Overall Survival In Young Patients Research Articles

Real-world impact on overall survival of oxaliplatin-based adjuvant chemotherapy in older patients with colorectal cancer in Mexico.

61 Background: Colorectal cancer (CRC) is one of the most commonly diagnosed cancer both in Mexico and worldwide, with the peak incidence in patients >65 years. The use of adjuvant chemotherapy (CT) improves the prognosis of high-risk CRC. The benefit from fluorouracil (FU)-based CT across all age groups is not questionable, but the use of oxaliplatin (Ox) is controversial. Methods: Original, retrospective, observational study. Included patients diagnosed with CRC adenocarcinoma treated at the Instituto Nacional de Cancerología México, between 2004 to 2022. Statistical analysis required: X2 and t-test, Kaplan Meier, Log Rank, and Cox Regression. Statistical significance differences were assessed when p was bilaterally <0.05. Results: From 1,238 patients with localized CRC, 275 patients were included in analysis and divided into 2 groups: young (≤ 30 years) (n = 54), and older (≥ 70 years) (n = 221). Most patients were female for both groups (55%). Comorbidities were observed in 2% of young patients and 51% of older patients (p < 0.001). Stages (S) were: II (31%; 39%), and III (59%; 47%). CT was received in 70% of young and 47% of older patients (p = 0.002). Regarding CT regimens, 56% and 21% of young and older patients respectively, had oxaliplatin (p < 0.001), while 21% of young and 32% of older patients did not complete the CT (p = 0.012). Overall survival (OS) analysis was performed considering age and S. S-II median-OS was not reached (NR) for both groups, while S-III median-OS was 170 months (m) for young versus NR for older (p = 0.690). When including CT in OS analysis, patients S-II median-OS was NR for all groups (p = 0.081), while S-III median-OS was 170 m with and 19 m without CT for young versus NR with and 89 m without CT for older, respectively (p = 0.010, 95% CI 0.059-0.123). In S-III older patients, a sub-analysis was performed considering Ox: 10-year-OS was 71% versus 60% for patients treated with and without Ox respectively (p = 0.030, 95% CI 0.25-0.93). In Cox-Regression analysis for patients with clinical stage III, regimen completion (p = 0.004; HR 0.38, 95% CI 0.201-0.745) and Ox (p = 0.022; HR 0.423, 95% CI 0.203-0.881) remained as predictor factors of OS. Conclusions: There are no studies which compare the administration of CT between young and older patients or the description of these populations in Mexico. Young patients are more likely to receive CT with Ox assumingly due to the lack of comorbidities and life expectancy. The benefit of CT on OS in young patients is not in question. An increase in OS was found in older patients who received CT with Ox, but a higher percentage of treatment discontinuation secondary to toxicity. As recommended by the literature, its essential to integrate assessment in older patients to determine which patients will benefit from complete CT regimens to increase their OS, apart from their chronological age.

Characteristics and outcomes of children, adolescents and young adults with relapsed/refractory non-hodgkin lymphoma undergoing autologous stem cell transplant

BackgroundThere is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT).MethodsPatients aged 0–39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed.ResultsTwo hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6–39) years. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) (44%), T-NHL (19%) and primary mediastinal B-Cell lymphoma (PMBCL) (19%). Younger patients (age ≤ 25) had lower incidence of DLBCL and higher incidence of PMBCL and T-NHL compared to older patients (age > 25) (P = 0.02). None of the younger patients had double hit (DH)/double expressor (DE) DLBCL, compared to 14 patients in the older age group (18%, P = 0.07). Considering the three main aggressive NHL subtypes (DLBCL, PMBCL and T-NHL), younger patients had numerically better 15-year post-transplant progression free survival (PFS) (67% vs. 54%) and overall survival (OS) (71% vs. 62%) compared to older patients, yet these differences did not reach statistical significance (P = 0.19 and P = 0.24, respectively). In multivariate analysis, not achieving a CR prior to ASCT was independently predictive of worse PFS [partial remission (PR) (HR, 3.9); stable disease (SD) (HR, 18.0), P = 0.03] and of worse OS [PR (HR, 4.2), SD (HR, 6.5) and progressive disease (HR, 4.7), P < 0.0001]. DH/DE status was an independent adverse predictor of PFS in multivariate analysis (HR 5.8, p = 0.03).Ten patients (4.5%) (all aged > 25 years) developed second primary malignancies (SPM), at a median of 34.4 (range, 1.0–196.6) months after ASCT, and SPM was the cause of death in five (50%) of them.ConclusionsCAYA NHL patients aged ≤ 25 years who received ASCT presented a distinct NHL histology as compared to older CAYA patients, and none in this younger age group had DH/DE DLBCL. We observed a trend towards improved PFS and OS in younger patients. Disease status at ASCT was predictive of both PFS and OS. DH/DE status was an adverse predictor of PFS.

