT) is a rare cause of extranodal marginal zone lymphoma (MZL). Although most patients with BALT lymphoma (BALToma) show an indolent clinical course and are monitored without treatment, there are limited real-world data on the long-term outcome of "watch-and-wait' strategy in comparison with other treatments.The survival outcomes of patients newly diagnosed with BALToma at three tertiary hospitals in Korea undergoing two treatment strategies were analyzed: group A, patients who were monitored without any treatment or received only radiotherapy after diagnosis; and group B, patients receiving any kind of systemic chemotherapy after diagnosis, regardless of their history of any local treatment such as surgery or radiotherapy.Of the 67 patients included in our analysis, the 10-year progression-free survival (PFS) and 10-year overall survival (OS) rates were 65.3% and 83.2%, respectively. The 10-year PFS rates for observation or localized treatment and systemic chemotherapy were 78.7% and 56.9%, respectively (p = 0.044). Ten-year OS rates for observation or localized treatment and systemic chemotherapy were 100% and 71.7%, respectively (p = 0.016). Multivariate analysis showed that bilateral lung (HR 2.462, p = 0.047) and extrapulmonary organ (HR 4.485, p = 0.004) involvement were the only significant factors associated with poor PFS. Prognostic factor analysis for OS did not yield significant results.Patients with BALToma show a favorable prognosis, suggesting that observation or localized therapy alone may be effective for patient management. However, patients with bilateral lung or extrapulmonary involvement may require careful monitoring for disease progression and more aggressive treatment approaches.

Impact of Presenting Stage on Overall Survival in Patients Treated with Neoadjuvant Chemotherapy for Triple Negative Breast Cancer.

For operable triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), clinical prognostication and postoperative decision-making relies exclusively on whether a pathologic complete response (pCR) is achieved or not. We evaluated whether extent of disease at presentation further influenced overall survival (OS) among patients with pCR or with residual disease (RD) following NAC. Patients with stage I-III TNBC who underwent NAC were identified from the National Cancer Database from 2010 to 2019. Overall survival was assessed by disease extent using the Kaplan-Meier method and Cox proportional hazards regression for univariate and multivariable analysis. A total of 35,598 patients met inclusion criteria, and 11,967 achieved pCR. Ten-year OS was 88.5% and varied by cT and cN categoryat presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (90.9%) and was worst in those with cT3-4, cN2-3 disease (72.0%). A total of 23,631 patients had RD. Ten-year OS was 60.1% and varied by cT and cN categoryat presentation. Best 10-year OS was seen in patients with cT1-2, cN0 (73.0%) and was worst in those with cT3-4, cN2-3 disease (36.3%). Notably, OS was significantly poorer for patients with cT3-4, cN2-3 diseaseat diagnosis and pCR versus those with cT1-2 cN0 and RD (aHR 1.30, 95% confidence interval 1.03-1.63, p = 0.03). Among patients with TNBC, extent of disease at presentation was prognostic for OS independently of response to NAC. Patients with advanced stage at presentation had poorer OS even in the context of pCR. Further investigation is needed to evaluate whether additional adjuvant therapy strategies should be considered for these patients.

10-yr Results of Moderately Hypofractionated Postoperative Radiotherapy for Prostate Cancer Focused on Treatment Related Toxicity

IntroductionTo retrospectively report long term outcomes following postoperative hypofractionated radiotherapy (RT) for prostate cancer, emphasizing treatment related toxicity. Material and MethodsPatients for whom adjuvant or salvage RT was indicated after prostatectomy were treated with a course of moderate hypofractionation consisting in the delivery of 62.5 Gy in 25 fractions (2.5 Gy per fraction) on the prostate bed in 5 consecutive weeks (EQD21.5 = 70 Gy) by means of 3D-CRT in most of them. Androgen deprivation therapy (ADT) was allowed at physician's discretion. Patients were evaluated for urinary and rectal complications according to the Common Terminology Criteria for Adverse Events v4 (CTCAE v.4). Overall survival (OS), biochemical recurrence free survival (bRFS), and metastasis-free survival (MFS) were estimated using the Kaplan–Meier method. ResultsOne hundred and ten patients with a median age of 67 years (range 51-78) were enrolled. The majority of them (82%) had adverse pathologic features only, while 31 (28%) had early biochemical relapse. Median PSA level before RT was 0.12 ng/mL (range 0-9 ng/mL). Median time from surgery was 4 months (range 1-136 months). Twenty-eight patients (25.4%) also received ADT. At a median follow up of 103 months (range 19-138 months), late Grade 3 and Grade 4 rectal toxicity were 0.9% (1 case of hematochezia) and 0.9% (1 case of fistula), respectively, while late Grade 3 GU side effects (urethral stenosis) occurred in 9 cases (8%). No late Grade 4 events were observed, respectively. Ten-year OS, b-RFS and MFS were 77.3% (95%CI: 82.1%-72.5%), 53.3% (95%CI: 59.9%-47.6%), and 76.7% (95%CI: 81.2%-72.2%), respectively. ConclusionOur study provides long term data that a shortened course of postoperative RT is as safe and effective as a long course of conventionally fractionated RT and would improve patients’ convenience and significantly reduce RT department workloads.

Nine-Week Versus One-Year Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 10-Year Update of the ShortHER Phase III Randomized Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We present the final analysis of the phase III noninferiority, randomized ShortHER trial comparing 9 weeks versus 1 year of adjuvant trastuzumab with chemotherapy in patients with human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (BC). Women with HER2+ BC were randomly assigned to anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or 9-week trastuzumab (arm B, short). Here, we report the second coprimary end point overall survival (OS), updated disease-free survival (DFS), and outcomes according to hormone receptor status, age, and nodal status. At a median follow-up of 9 years, 10-year DFS is 77% versus 78% in the long versus short arm, respectively. Ten-year OS is 89% versus 88% in the long versus short arm, respectively. 10-year DFS rates in the long versus short arm according to nodal status are N0 81% versus 85%; N1-3 77% versus 79%; and N4+ 63% versus 53%. Ten-year OS rates in long versus short arm according to nodal status are N0 89% versus 95%%; N1-3 92% versus 89%; and N4+ 84% versus 64%. The updated analysis of the ShortHER trial shows that 1-year trastuzumab is the standard treatment for patients with HER2+ early BC as noninferiority cannot be claimed. However, numerically, the differences for the patients at low or intermediate risk (N0/N1-3) is negligible, while patients with N4+ have a clear benefit with 1-year trastuzumab.

Utility of Bone Marrow Biopsies for Basal Stratification and Response Assessment in a Large Series of Real Life Follicular Lymphoma Patients

Introduction: Bone marrow biopsies (BMB) are usually performed before/after therapy to confirm complete response (CR) in follicular lymphoma (FL) patients. Up to 60% of patients may have bone marrow infiltration, that can change Ann Arbor stage, assigning the highest disease stage. Also, BMB infiltration is included in several prognostic indexes such as FLIPI2 and PRIMA-PI. Persistence of bone marrow disease after treatment is associated with worse outcome. Aim: The main objective is to establish whether BMB adds value in assessing response or predicting progression-free survival (PFS) and overall survival (OS) in previously untreated FL subjects from a large, Spanish unicentric retrospective cohort. Results: From 2001-2022 we recorded data from 260 newly diagnosed FL grade 1-3A from Hospital 12 de Octubre.The median age at diagnosis was 64 years (range 27-90) and 34 patients (13%) had grade 3A FL. Most patients (67%) had advanced Ann-Arbor stage and 45,4% presented bone marrow infiltration (111/244). 104 (40%) patients were considered suitable for a watchful waiting policy; of them, 52 (50%) never required systemic treatment during follow-. 132 patients (61% of those receiving treatment) were treated with R-CHOP or R-CVP, 44 (21%) received R-bendamustine and 20 (10%) rituximab monotherapy. In 114 patients (55%) PET/CT was done at the moment of diagnosis and to evaluate the response after treatment. The other were evaluated by CT. Basal bone marrow biopsy was essential in the diagnostic of 3 patients that only presented FL in BM. In addition, BMB upgraded disease stage in 9 (3.7%) that presented <3 nodal areas involved, without other extranodal infiltration. Basal BMB positive was predictive of worse PFS and OS in univariate analysis (HR = 1.69; 95%CI 1.04-2.76 and HR = 1.98; 95%CI 1.10-3.60, respectively). Ten-years PFS was 72% in patients without BM involvement vs 51% in patients with BM infiltration (HR= 1.7, p=0.034) ( Figure 1) and, Ten-years OS was 82% vs 62%, respectively. In 82 of 104 patients (79%) with basal BM infiltration, a BMB was performed after finishing induction treatment. In the other 22 patients BMB was not performed because of evidence of progression (n=10) or because of unknown causes (n=12). 12 (15%) of 82 patients evaluated remained BMB positive by histology. Globally, and independent of the image response assessment, the reassessment of BM did not confer prognostic differences in patients in whom it was performed and in those who were not (p= 0.92). Nevertheless, patients with post-induction BM infiltration (n=12) showed worse outcomes than those without post-induction BM involvement (n=70) (HR=3.9, 95CI 1.8-8.5) ( Figure 2). Only 3 of 59 treated patients (5%) had positive baseline BMB, CR on imaging, and subsequent positive BMB, and therefore that affected response assessment. All 3 patients were evaluated by CT because they received treatment in 2004-2007. Of subjects with CR on imaging (n = 73), PFS and OS were not significantly different among those with negative BMB to confirm CR (n = 59) versus those without repeat BMB (n = 11); PFS: HR=1.12, 95%CI 0.38-3.31, p = 0.83; OS: HR=1.66 95%CI 0.46-6.07, p = 0.44) Conclusion: In a real-life study of newly diagnosed FL we conclude that BMB adds little value in the basal evaluation; with only 4.% of patients who were thought to have early stage disease before bone marrow evaluation. Besides, despite BM infiltration confers prognostic value, to date there are no differences in the management of these patients based on this finding. In relation to response assessment, BMB adds little value to response assessment. Only 3 patients (1.4%) in our series presented CR on imaging and BM infiltration postinduction. Moreover, none of them was evaluated by PET. With this data, we strongly recommend performing diagnostic BMB in FL in scenarios in which it may change management including confirmation of limited stage and assessment of cytopenias. Prospective studies are necessary to see its value during follow- up. Nevertheless, with new techniques as LiqBio MRD, removing this study from reassessment might be an option that would reduce patient discomfort and resource utilization.