Development and validation of a nomogram for predicting overall survival in patients with early-onset endometrial cancer

BackgroundThis study aimed to investigate the differences in the clinicopathological characteristics of younger and older patients with endometrial cancer (EC) and develop a nomogram to assess the prognosis of early onset EC in terms of overall survival.MethodsPatients diagnosed with EC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were selected. Clinicopathological characteristics were compared between younger and older patients, and survival analysis was performed for both groups. Prognostic factors affecting overall survival in young patients with EC were identified using Cox regression. A nomogram was created and internal validation was performed using the consistency index, decision curve analysis, receiver operating characteristic curves, and calibration curves. External validation used data from 70 patients with early onset EC. Finally, Kaplan-Meier curves were plotted to compare survival outcomes across the risk subgroups.ResultsA total of 1042 young patients and 12,991 older patients were included in this study. Younger patients were divided into training (732) and validation (310) cohorts in a 7:3 ratio. Cox regression analysis identified age, tumorsize, grade, FIGO stage(International Federation of Gynecology and Obstetrics) and surgery as independent risk factors for overall survival, and a nomogram was constructed based on these factors. Internal and external validations demonstrated the good predictive power of the nomogram. In particular, the C-index for the overall survival nomogram was 0.832 [95% confidence interval (0.797–0.844)] in the training cohort and 0.839 (0.810–0.868) in the internal validation cohort. The differences in the Kaplan-Meier curves between the different risk subgroups were statistically significant.ConclusionsIn this study, a nomogram for predicting overall survival of patients with early onset endometrial cancer based on the SEER database was developed to help assess the prognosis of patients and guide clinical treatment.

The Prognostic Impact of Body Composition Assessment By Computed Tomography in Adult Patients with Newly Diagnosed Acute Lymphoblastic Leukemia

The Prognostic Impact of Body Composition Assessment By Computed Tomography in Adult Patients with Newly Diagnosed Acute Lymphoblastic Leukemia

A randomized comparison of CPX-351 and FLAG-Ida in adverse karyotype AML and high-risk MDS: the UK NCRI AML19 trial

AbstractLiposomal daunorubicin and cytarabine (CPX-351) improved overall survival (OS) compared with 7+3 chemotherapy in older patients with secondary acute myeloid leukemia (AML); to date, there have been no randomized studies in younger patients. The high-risk cohort of the UK NCRI AML19 trial (ISRCTN78449203) compared CPX-351 with FLAG-Ida in younger adults with newly diagnosed adverse cytogenetic AML or high-risk myelodysplastic syndromes (MDS). A total of 189 patients were randomized (median age, 56 years). Per clinical criteria, 49% of patients had de novo AML, 20% had secondary AML, and 30% had high-risk MDS. MDS-related cytogenetics were present in 73% of the patients, with a complex karyotype in 49%. TP53 was the most common mutated gene, in 43%. Myelodysplasia-related gene mutations were present in 75 (44%) patients. The overall response rate (CR + CRi) after course 2 was 64% and 76% for CPX-351 and FLAG-Ida, respectively. There was no difference in OS (13.3 months vs 11.4 months) or event-free survival in multivariable analysis. However, relapse-free survival was significantly longer with CPX-351 (median 22.1 vs 8.35 months). There was no difference between the treatment arms in patients with clinically defined secondary AML or those with MDS-related cytogenetic abnormalities; however, an exploratory subgroup of patients with MDS-related gene mutations had significantly longer OS with CPX-351 (median 38.4 vs 16.3 months). In conclusion, the OS of younger patients with adverse risk AML/MDS was not significantly different between CPX-351 and FLAG-Ida.

Abstract GS5-01: Addition of platinum to sequential taxane-anthracycline neoadjuvant chemotherapy in patients with triple-negative breast cancer: A phase III randomized controlled trial