Cumulative Incidence, Predictors, and Outcomes of Transformation to Diffuse Large B-Cell Lymphoma in a Prospective Cohort of Patients with Marginal Zone Lymphoma

Background: Although marginal zone lymphoma (MZL) typically exhibits an indolent course, transformation to diffuse large B-cell lymphomas (DLBCL) is associated with a poorer outcome and remains a clinical challenge in managing patients with MZL. The limited existing literature reports various cumulative incidence rates, ranging from 2.5% and 4.7% (Finnish Cancer Registry, 1995-2018) to 6.6% and 8.4% (Florida Cancer Registry, 1995-2016) at 5 and 10-years, respectively, likely in part driven by varying study designs, ascertainment, and study population. Similarly, reported outcomes after transformed MZL (tMZL) have been variable. We evaluated the cumulative incidence of histological transformation (HT) to LBCL in a well-characterized prospective cohort of MZL patients from the upper Midwest, USA, and overall survival (OS) after transformation. Methods: Patients ≥ 18 years old with newly diagnosed MZL were prospectively enrolled in the University of Iowa/Mayo Clinic Molecular Epidemiology Resource (MER) cohort from 2002-2015. Clinical and treatment data were abstracted from medical records using a standard protocol. Patients were actively followed for retreatment, transformation, and death through 2022. Pathology was classified according to WHO 4/4R, including all transformations. The cumulative incidence of HT to LBCL was determined using death as a competing risk. Time to HT (TTHT) was defined as time from the date of MZL diagnosis to the date of transformation. We evaluated potential predictors of HT using a stepwise approach, and derived hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional hazards models. To assess predictors of OS after HT, patients ≥ 18 years old with newly diagnosed tMZL (into DLBCL) at Mayo Clinic between 1995 and 2002 (N=7) were combined with the MER cases. Results: We identified 524 patients with MZL in the MER cohort: 362 extranodal (EMZL; lung 18%, stomach 16%, orbit 13%, parotid 10%, skin 10%), 84 splenic (SMZL), and 78 nodal (NMZL). The median age at diagnosis was 63 years (range 18-92); 56% were female, and 83% were non-Hispanic white. During a median follow-up of 18.8 years (95% CI 16.7, NA), there were 25 HT (including 8 patients under observation) and 158 deaths. Eight Ten-year OS was 67% and 77% in the groups with and without HT, respectively. The overall cumulative incidence of HT was 1.5% at 2 years after diagnosis, 2.9% at 5 years, 4.5% at 10 years, and 5.7% at 15 years (Panel 1). The cumulative incidence of HT varied by subtype (e.g., at 5 years: 2%, 4% and 6%, in EMZL, NMZL and SMZL, respectively; Panel 2). The median time to HT also varied by subtype: 76 months (interquartile range (IQR) 43, 81) for EMZL, 30 months (IQR 16, 52) for SMZL, and 18 months (IQR 14, 23) for NMZL. In univariable analysis, predictors of HT were Stage III/IV (HR=3.4, 95% CI 1.36-8.53, p=0.009), elevated LDH (HR=2.98, 95% CI 1.25-7.12, p=0.014), and presence of ≥2 extranodal sites (HR=2.69, 95% CI 1.22-5.94, p=0.014). In multivariable analysis, elevated LDH was the only non-composite predictor of HT (HR=2.65, 95% CI 1.08-6.52, p=0.034). MALT-IPI score 2-3 (HR=3.61, 95% CI 1.06-12.25, p=0.040) and FLIPI score 3-5 (HR=2.19, 95% CI 1.22-8.22, p=0.018) also predicted HT. We analyzed OS after HT in 32 cases of tMZL (21 tEMZL, 7 tSMZL, 4 tNMZL). At HT, median age was 68 years (range 39-89); 24 (80%) patients presented with stage III/IV disease, 11 (58%) with elevated LDH, 12 (55%) with hemoglobin <12g/dL, 3 (14%) with platelet count <100x10 9/L and 9 (39%) with biopsy-proven bone marrow involvement. Twenty-six (81%) were treated with a systemic therapy, mainly CHOP-backbone therapy (R-CHOP n=13, CHOP n=4, R-EPOCH n=3, lenalidomide-R-CHOP n=1). Among these patients, the overall response rate was 85% (n=22/26). Three of the 4 non-responders died within 1 year. At last follow-up, 18/32 (56%) patients had died, and 6/13 (46%) alive patients had relapsed (MZL 3/6, DLBCL 3/6). After HT, 2-, 4- and 10-year OS were 76%, 55% and 55%, respectively. In univariable analysis, the only predictor of OS at HT was age ≥70 (HR 3.57 ,95% CI 1.34-9.48, p=0.011). Conclusion: In this North American prospective cohort of mainly non-Hispanic White patients, we found a low cumulative incidence of HT in MZL of 2.9% and 4.5% at 5- and 10-year, which was consistent with the Finnish findings (Kalashnikov et al., 2023). At HT, age was associated with OS and there was a high response rate to CHOP-backbone therapies.

Survival in patients diagnosed with melanoma in situ compared to the general population. A Swedish population-based matched cohort study

The incidence of melanoma in situ (MIS) is increasing even more rapidly than the incidence of cutaneous malignant melanoma (CMM). No previous studies have in detail investigated the survival in individuals diagnosed with MIS compared to the general population. This population-based study included individuals with MIS diagnosed in Sweden between 2001 and 2010 and randomly selected MIS-free comparators matched on age, sex and county of residence. Exclusion criterion was a previous CMM. Data on socioeconomic status (SES) including educational level, income and marital status, comorbidity and cause of death were obtained from population-based registers. Overall survival (OS) was estimated by the Kaplan-Meier method. The mortality risk adjusted for SES and comorbidity was assessed by multivariable Cox regression analyses. The survival analyses included 7963 cases and 39,662 comparators. Median age at MIS diagnosis were 63 (IQR 50-75) and 67 (IQR 57-76) years in women and men respectively. Median follow-up time was 120 months (IQR 102-152 months). In individuals with MIS, the ten-year OS was 77% (95% CI 0.76-0.78) compared to 72% (95% CI 0.72-0.73) in comparators. The MIS patients had a higher SES and lower comorbidity burden than the comparators. In a fully adjusted multivariable analysis, including 7772 cases and 38,103 comparators, the mortality was significantly lower in women with MIS (HR 0.88, 95% CI 0.82-0.94) compared to the background population. The corresponding estimate in men was HR 0.94 (95% CI 0.88-1.0). The risk of melanoma-related deaths during the study period was ten-fold higher in MIS patients. Despite being at increased risk of developing CMM, MIS patients had a better OS compared to their matched comparators from the background population, findings which could not fully be explained by differences in SES and comorbidity. Our results are reassuring and should be communicated to patients who have been diagnosed with MIS. Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond, Mats and Stefan Paulsson Trust, Medicon Village, Lund and Uppsala University Hospital (ALF).

Thermally boosted interstitial high-dose-rate brachytherapy in high-risk early-stage breast cancer conserving therapy - large cohort long-term results.

Early-stage high-risk breast cancer (BC) is standardly treated with breast-conserving therapy (BCT), combined with systemic therapy and radiotherapy (RT) ± tumor bed boost, e.g., with interstitial high-dose-rate brachytherapy (HDR-BT). To improve local recurrence rate (LRR), BT radiosensitization (thermal boost, TB) with interstitial microwave hyperthermia (MWHT) may be an option. The paper aims to report a retrospective single-institutional study on 5- and 10-year local control (LC), distant metastasis-free survival (DMFS), disease-free survival (DFS), overall survival (OS), cosmetic outcome (CO), and late toxicity (fibrosis, fat necrosis) after thermally enhanced HDR-BT boost to the BC tumor bed. In 2006-2018, 557 early-stage (I-IIIA) high-risk BC patients were treated with BCT. If indicated, they were administered systemic therapy, then referred for 40.0-50.0 Gy whole breast irradiation (WBI) and 10 Gy interstitial HDR-BT boost (group A). Eligible patients had a single MWHT session preceding BT (group B). Based on present risk factors (RF), medium-risk (1-2 RF) and high-risk subgroups (≥ 3 RF) were formed. Patients were standardly checked, and control mammography (MMG) was performed yearly. Breast cosmesis (Harvard scale) and fibrosis were recorded. LC, DMFS, DFS, and OS were statistically analyzed. Out of 557 patients aged 57 years (26-84), 364 (63.4%) had interstitial HDR-BT boost (group A), and 193 (34.6%) were preheated with MWHT (group B). Patients in group B had a higher clinical stage and had more RFs. The median follow-up was 65.9. Estimated 5-year and 10-year LC resulted in 98.5% and 97.5%, respectively. There was no difference in LC, DMFS, DFS, and OS between groups A and B and between extracted high-risk subgroups A and B. Five- and ten-year OS probability was 95.4% and 88.0%, respectively, with no difference between groups A and B. Harvard criteria-based CO assessment revealed good/excellent cosmesis in 74.9-79.1%. Tumor bed hardening was present in 40.1-42.2%. Asymptomatic fat necrosis-related macrocalcifications were detected in 15.6%, more frequently in group B (p = 0.016). Thermally boosted or not, HDR-BT was locally highly effective as part of combined treatment. Five- and ten-year LC, DMFS, DFS, and OS were high and equally distributed between the groups, although TB was prescribed in more advanced one with more RFs. TB did not influence CO and fibrosis. TB added to late toxicity regarding asymptomatic fat necrosis detected on MMG.

The Effect of Clinical (Anatomical) and Prognostic Stage Groups on Survival in Patients Diagnosed with Breast Cancer: MULTI-Center Study Results, TROD Breast Cancer Study Group

The American Joint Committee on Cancer (AJCC) anatomic stage groups have arguably been the most powerful method in predicting breast cancer outcomes. In the present study, we aimed to determine the differences between anatomical stage and clinical prognostic stage groups, which were obtained by adding biological markers such as histologic tumor grade, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 status to patients diagnosed with breast cancer, the rate of change in stage, and the effect of stage change on survival. The study protocol was sent to all radiation oncology centers in Türkiye. Four centers enrolled their patients to the study. A total of 1470 stage I-III breast cancer patients with complete information on biological markers (histologic tumor grade, hormone receptor, and c-erb B2 receptor status), haven't been treated with neoadjuvant therapy were included to the study and evaluated retrospectively. The 8th edition of AJCC consolidated biological markers in to clinical prognostic stage groups. Kaplan-Meier curves were used to estimate survival. The log-rank test was used to compare the difference between groups. The Cox proportional-hazards regression model was used to determine the association between anatomic-prognostic stage, disease-free survival (DFS), and overall survival (OS). The median follow-up time was 82 (6-237) months. Median age of the patients was 52 years (20-88) and 865 cases (58.8%) were in the postmenopausal period. The axillary lymph node status was negative (N0) in 765 patients (52.1%). Tumor grade was grade I in 200 patients (13.6%), grade II in 812 patients (55.2%) and grade III in 452 patients (30.7%). Estrogen receptor status was positive in 1247 patients (84.8%), PR status was positive in 1178 patients and Her2-neu status was positive in 207 patients (14.1%). A stage change has been identified in a total of 777 patients (52.9%). Compared with the anatomic stage groups, application of the clinical prognostic stage groups assigned 46.4% cases lower and 6.5% cases higher stage. Five- and ten-year OS and DFS rates of the patients are 73.7%, 44.3% and 91.9%, 86.3% respectively. Age (p<0.001), tumor grade (p<0.001), ER status (p<0.001), PR status (p<0.001), cerbB2 receptor status (p = 0.025) were found to be statistically significant variables in multivariable analysis for OS. For DFS, multivariable analysis showed that age (p = 0.027), tumor grade (p = 0.005), anatomical stage (p<0.001) and assigned to higher stage (p = .001) were statistically significant variables. Hormone receptors and c-erb B2 receptor status are independent variables which impact OS and DFS in our patient group which is mostly consisted of early-stage cases according to anatomical stage. In prognostic staging, upstaging stands out as an independent prognostic factor for DFS. The 8th edition of AJCC prognostic stage groups determines the prognosis much better in our patient cohort.