Abstract Background: Despite several studies, the impact of adding platinum on long-term outcomes in triple-negative breast cancer (TNBC) has not been definitively established. We conducted a single-centre randomized phase III trial to evaluate the efficacy and toxicity of adding platinum to standard neoadjuvant chemotherapy in these patients. Methods: Patients with histopathological diagnosis of TNBC without evidence of distant metastases who were planned to be treated with neoadjuvant chemotherapy (NACT) were randomized to experimental or control arms after stratification by menopausal status (premenopausal or perimenopausal, and postmenopausal) and stage [operable breast cancer (OBC, clinical T1-3, N0-1, M0), and locally advanced breast cancer (LABC, cT4 or N2-3, M0)]. NACT in control arm included paclitaxel 100 mg/m2 once per week for 8 weeks followed by doxorubicin (60 mg/m2) or epirubicin (90 mg/m2) plus cyclophosphamide (600 mg/m2) once every 21 days for 4 cycles while in experimental arm carboplatin (area-under-curve 2) was added once per week for 8 weeks with paclitaxel. After NACT patients received standard surgery for primary tumor and axillary lymph nodes (LN) followed by radiotherapy. The primary endpoint was disease-free survival (DFS) and the secondary endpoints were overall survival (OS), pathological complete response (pCR, absence of invasive cancer from breast and LN), and toxicity. Results: Between April 2010 and January 2020, 720 (355 control, 365 experimental) patients with a median age of 46 (25-69) years [&amp;lt; 50 years, 502 (69.7%), premenopausal 418 (58.2%)], were included in the study, of whom 285 (39.6%) had OBC and 435 (60.4%) had LABC, with a median clinical tumor size of 6.0 (1.2- 20.0) cm. At a median follow-up of 67.6 (18.9-142.2) months, in the experimental and control arms, the 5-year DFS were 70.6% (95% CI 65.7-75.5%) and 64.5% (95% CI 59.4-69.6%), respectively (HR 0.79, 95% CI 0.61-1.02, p=0.073), 5-year OS were 74.0 (95% CI 69.3-78.7%) and 66.7% (95% CI 61.6-71.8%), respectively (HR 0.75, 95% CI 0.57-0.98, p=0.034), and pCR were 55.2% (95% CI 49.7-69.5%) and 41.5% (95% CI 36.2-47.0%), respectively (p=0.0004). In subgroup analyses, the benefit of carboplatin was confined to patient’s &amp;lt; 50 years, with significant interaction between treatment and age. In women &amp;lt; 50 years of age, in experimental versus control arms, 5-year DFS and OS were 74.5% vs 62.3% (p=0.003, interaction p=0.003) and 76.8% vs 65.7% (p=0.003, interaction p=0.004), respectively. Addition of carboplatin had a significant beneficial impact on OS after adjusting for baseline clinical tumor size and age in a Cox model (HR 0.75, 95% CI 0.58-0.98, p=0.038). In experimental and control arms, numbers of patients with any grade &amp;gt;/=3 toxicity were 140 (38.5%) and 107/355 (30.14%), respectively, (p=0.02), grade &amp;gt;/=3 neutropenia were 2/364 (0.55%) and 1/355 (0.28%), respectively, grade &amp;gt;/=3 thrombocytopenia were 1/364 (0.27%) and 0 (0%), respectively, and febrile neutropenia were 26/364 (7.14%%) and 18/355 (5.07%), respectively (p=0.25). Conclusions: This study, to our knowledge the largest reported trial of neoadjuvant platinum in TNBC thus far, suggests that addition of carboplatin to sequential taxane-anthracycline neoadjuvant chemotherapy results in substantial and clinically meaningful improvement in disease-free and overall survival in young patients with TNBC and should be the standard of care in these patients. Citation Format: Sudeep Gupta, Nita S. Nair, Rohini Hawaldar, Vaibhav Vanmali, Vani Parmar, Seema Gulia, Jaya Ghosh, Shalaka Joshi, Rajiv Sarin, Tabassum Wadasadawala, Tejal Panhale, Sangeeta Desai, Tanuja Shet, Asawari Patil, Garvit Chitkara, Sushmita Rath, Jyoti Bajpai, Meenakshi Thakkur, Rajendra Badwe. Addition of platinum to sequential taxane-anthracycline neoadjuvant chemotherapy in patients with triple-negative breast cancer: A phase III randomized controlled trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS5-01.

Disease-free survival does not differ according to fertility preservation technique for young women with breast cancer

To study whether fertility preservation strategies using ovarian stimulation or without using it impact long-term disease-free survival of patients with breast cancer. Retrospective bicentric cohort study. Two university hospitals. In this study, 740 women with breast cancer, aged 18-43 years, who received primary fertility preservation between 2013 and 2019 after a diagnosis of localized breast cancer were included. Overall, 328 patients underwent at least 1 ovarian stimulation cycle (STIM group) and 412 had a technique without hormonal administration (no STIM group). Disease-free survival and overall survival up to May 2021 were compared between the 2 groups by log-rank test. Cox proportional-hazard regression model was used for multivariable analyses. Out of the 740 women who underwent fertility preservation, follow-up data were available for 269 women in the STIM group (82%) and 330 (80%) in the no STIM group. Kaplan-Meier estimates of disease-free survival at 4 years were 87.9% (82.8%-92.2%) and 83.1% (78.4%-87.3%) in the STIM and no STIM groups, respectively. After adjustment on prognostic parameters, no significant difference in breast cancer recurrence rate was observed between the STIM and no STIM groups (hazard ratios, 0.83 [0.64-1.08]). Kaplan-Meier estimate of overall survival at 4 years was 97.6% (95.3%-99.2%) and 93.6% (90.9%-95.9%) in the STIM and no STIM groups, respectively. Overall survival was higher in the STIM group than no STIM group (log-rank test). After adjustment on prognostic parameters, the risk of death remained significantly lower in the STIM group (Hazard Ratio, 0.55 [0.35-0.85]). In our cohort, STIM for fertility preservation in breast cancer did not significantly impact disease-free survival but was associated with higher overall survival. The disease-free survival and overall survival of young patients with breast cancer were not impacted by fertility preservation techniques irrespective of the timing of chemotherapy (neoadjuvant or adjuvant) and the use of ovarian stimulation. Nevertheless, because death and recurrence were rare events, these results should be taken with caution.

Rituximab Maintenance (RM) after First-Line (1L) Treatment Is Associated with a Lower Risk of Early-POD in Patients with Mantle Cell Lymphoma (MCL)