Prognosis of squamous cell carcinoma of the breast by biological subtypes and the efficacy of radiotherapy: The Japanese Breast Cancer Registry analysis.

561 Background: Primary squamous cell carcinoma (SCC) of the breast is a rare disease, accounting for about 0.1% of all breast cancers. We aimed to determine the clinical features and prognosis of breast SCC, and the effect of radiotherapy by biological subtypes using the Japanese Breast Cancer Registry. Methods: We conducted a matched-pair analysis of 350,977 breast cancer patients with SCC or invasive ductal cancer (IDC) in the Japanese Breast Cancer Registry between 2004 and 2014. Inclusion criteria were female breast cancer patients who underwent surgery with stage I–III diseases, SCC or IDC, and age ≥ 18. Patients who received preoperative radiotherapy were excluded. We performed 1:1 SCC-IDC exact matching analysis by predominant subtypes in SCC: ER(-) and PgR(-)/HER2(-) or ER(+) and/or PgR(+)/HER2(-). Overall survival (OS), breast cancer-specific survival (BCSS), recurrence-free survival (RFS), and first locoregional or distant metastasis recurrence incidence were compared between IDC and SCC by Kaplan-Meier methods and log-rank test. In-field area recurrence was compared between those who received radiotherapy and those who did not. Results: We included 452 SCC and 182,707 IDC patients for the analysis. SCC patients were more likely to present with advanced stage disease compared to those with IDC. Among SCC patients, 59% was ER(-)/PgR(-)/HER2(-), 19% was ER(+)/PgR(+)/HER2(-), 8% was ER(-)/PgR(-)/HER2(+), 2% was ER(+)/PgR(+)/HER2(+), and 12% was data missing. Ten-year OS, BCS, and RFS rates were 70%, 80%, and 66% in SCC, and 88%, 93%, and 81% in IDC, respectively, and SCC carried a significantly worse prognosis than IDC (all P &lt; 0.001). For exact-matched analysis, 10-year BCS of ER(-)/PgR(-)/HER2(-) SCC patients was significantly worse than IDC (P = 0.02), whereas there were no significant differences between SCC and IDC of ER(+)/PgR(+)/HER2(-) patients in OS, BCS, and RFS. Among patients who received radiotherapy, no difference was found in in-field area recurrence between SCC and IDC in either ER(-)/PgR(-)/HER2(-) or ER(+)/PgR(+)/HER2(-) subtype. Conclusions: SCC of the breast was often diagnosed in an advanced stage and had a worse prognosis than IDC. More than half of them were triple-negative subtype. In the triple-negative subtype, SCC was an independent poor prognostic factor. No significant differences in in-field area recurrence after radiotherapy between SCC and IDC suggested that the effect of radiotherapy on local control for SCC was similar to IDC.

Pure Tubular Breast Carcinoma: Clinicopathological Characteristics and Clinical Outcomes.

Tubular breast carcinoma (TBC) is a rare subtype of breast carcinoma (BC) with a good prognosis. In this study, we aimed to assess the clinicopathological characteristics of pure TBC (PTBC), analyze factors that may influence long-term prognosis, examine the frequency of axillary lymph node metastasis (ALNM), and discuss the need for axillary surgery in PTBC. Fifty-four Patients diagnosed with PTBC between January 2003 and December 2020 at Istanbul Faculty of Medicine were included. Clinicopathological, surgical, treatment, and overall survival (OS) data were analyzed. A total of 54 patients with a mean age of 52.2 years were assessed. The mean size of the tumor was 10.6 mm. Four (7.4%) patients had not undergone axillary surgery, while thirty-eight (70.4%) had undergone sentinel lymph node biopsy and twelve (22.2%) had undergone axillary lymph node dissection (ALND). Significantly, four (33.3%) of those who had undergone ALND had tumor grade 2 (p = 0.020) and eight of them (66.7%) had ALNM. Fifty percent (50%) of patients who were treated with chemotherapy had grade 2 and multifocal tumors and ALNM. Moreover, the frequency of ALNM was higher in patients with tumor diameters greater than 10 mm. Median follow-up time was 80 months (12-220). None of the patients had locoregional recurrence, but one patient had systemic metastasis. Furthermore, five-year OS was 97.9%, while ten-year OS was 93.6%. PTBC is associated with favorable prognosis, good clinical outcomes and high survival rate, with rare recurrences and metastases.

Aggressive Pursuit of No Evidence of Disease Status in Hepatoblastoma Improves Survival: An Observational Study

BackgroundThe utility of repeated surgical interventions in hepatoblastoma to achieve no evidence of disease (NED) is not well-defined. We examined the effect of aggressive pursuit of NED status on event-free (EFS) and overall survival (OS) in hepatoblastoma with subgroup analysis of high-risk patients. MethodsHospital records were queried for patients with hepatoblastoma from 2005 to 2021. Primary outcomes were OS and EFS stratified by risk and NED status. Group comparisons were performed using univariate analysis and simple logistic regression. Survival differences were compared with log-rank tests. ResultsFifty consecutive patients with hepatoblastoma were treated. Forty-one (82%) were rendered NED. NED was inversely correlated with 5-year mortality (OR 0.006; CI 0.001–0.056; P < .01). Ten-year OS (P < .01) and EFS (P < .01) were improved by achieving NED. Ten-year OS was similar between 24 high-risk and 26 not high-risk patients when NED was attained (P = .83). Fourteen high-risk patients underwent a median of 2.5 pulmonary metastasectomies, 7 for unilateral disease, and 7 for bilateral, with a median of 4.5 nodules resected. Five high-risk patients relapsed, and three were salvaged. ConclusionsNED status is necessary for survival in hepatoblastoma. Repeated pulmonary metastasectomy and/or complex local control strategies to obtain NED can achieve long-term survival in high-risk patients. Level of evidenceLevel III – Treatment Study - Retrospective Comparative Study.

Long term outcome of complex surgical resection and reconstruction for rare thoracic cancers.

Complex surgical resection and reconstruction for rare thoracic cancers (RTCs) represent a major challenge, given their very low frequency, extreme variability of presentation, multi-modality treatment options and inadequate outcome prediction. We analysed the experience of a tertiary referral centre on a consecutive series of patients with thoracic germ cell tumours, thymomas and sarcomas, with the aim of reporting the long-term outcome by cancer type and complexity of surgical procedures. From Jan 2003 to Dec 2018, 768 surgical procedures were performed with curative intent on 644 RTC patients. Study endpoints were: post-operative hospital stay (Pod), 30-day and 90-day mortality, 5-year and 10-year overall survival (OS). Median follow-up of alive patients was 7.2 years. Median Pod was 7 days, with a 1.2% 30-day and 2.9% 90-day mortality. OS was 90.8% at one year, 74.2% at five years and 62.8% at 10 years. Ten-year OS was 73.0% in low, 65.3% in intermediate, and 55.6% in high complexity score (Log-rank tests p<0.0001); 66.6% in patients with one or two reconstructions and 46.4% in patients with three or more reconstructions (p<0.0001); 46.0% with vascular and 50.0% with chest wall reconstruction; 71.8% in germ cell tumours, 64.6% in thymoma and 51.3% in sarcoma (p<0.0001). Complex surgical resection and reconstruction was associated with acceptable 90-day mortality and good 10-year survival in all RTC types. A predictive score based on surgical complexity and cancer type can help the clinical decision making.

Long-term outcomes and effects of hypofractionated radiotherapy in microinvasive breast cancer: Analysis from a randomized trial

PurposeThe natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation. Methods1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.5Gy in 16 daily fractions, or 50Gy in 25 daily fractions after BCS. An analysis of patients with T1mi tumors compared with T1a-2 disease was performed. Kaplan-Meier estimates of local recurrence (LR), distant recurrence, and overall survival (OS) were compared using the log-rank test. ResultsMedian follow-up was 12 years. T1mi was found in 3% (n = 38) of patients. The 10-year LR rate was 22.6% in T1mi vs. 6.9% in T1a-2 breast cancer [hazard ratio (HR) = 3.73; 95% confidence interval (CI): 1.93, 7.19; p < 0.001]. The 10-year risk of distant recurrence was 5.1% for T1mi, and 12.1% for T1a-2 disease (HR = 0.56; 95% CI: 0.19, 1.84; p = 0.36). Ten-year OS was 91.5% in T1mi and 84.4% in T1a-2 disease, (HR = 0.48; 95% CI: 0.18, 1.30; p = 0.14). Rates of LR did not differ whether treated by hypofractionation or conventional fractionation (HR = 1.21; 95% CI: 0.35, 4.18; p = 0.77). ConclusionsThe risk of LR was considerably higher in patients with T1mi compared to T1a-2 tumors, but OS remained very good. Future research should evaluate the utility of wider local excision and boost radiation to optimize local control for microinvasive breast cancer.

Ten-year survival of neoadjuvant dual HER2 blockade in patients with HER2-positive breast cancer

BackgroundDual anti-HER2-targeted therapy in breast cancer (BC) significantly increased the rate of pathological complete response (pCR) compared to single blockade when added to chemotherapy. However, limited data exist on the long-term impact on survival of the additional increase in pCR. MethodsNeoadjuvant lapatinib and/or trastuzumab treatment optimisation (NCT00553358) is an international, randomised, open-label, phase III study investigating the addition of lapatinib to chemotherapy plus trastuzumab in HER2-positive early BC. Ten-year event-free survival (EFS), overall survival (OS) and safety were assessed on intention-to-treat population. The association between pCR and EFS or OS was investigated in landmark population. ResultsA total of 455 patients were randomised to receive lapatinib (154), trastuzumab (149) or the combination (152). Ten-year EFS estimates were 63% (95% confidence interval [CI], 54%–71%) in the lapatinib group, 64% (95% CI, 55%–72%) in the trastuzumab group and 67% (95% CI, 58%–74%) in the combination group. Ten-year OS rates were 76% (95% CI, 67%–83%), 75% (95% CI, 66%–82%) and 80% (95% CI, 73%–86%) in the lapatinib, trastuzumab and combination groups, respectively. Women who achieved a pCR had improved EFS (hazard ratio 0.48, 95% CI, 0.31–0.73) and OS (hazard ratio 0.37, 95% CI, 0.20–0.63) compared with those who did not. The numerical difference in survival according to pCR status was greater in women treated with the combination and those with hormone-receptor-negative tumours. There were no new or long-term safety concerns. ConclusionsPatients with HER2-positive BC showed a durable survival benefit of neoadjuvant anti-HER2, irrespective of treatment arm. Patients who achieve pCR have significantly better outcomes than patients without pCR.