Background RM after 1L immunochemotherapy has improved the Progression-Free Survival (PFS) and Overall Survival (OS) in MCL in phase III clinical trials and in real-life patients. Early progression/relapse (E-POD) after 1L has been significantly associated with a shorter OS in younger patients with MCL after intensive 1L and autologous stem-cell transplantation (ASCT), although these patients did not receive RM (Visco et al, BJH 2019). The aim of our study was to analyze the impact of the use of RM on the risk of early-POD in a real-life cohort of patients with MCL. Methods We retrospectively reviewed all patients diagnosed with MCL between January 2000 and December 2021 at 6 tertiary centers. Only patients receiving 1L at diagnosis and achieving complete (CR) or partial response (PR) were eligible for maintenance and therefore included in this analysis. Patients were categorized as "RM” if they had received RM after 1L or as "non-RM” if they had not. Relapse/progression after 1L occurring before or after the first 24 months (m) from diagnosis was considered early or E-POD and late or L-POD, respectively (Visco et al, BJH 2019). Patients not relapsing after 1L were considered L-POD only if their follow-up time (FU) from diagnosis was 24 months or longer. Patient's characteristics, biological risk factors at diagnosis, as well as the type of 1L were recorded (intensive immunochemotherapy with high-dose cytarabine -HiDAC- or standard immunochemotherapy without HiDAC -non-HiDAC-), with or without ASCT consolidation. The duration of response (DOR) after 1L, PFS and OS were also analyzed for all patients. Statistical analyses were performed with the R-4.1.0 software. Univariate logistic regression was carried out to study the association between E-POD and maintenance. Survival analysis (DOR, PFS and OS) were calculated using the Kaplan-Meier method and the univariate Cox was used for statistical comparison. Results Out of 212 patients attaining CR or PR after 1L, 87 (41%) received maintenance therapy (RM group) whereas 125 patients (59%) did not (non-RM group). The RM regimens administered were: rituximab monotherapy (R)/8 weeks (wk) x 2 years (N=41), R/8 wk x 3 years (N=27) and other R-based regimens (with BTK inhibitors, N=7; other R schedules, N=12). Except for a higher percentage of patients older >65 years at diagnosis in the RM group (51.7% RM vs. 37.6% non-RM, p=0.042), the rest of baseline characteristics were well balanced between the two groups (Table 1). Regarding 1L, more patients in the full cohort had received a non-HiDAC regimen [120 pts (56.6%) non-HiDAC vs. 92 pts (43.4%) HiDAC], but the proportion of patients receiving RM was similar after both types of 1L. Only 22 out of the 87 patients in the RM group (25.3%) had undergone previous ASCT consolidation (Table 1). With a median follow-up of 72.8 months (51.52 m and 92.65 m in the RM and non-RM groups, respectively), median PFS was 44.39 m (36.11-55.46), with a significant advantage for the RM group (61.04 m vs. 32.82 m, HR=1.7 [1.15-2.51], p=0.01) (Figure 1). Moreover, median DOR was 30.03 m (26.02-42.94), also significantly longer in the RM group (53.88 m vs. 24.21 m, HR=1.61 [1.12-2.3], p=0.01). Median OS was 12.18 yrs (8.66-NR) in the full cohort, with no significant differences between the two groups (14.03 yrs vs. 11.48 yrs, HR=1.34 [0.74-2.45], p=0.34). Regarding POD24, a statistically significant association was observed between not receiving RM and early-POD: 49 patients (40.5%) were E-POD in the non-RM group compared with only 19 (24.4%) in the RM group (OR=2.11 [1.14-4.04], p=0.020) (Table 1). Conclusions Only 41% of our real-life cohort received RM despite it being considered a safe and effective strategy for MCL patients. In line with previous studies, in our series RM after 1L is associated with a significant advantage in terms of PFS and DOR, although it did not have impact on OS. In our cohort, RM is significantly associated with a lower risk of early-POD, in all age groups and regardless of the 1L induction strategy, therefore confirming the benefit of this strategy in the management and outcomes of MCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Impaired Overall Survival in Young Patients With Acute Myeloid Leukemia and Variants in Genes Predisposing for Myeloid Malignancies.

Impaired Overall Survival in Young Patients With Acute Myeloid Leukemia and Variants in Genes Predisposing for Myeloid Malignancies.

Molecular heterogeneity and analysis of the long-term survival of patients with gastrointestinal stromal tumors

Introduction. Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract the character diagnostic feature of which is CD117 (KIT) expression. GISTs are clinically diverse and have different genetic alterations that may have predictive and prognostic significance.Aim – the study of clinical, morphological and genetic features of GISTs to assess the overall survival (OS) of patients with various profiles of genetic disorders for elucidation the factors contributing to prognosis.Materials and methods. A total 244 GIST patients who received combined treatment were enrolled in the study and their clinical characteristics and mutational status of KIT, PDGFRA, BRAF were analyzed. SDH-deficient GISTs were detected using IHC-analysis of SDHB expression.Results. Stromal tumors developed in stomach (50 %), small intestine (37.7 %), colon or rectum (8.6 %), esophagus (0.4 %) and extraorganically (EGIST, 5.7 %). Overall survival correlated with gastric site (p = 0.005), tumor size &lt;10 cm (p = 0,0001) and mitotic count HPF&lt; 10 / 50 (p = 0.007). KIT mutations were found in 168 (68.9 %) and PDGFRA – in 31 (12.1 %) of GISTs, 14 novel mutations were detected. Mutations in KIT exon 11 were found in 140 (57.4 %) tumors, 10-year OS, 51 %, median 124 months. Patients with deletions had lower OS than patients with substitutions or duplications in KIT exon 11 (p = 0,023). The lowest OS was in patients with primary mutations in KIT exons 13 or 17 (median 28 months) and duplications in KIT exon 9 (median 71 months). There was a low OS of young patients with homozygous KIT mutations, mutations that begin in intron and two simultaneous KIT mutations. GISTs with PDGFRA mutations were located in stomach and had no metastases, 10-year OS, 63 %, median 175 months. KIT / PDGFRA mutations were not observed in 45 (18.4 %) patients (wild-type GIST), 10-year OS, 59 %, median 250 months. Wild-type GISTs with BRAF, NF1 mutations and SDH deficiency were detected. The better OS was demonstrated by patients with BRAFV600E (10-year ОS, 84 %, median 97 months) and SDH deficiency (10-year and 15-year OS, 82 %).Conclusion. Genetic analysis is necessary to clarify GIST prognosis and predict the effectiveness of targeted therapy. The clinical, morphological and genetic diversity of GISTs was confirmed. Wild-type GISTs with BRAF mutations and SDHdeficiency were identified in the Russian population for the first time. The long-term 10- и 15-year OS of GIST patients were evaluated.

P-242 Colorectal cancer in young adults: Experience of the medical oncology department of Fez

The recent rise of young individuals under age 50 with colorectal cancer (CRC) is a startling trend in need of greater focus and research. The rapid increase in incidence rates among young people could result from generational differences in diet, environmental exposures and lifestyle factors. The aim of this study is to describe the epidemiological changes as well as the differences in the clinicopathologic, molecular characteristics of young patients. This is a retrospective study of young patient with colorectal cancer aged < 45 and treated at the medical oncology department of Fez over a period from December 2009 to September 2020. The Kaplan Meier method was used to estimate the median survival. - 158 (24% ) patients were young, of whom 16% had family history, and 11% were obese. Mucinous adenocarcinoma was present in 53%. 46% were at the metastatic stage, of which 80% had a poorly differentiated character. At stage II, MSI status was present in 62%. The mutated RAS status was 40%.51% received trichemotherapy versus 49% bichemotherapy. The preferential site was in 52% the liver, 30% the lung and the bone in 16%. However, young patients diagnosed with early-stage tumors had a significantly better prognosis compared to early-stage tumors in the older age group. The majority of young patients with colorectal cancer often receive more aggressive treatment regimens than their older counterparts. Median overall survival in young patients was 16 months. Early-onset colorectal carcinoma are a distinct clinical group characterized by poor cellular differentiation and aggressive evolution. Several factors may well explain this apparent epidemic among young people, namely and emerging lifestyle issues such as obesity, lack of exercise and dietary factors.

Massive myxopapillary ependymoma of the gluteal cleft.

A 19-year-old male presented with a 2-year history of a progressively enlarging sacrococcygeal mass. Despite the significant size of the mass resulting in disfigurement and difficulty maintaining hygiene, he presented after the development of ulceration of the overlying skin and associated bleeding (Fig. 1). He denied any associated bladder or bowel changes, and had a normal lower limb neurological examination. He had no significant past medical history with no regular medications. Further investigation included a pelvic Magnetic Resonance Image (MRI) (Fig. 2) which showed an 11.4 × 9.9 × 10.3 cm lesion arising from the coccyx extending into the subcutaneous soft tissues of the gluteal cleft, characterized by multiple internal septations, marked T2 hyperintensity and avid Gadolinium enhancement. Histological examination of an image-guided core biopsy was suggestive of a myxopapillary ependymoma. A resection of the sacrococcygeal tumour was performed under general anaesthesia in the prone position. Macroscopically clear margins were achieved with en bloc resection of gluteal muscle, fascia and the coccyx. The wound was closed primarily with interrupted sutures and a suction drain to the resection cavity. Microscopic pathological assessment of the tumour revealed cuboidal tumour cells radially arranged in a papillary manner around vascularized stromal cores, separated by abundant myxoid matrix. The tumour extended beyond the deep fascia and into the marrow of the coccyx. Lymphovascular and perineural invasion were present. The immunocytochemical assessment demonstrated expression of the glial fibrillary acidic protein, but was negative for CK5/6, cytokeratin and SOX10, consistent with the preoperative diagnosis of myxopapillary ependymoma and differentiating the lesion from the more common chordoma. Resection margins were microscopically clear. The patient had an uncomplicated post-operative recovery and was discharged home on Day 7. At 1-year follow-up, he remains well, with no clinical or radiological evidence of recurrent disease. A myxopapillary ependymoma is a slow-growing histological variant of ependymoma that commonly originate within the filum terminale or conus medullaris in the lumbosacral region.1, 2 Virchow3 first identified ependymal tumours in 1865; however, it was not until 1935 when Kernohan and Fletcher-Kerohan4 sub-classified a selection of these tumours as myxopapillary ependymomas. They are currently classified according to the World Health Organization Classification of Tumours of the Nervous System as Grade 1 gliomas.5 Myxopapillary ependymomas are rare, with an incidence of 1 per million person-years.6 The average age of diagnosis of these tumours is 36, however, tumours found in paediatric patients are generally more aggressive and are more likely to metastasise.7 Grossly, these tumours are usually small encapsulated masses with gelatinous interiors. Microscopically, the characteristic features of the tumours are a pseudo-papillary pattern of cuboidal tumour cells around a vascular stromal core that undergoes mucinous degeneration.8 Though considered to have indolent biological behaviour, up to 31.7% of patients will experience disease recurrence. Of these patients, most experience local recurrence (84.5%), however over one-third of patients have non-local disease involving the distant spine and/or brain.8 Surgical resection is the mainstay treatment modality for myxopapillary ependymoma. The role of adjuvant radiotherapy is controversial, but may improve local recurrence, progression-free and overall survival in younger patients, particularly in the setting of subtotal resection.8, 9 Younger age, subtotal or piecemeal resection and larger tumour size (>2 cm) confer poorer prognosis. The prognostic significance of massive tumour size such as in the case presented here remains uncertain due to its rarity, and close clinical and radiological surveillance is warranted. Open access publishing facilitated by University of New South Wales, as part of the Wiley - University of New South Wales agreement via the Council of Australian University Librarians. BJ completed the initial draft. SF, DD, MN & PC were involved in the drafting and editing of the manuscript. All authors viewed the manuscript before submission.