Melanomas in children and adolescents: Clinicopathologic features and survival outcomes

Melanoma in the first two decades of life is uncommon and poorly understood. To assess clinicopathologic features and survival of children (≤11 years) and adolescents (12-19years) diagnosed with melanoma. A pooled cohort of 514 patients was analyzed (397 Dutch, 117 Australian; 62 children, 452 adolescents). Pathology reports were re-evaluated to determine melanoma subtypes. Multivariable Cox models were generated for recurrence-free survival (RFS) and overall survival (OS). Melanoma subtypes were conventional melanoma (superficial spreading, nodular, desmoplastic, acral lentiginous), spitzoid melanoma, and melanoma associated with a congenital nevus in 428, 78, and 8 patients, respectively. Ten-year RFS was 91.5% (95%CI 82.4-100%) in children and 86.4% (95%CI 82.7-90.3%) in adolescents (p=0.32). Ten-year OS was 100% in children and 92.7% (95%CI 89.8-95.8%) in adolescents (p=0.09). On multivariable analysis possible only for the adolescent cohort due to the small number of children, ulceration status and anatomic site were associated with RFS and OS, whereas age, sex, mitotic index, sentinel node status and melanoma subtype were not. Breslow thickness >4mm was associated with worse RFS. Retrospective study. Survival rates for children and adolescents with melanomas were high. Ulceration, head or neck location and Breslow thickness >4mm predicted worse survival in adolescents.

Nodular Lymphocyte Predominant Hodgkin Lymphoma with Splenic Involvement Is Characterized By Inflamed Tumor Microenvironment, High Expression of Checkpoint Molecule Gene-Signature and Adverse Outcome

Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy characterized by infrequent neoplastic cells embedded in an immunologically active tumor microenvironment (TME). Histologically, NLPHL can be divided into classical (Fan A-B) and variant (Fan C-F) growth patterns. Clinical course is generally indolent, and the majority of patients present with limited stage disease. However, advanced stage with splenic involvement and variant histology are known to be associated with more aggressive disease. The molecular features underlying this association remain unknown. To gain further insights into disease biology, we recruited NLPHL cases as part of the Atlas of Blood Cancer Genomes (ABCG) initiative, a consortium consisting of 26 institutions. Design: We collected comprehensive clinicopathological data including splenic involvement from 135 NLPHL patients, with centralized review performed by a panel of dedicated hematopathologists to ensure accurate diagnosis per 2016 WHO criteria. We performed RNA sequencing on formalin-fixed paraffin-embedded (FFPE) diagnostic tumor lymph nodes (n=100) and enumerated tumor-infiltrating immune cell compositions using FARDEEP with signature matrix LM22 from CIBERSORT. In addition, we performed gene set enrichment analysis to compare molecular pathways between the patients with and without splenic involvement. The Kaplan-Meier method was used to calculate overall survival (OS) and progression free survival (PFS) probabilities, and the log-rank test was used for comparisons between groups. Continuous variables were compared using the Wilcoxon rank-sum test. Results: The median age at diagnosis was 42 years (range 5-80 years). Most patients were males (n=96; 71%) and had limited stage disease (n=96, 74%). Splenic involvement was present in 17 patients (13%). Histologic growth pattern was available for 97 cases, 41 (42%) with variant and 56 (58%) with classical histology. Variant histology was enriched in the patients with splenic involvement. Thirty-five (28%) relapses and 5 (3.9%) transformations occurred during a median follow-up of 80 months (range 0.36-604 months). Ten-year OS and PFS rates for the whole cohort were 86% (95% CI, 78-95%) and 59% (95% CI, 50-71%), respectively. Patients with splenic involvement at diagnosis tended to have inferior outcome at 10 years compared with those without splenic involvement (PFS 40% vs 62%, P=0.129; OS 79% vs 88%, P=0.0553). According to in silico immunophenotyping, NLPHLs with splenic involvement were characterized by a lower proportion of naïve B cells and increased proportions of CD8+ T cells and M1-macrophages compared to the NLPHLs without splenic involvement (P<0.001 for all comparisons). Moreover, splenic involvement was associated with higher expression of checkpoint protein-encoding genes, including PDCD1 (PD-1), CD274 (PD-L1), CTLA4, LAG3, HAVCR2 (TIM-3) and TIGIT (Figure 1; P<0.001). Finally, we found a strong association between splenic involvement and gene expression profile related to inflammatory response (P<0.001), response to interferon gamma (P<0.001) and complement pathways (P<0.001). Conclusion: Our study represents the largest comprehensive clinical and transcriptomic analyses of NLPHL to date. The results demonstrate that NLPHLs with splenic involvement are characterized by inflamed TME with high expression of checkpoint molecule gene-signature and are associated with inferior outcomes. Figure 1. Unsupervised clustering for expression of checkpoint genes stratified by spleen involvement. Samples are ordered by the sum of normalized checkpoint gene expression values (checkpoint score) Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Ten-year conditional probability of survival for patients with ovarian cancer: A new metric for the new millennium (480)