Efficacy of anti-epidermal growth factor receptor agents in patients with RAS wild-type metastatic colorectal cancer ≥ 70 years

PurposeColorectal cancer (CRC) affects many older adults. We investigated the efficacy and safety of adding anti-epidermal growth factor receptor (EGFR) agents to doublet chemotherapy (DC) in older patients. MethodsPatients with RAS wild-type (WT) metastatic CRC (mCRC) receiving first-line DC + anti-EGFR (n = 1191) or DC alone (n = 729) from seven trials in the Aide de Recherche en Cancerologie Digestive database were included. The prognostic and predictive effects of age were investigated. Progression-free and overall survival (OS) were evaluated between age groups (≥70 vs <70) for DC + anti-EGFR. In addition, outcomes were compared between DC+/-anti-EGFR within age groups in three trials with a DC alone arm. Subsequently, the same analysis was conducted for left-sided tumours. Adverse events grade ≥3 (G3+) were compared between age groups. ResultsOlder (vs younger) patients receiving DC + anti-EGFR had similar progression-free survival (PFS) (8.7 vs 10.3 months; hazard ratio (HR) = 1.20 [0.96–1.49];p = 0.107) but inferior OS (21.3 vs 26.3; HR = 1.36 [1.08–1.72];p = 0.011). DC + anti-EGFR (vs DC alone) improved OS (23.9 vs 20.3; HR = 0.82 [0.70–0.95];p = 0.008) and PFS (11.2 vs 8.9; HR = 0.70 [0.60–0.82];p < 0.001) in younger but not older patients: OS (24.7 vs 17.6; HR [95% confidence interval {CI}] = 0.77 [0.58–1.04];p = 0.092) and PFS (9.1 vs 8.7; HR [95% CI] = 0.85[0.63–1.15];p = 0.287). In left-sided ‘only’ tumours, the following outcomes for older (vs younger) patients were observed. For DC + anti-EGFR, PFS 9 versus 11.2 months; HR1.10 (95% CI 0.83–1.46); p = 0.52, OS 25.6 vs 30.3 HR 1.32 (95% CI 0.97–1.79), p = 0.086. For DC + anti-EGFR (vs DC alone), PFS and OS for younger patients were 11.9 vs 9.2 months HR 0.60 (95% CI 0.47–0.78) p < 0.001 and 24.1 versus 23.3 months HR 0.84 (95% CI 0.67–1.04), respectively. For older patients, PFS and OS were 13.1 versus 8.5 months, HR 0.51 (95% CI, 0.28–0.93), P = 0.027 and 26.3 versus 16.5 months HR 0.49 (95% CI, 0.28–0.85), respectively. There was no significant difference in toxicity among different age groups. ConclusionsOlder (vs younger) patients with mCRC RAS WT patients had comparable toxicity and efficacy with the addition of anti-EGFR agents to chemotherapy.

Long-Term Outcomes of Total Body Irradiation Plus Cyclophosphamide Versus Busulfan Plus Cyclophosphamide As Conditioning Regimen for Acute Lymphoblastic Leukemia: A Comparative Study

Introduction: Total body irradiation-Cyclophosphamide (TBI-Cy) and Busulfan-Cyclophosphamide (Bu-Cy) are the most commonly used conditioning regimens in allogeneic hematopoietic stem cell transplantation (allo-HCT) for acute lymphoblastic leukemia (ALL). TBI-based conditioning regimens may have a better antitumor effect at sanctuary cites compared to chemotherapy regimens. However, some controversy still remains concerning the role of TBI in adult ALL. Therefore, we aimed to retrospectively investigate long-term treatment outcomes of ALL patients post allo-HCT and identify prognostic factors and the impact of the conditioning.Methods: We enrolled consecutive patients with ALL who underwent alloHCT from 1990 to 2016 in our center, following a TBI- or a Busulfan (Bu)-based conditioning regimen. TBI at 14.4Gy was divided at 6 fractions over 3 days and Bu (mainly oral) at 4mg/kg/day. Both regimens included 120mg/kg Cy. Graft source was mainly mobilized peripheral blood stem cells.Results: We studied 151 ALL (114 B-ALL, 35 T-ALL and 2 biphenotypic) patients aged 28±12 years, transplanted in CR1 (60), other CR (33) or relapsed/refractory disease (58) from sibling (87), HLA matched (42) or mis-matched (17) unrelated and alternative donors (5). TBI-based conditioning was administered in 84, whereas non-TBI in 67. No differences were observed in baseline characteristics, except for disease phase, disease risk index (DRI) and graft source. The majority of non-TBI patients had relapsed/refractory disease at transplant (50.7% versus 28.6% in TBI-conditioning, p=0.043) and subsequently significantly higher DRI (p=0.025). Furthermore, bone marrow was the graft source in significantly higher number of non-TBI patients (28.4% versus 8.3% in the TBI group, p=0.001).With a follow-up of 19.0 (0.5-170.5) in TBI and 14.5 (1.2-319.1) months in the non-TBI group, there was no difference in the incidence of acute (Grade 2-4) or chronic GVHD, thrombotic microangiopathy, bacterial or fungal infections. Only viral infections were significantly increased in the non-TBI group (59% versus 41% in the TBI group, p=0.03). Therefore, there was no significant difference in the cumulative incidence (CI) of treatment-related mortality (5-year CI of 24.1% in non-TBI versus 27.7% in the TBI group, p=0.678) or relapse mortality (5-year CI of 29.2% in non-TBI versus 37.1% in the TBI group, p=0.283).Overall survival (OS) was similar in the TBI and non-TBI group (5-year 46.7% compared to 35.8%, p=0.201). In the multivariate analysis, unfavorable pre-transplant predictors of OS were age (p=0.024), higher disease risk index (DRI) (p=0.007) and female to male donor (p=0.006). Disease-free survival (DFS) was similar in the TBI and non-TBI group (5-year 47.1% compared to 35.4%, p=0.134), with age, higher DRI and female to male donor being unfavorable predictors. When the analysis was limited to patients transplanted in CR1 (40 in the TBI versus 20 in the non-TBI group), there were also no significant differences.Interestingly, age predicted OS and DFS only in the TBI group. TBI patients younger than 40 years had significantly high OS (55.1%, p=0.023) and DFS (55.5%, p=0.02) versus the older ones. Older TBI patients had higher TRM (43.3% versus 20.1%, p=0.135) and relapse mortality (45.8 versus 24.7, p=0.238) that did not reach levels of statistical significance. However, the same was not true for the non-TBI group (p=0.233 for DFS, p=0.326 for OS).Conclusion: In our retrospective data of the last 3 decades, the type of conditioning regimen did not influence the outcome of transplantation. Based on our results, high dose TBI is a feasible conditioning in terms of a prolonged DFS and OS for younger patients and seems an efficient tool to cure high-risk ALL in CR1. It should be kept in mind that intravenous BU is also used with stable pharmacokinetics. Since our data were not powered to appraise superiority of one regimen in terms of efficacy and toxicity, the choice between TBI or Bu conditioning regimens is still under consideration. Treatment is complex for adult ALL patients and remains a field of debate and a challenge for prospective studies in the future. DisclosuresGavriilaki:European Hematology Association: Research Funding.

Improved overall survival for patients with early-onset pancreatic ductal adenocarcinoma.

379 Background: The median age of diagnosis of pancreatic ductal adenocarcinomas (PDAC) is 70 years. Only about 20% of patients are diagnosed prior to the age of 60. We sought to identify clinical characteristics and outcomes of patients with early-onset PDAC as compared to later-onset PDAC. Methods: We identified histologically confirmed cases of pancreatic adenocarcinoma with information about age and overall survival (OS) diagnosed between 2004 and 2016 from the National Cancer Database (NCDB). Differences in demographic, disease and treatment characteristics and socioeconomic factors between younger and older patients were assessed by Chi-square test. The effect of age, race, insurance status, community median income and community educational attainment on overall survival (OS) were assessed using log rank test. Results: Of 321,896 patients who met inclusion criteria, 71,263 (22%) were younger than 60 years and 250,633 were 60 years of age or older at diagnosis. Median OS for younger patients was 9.5 months, compared to 5.6 months for older patients ( p&lt; 0.0001). Younger patients were more likely to be diagnosed with stage IV disease (47.8% vs 43.4%), to be Black (16.1% vs 10.7%) or Hispanic (6.4% vs 4.5%), have a Charlson-Deyo comorbidity index of 0 (73.5% vs 63.3%), have private insurance (65.1% vs 20.5%), and receive treatment at academic centers (45.9% vs 40.9) (all p&lt; 0.0001). Younger patients were also more likely to receive surgery (26.2% vs 19.5%), radiation (23.0% vs 15.9%), and chemotherapy (65.9% vs 46.7%) (all p&lt; 0.0001). Conclusions: Survival for patients with early-onset PDAC is significantly better than older patients despite more patients being diagnosed with stage IV disease. This may be attributable to younger patients having less comorbidities and receiving more treatment. Concerningly, Black and Hispanic patients make up a larger proportion of younger patients with PDAC, and further work is needed to investigate these differences and underlying causes.

Survival Improvement over Time of 960 s-AML Patients Included in 13 EORTC-GIMEMA-HOVON Trials.