Objectives: To demonstrate the utility of conditional probability of survival (CPS) as a metric in analyzing survival outcomes for women with ovarian cancer. Methods: We analyzed the records of all patients (pts) with newly diagnosed high-grade epithelial ovarian cancer who underwent treatment at our institution from January 2001 to December 2009. Pts lost to follow-up were excluded if they had less than three years of follow-up. CPS was defined as the probability of surviving additional years (y) based on the condition that a patient had already survived at a given time (x): S(x + y)/S(x). Confidence intervals (CIs) were estimated using a variation of Greenwood’s formula. Results: A total of 916 pts met the inclusion criteria. The median age at diagnosis was 60 years (range: 25-95) with 37% (337/916) <65 years old (yo). FIGO stage was as follows: stage I 14% (132/916), stage II 6% (59/916), stage III 57% (519/916), and stage IV 23% (206/916). Histology was high-grade serous in 83% pts (759/916). Among the 907 pts who underwent surgical management, 64% (584/907) had a primary debulking surgery, 16% (143/907) had an interval debulking after neoadjuvant chemotherapy and 20% (180/907) underwent staging. A total of 84% (757/907) had an optimal cytoreduction (<1 cm of residual disease), whereas 49% (440/907) had a complete gross resection. The Median follow-up time for the entire cohort was 55 months, and the median overall survival (OS) was 57 months. Twenty percent (183/916) had an OS >10-years. Ten-year OS for pts aged <65 yo with early-stage I/II, stage III, and stage IV ovarian cancer was 48%, 24%, and 11%, respectively. For patients >65 yo, 10-year OS was 22%, 11%, and 4%, respectively. For patients <65 yo, the 10-year CPS for 5-year survivors was: early-stage I/II, 90.0 % (95% CI: 85.4%-94.6%); stage III, 56.8% (95%CI 51.0%-62.7%); stage IV, 38.8% (95% CI: 24.3%- 53.4%). For patients >65y, the 10-year CPS for 5-year survivors was: early-stage I/II, 63.1% (95% CI: 52.6%-73.5%); stage III, 43.8% (95% CI: 31.7%-55.9%); stage IV, 22.5% (95% CI: 6.6%-38.3%). Conclusions: For long-term 5-year survivors with advanced OC, CPS can provide a more representative estimate of future survival than conventional OS ratesl OS. Objectives: To demonstrate the utility of conditional probability of survival (CPS) as a metric in analyzing survival outcomes for women with ovarian cancer. Methods: We analyzed the records of all patients (pts) with newly diagnosed high-grade epithelial ovarian cancer who underwent treatment at our institution from January 2001 to December 2009. Pts lost to follow-up were excluded if they had less than three years of follow-up. CPS was defined as the probability of surviving additional years (y) based on the condition that a patient had already survived at a given time (x): S(x + y)/S(x). Confidence intervals (CIs) were estimated using a variation of Greenwood’s formula. Results: A total of 916 pts met the inclusion criteria. The median age at diagnosis was 60 years (range: 25-95) with 37% (337/916) <65 years old (yo). FIGO stage was as follows: stage I 14% (132/916), stage II 6% (59/916), stage III 57% (519/916), and stage IV 23% (206/916). Histology was high-grade serous in 83% pts (759/916). Among the 907 pts who underwent surgical management, 64% (584/907) had a primary debulking surgery, 16% (143/907) had an interval debulking after neoadjuvant chemotherapy and 20% (180/907) underwent staging. A total of 84% (757/907) had an optimal cytoreduction (<1 cm of residual disease), whereas 49% (440/907) had a complete gross resection. The Median follow-up time for the entire cohort was 55 months, and the median overall survival (OS) was 57 months. Twenty percent (183/916) had an OS >10-years. Ten-year OS for pts aged <65 yo with early-stage I/II, stage III, and stage IV ovarian cancer was 48%, 24%, and 11%, respectively. For patients >65 yo, 10-year OS was 22%, 11%, and 4%, respectively. For patients <65 yo, the 10-year CPS for 5-year survivors was: early-stage I/II, 90.0 % (95% CI: 85.4%-94.6%); stage III, 56.8% (95%CI 51.0%-62.7%); stage IV, 38.8% (95% CI: 24.3%- 53.4%). For patients >65y, the 10-year CPS for 5-year survivors was: early-stage I/II, 63.1% (95% CI: 52.6%-73.5%); stage III, 43.8% (95% CI: 31.7%-55.9%); stage IV, 22.5% (95% CI: 6.6%-38.3%). Conclusions: For long-term 5-year survivors with advanced OC, CPS can provide a more representative estimate of future survival than conventional OS ratesl OS.

Ten-Year Survival and Recurrence Patterns After Three-Field Lymph Node Dissection for Squamous Cell and Adenocarcinoma of the Esophagus.

The aim was to determine the prevalence of metastases to the cervical and recurrent laryngeal cervicothoracic (CT) nodes as well as survival and recurrence patterns after esophagectomy with three-field lymph node dissection (TFD) in patients with predominately adenocarcinoma (AC) of the esophagus. Although esophagectomy with TFD is commonly practiced in Japan and Southeast Asia for squamous cell cancer (SCC) of the esophagus, there are only a handful of reports about its' utilization and survival benefit in North American patients. This is a retrospective case series of patients who had an esophagectomy with TFD. The primary outcomes of interest were the prevalence of nodal metastases to the CT nodes as well as overall survival (OS) and disease-free survival. Secondary outcomes included time to recurrence, recurrence patterns, operative morbidity as well as 30 and 90-day mortality. Two hundred forty-two patients with esophageal cancer (AC: 67%) underwent esophagectomy with TFD. Metastases to the CT nodes were present in 56 patients (23%: AC 20% and SCC 30%). Positive CT nodes were present in 14% of pT1/T2 tumors and 30% of pT3 tumors. For the 56 patients with CT positive nodes, 5-year OS was 25% (AC:16%; SCC:39%). Fifteen of 56 (26.7%) patients with metastases to the CT nodes were alive and disease-free at a minimum of 5 years postoperatively. Ten-year OS was 43% for all patients with SCC and 28% for patients with AC. Metastases to the CT nodes are common in both SCC and AC of the esophagus and may be present in at least 14% of early lesions. Five-year survival is encouraging particularly for patients with esophageal SCC cancer.