Simple SummarySecondary acute myeloid leukemia (s-AML) refers to the development of AML following myelodysplatic syndrome or other hematological malignancies, or after a solid tumors, or nonmalignant diseases or following exposure to environmental or occupational carcinogens. Here, we report data from 960 s-AML patients who were treated in 13 EORTC collaborative trials conducted between May 1986 and January 2008. The main aims of our study were (1) to assess whether overall survival of s-AML patients improved over time, (2) to identify initial disease features associated with overall survival. We observed that overall survival of younger patients improved over the years, in parallel with introduction of high-dose cytarabine in induction remission chemotherapy. This suggests that this strategy should be further investigated in younger patients with s-AML. Furthermore, this study confirmed that the sAML patients having adverse cytogenetic risk features and those with high white blood cells at diagnosis had a dismal survival, regardless of their age group.We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A; n = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B; n = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C; n = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively. Among patients ≤60 years and classified in the cohorts A or B (n = 367), the 5-year overall survival (OS) rate was 28%. There was a systematic improvement in the 5-year OS rate over three time periods (p < 0.001): 7.7% (95% CI: 1.3–21.7%) for patients treated before 1990 (period 1: n = 26), 23.3% (95% CI: 17.1–30.0%) for those treated between 1990 and 2000 (period 2: n = 188) and 36.5% (95% CI: 28.7–44.3%) for those treated in 2000 or later (period 3: n = 153). In multivariate analysis, male gender (HR = 1.39; p = 0.01), WBC ≥ 25 × 109/L (HR = 2.00; p < 0.0001), age 46-60 years (HR = 1.65; p < 0.001) and poor-risk cytogenetics (HR = 2.17; p < 0.0001) were independently associated with shorter OS, while being treated during period 2 (HR = 0.50, p = 0.003) or period 3 (HR = 0.43; p = 0.0008). Having received high-dose cytarabine (HD-AraC) (n = 48) in the induction chemotherapy (HR = 0.54, p = 0.012) was associated with a longer OS. In contrast, among patients >60 years of age (n = 502), the OS was dismal, and there was no improvement over time.

Comparison of Outcomes Between McKeown and Sweet Esophagectomy in the Elderly Patients for Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Analysis.

The aim of this study was to compare the perioperative outcomes and long-term survival rates of the McKeown and Sweet procedures in patients with esophageal cancer younger than 70 years or older than 70 years. A total of 1432 consecutive patients with esophageal squamous cell carcinoma (ESCC) who received surgery at Sun Yat-sen University Cancer Center from January 2009 to October 2012 were analyzed. Propensity score matching was used to balance the clinical characteristics of the patients who underwent different surgical approaches, and 275 and 71 paired cases were matched among those younger and older than 70 years, respectively. The prognosis and postoperative outcomes were compared between the McKeown and the Sweet esophagectomy. For patients younger than 70 years, those who underwent the McKeown procedure had better overall survival (OS) than those in the Sweet group (log rank = 4.467; P = .035). However, no significant difference in disease-free survival and OS was observed between two approaches for the elderly patients (log rank = 1.562; P = .211 and log rank = 0.668; P = .414, respectively). Cox regression analysis revealed that McKeown approach was a positive prognostic factor compared to the Sweet approach for patients younger than 70 years in univariable analysis (HR = 0.790; 95% CI, 0.625-0.997; P = .047), whereas the surgical approach was not significantly related to the prognosis in the elderly patients. For patients older than 70 years, the occurrence of anastomotic fistula increased in those who underwent the McKeown procedure (23.9% vs 11.3%, P = .038, for the McKeown and Sweet esophagectomy, respectively). The McKeown approach increases the OS in younger patients with ESCC. However, for patients older than 70 years, the Sweet approach was proven to be an effective therapy, given the better perioperative outcomes and similar long-term survival compared with patients in the McKeown group.

Impact of prior cancer history on the overall survival of younger patients with lung cancer

BackgroundPatients with a history of prior cancer are frequently excluded from cancer trials. Previous studies indicated that prior cancer does not adversely impact clinical outcomes for patients with lung cancer older than 65 years. However, it remains unknown whether these results are applicable to patients with lung cancer aged younger than 65 years old. The study aimed to investigate the impact of prior cancer history on younger patients with lung cancer.MethodsWe identified younger patients with lung cancer (<65 years) diagnosed between 2004 and 2009 in the Surveillance, Epidemiology, and End Results database. Propensity score matching was performed to balance differences in baseline characteristics between groups. Kaplan-Meier method and the Cox proportional hazards model were used to evaluate the impact of prior cancer on overall survival (OS).ResultsAmong 103 370 eligible patients with lung cancer, 15.18% had a history of prior cancer. Lung and bronchus (25.83%), breast (14.13%), prostate (8.85%) and cervix uteri (4.74%) were the most common prior cancer types. Of prior cancers, 61.56% are localised and regional stages. More than 67.98% of prior cancers were diagnosed within 5 years of the index lung cancer diagnosis. The median times of diagnosis for prior cancers were 38 months. Patients with prior cancer had the same/non-inferior OS as that of patients without a prior cancer diagnosis (propensity score-adjusted HR=1.01, 95% CI=0.99 to 1.04, p=0.324). Subgroup analyses stratified by timing of prior cancer displayed almost the same tendency (p>0.05). Interestingly, early-stage patients with a history of prior cancer had adverse survival curves (p<0.05). Advanced-stage patients with prior cancer had non-inferior survival (p>0.05).ConclusionsA prior cancer diagnosis has a heterogeneous effect on the survival of patients with lung cancer aged <65 years across different stages, but further prospective studies are still warranted.

Adherence to National Guidelines and Effect on Overall Survival in Younger Patients with Colon Cancer: A National Cancer Database Study

Feldman, Hope MD; Callahan, Morgan DO; Young, Katelyn A. BS; Fluck, Marcus BS; Shabahang, Mohsen MD, PhD, FACS; Buzas, Christopher J. DO, FACS; Long, Kevin C. MD; Blansfield, Joseph A. MD, FACS Author Information

P026 Impact of Prior Cancer History on the Overall Survival of Younger Patients with Lung Cancer

P026 Impact of Prior Cancer History on the Overall Survival of Younger Patients with Lung Cancer