Completion Of Primary Therapy Research Articles

Impact of workplace accommodations on long-term work outcomes in a diverse sample of breast cancer survivors.

501 Background: Low-income and racial/ethnic minority workers in the US have limited access to work accommodations, such as schedule flexibility, if they become ill. Access to such accommodations is a key predictor of work status immediately after treatment for breast cancer. We evaluated the impact of accommodations on long-term work outcomes in a demographically diverse cohort of breast cancer survivors. Methods: We surveyed pre-diagnosis employed women, aged 18-64, who spoke Chinese, English, Korean, or Spanish and were undergoing treatment for stage I-III breast cancer in New York City. Recruitment was enriched for racial/ethnic minority and immigrant status. Surveys were administered (telephone or online) during treatment (baseline) and 4 months after completion of primary therapy. Long-term work status was evaluated in brief surveys 1 and 2 years later. The primary outcome was post-treatment work status (working full- or part-time vs. any other work status). We used X2 and Fisher's Exact Tests to examine associations between participant characteristics and work status, and logistic regression to adjust for relevant characteristics in multivariable analyses. Results: From 06/2012 to 08/2018, 497 participants completed baseline surveys; 479 completed 4-month post-treatment surveys, and 401 and 387 reported on their work status 1 and 2 years later. Overall, 22% self-identified as Black, 22% Chinese, 7.1% Korean, 27% Latina, 19% non-Latina white, and 2.7% as other; 58% were born outside of the US. Post-treatment work status remained relatively stable over time: 29% were not working 4 months after treatment completion, and 26% and 25% were not working 1 and 2 years later. Non-Latina white women were most likely to be working after treatment completion (89%), followed by Korean (74%), Black (73%), Chinese (69%), and Latina women (61%; overall p<0.001). Similar trends were observed 1 and 2 years later. Participants who reported that their employer had been accommodating in their 4-month post-treatment survey were more likely to be working 4 months after completion of treatment (83% vs. 57% of those with unaccommodating employers, p<0.001) and 1 year (85% vs. 60%, p<0.001) and 2 years later (84% vs. 65%, p<0.001). The relationship between employer accommodations and post-treatment work status across all time points remained significant after controlling for age, race/ethnicity, language, household income as a % of the Federal Poverty Level, job type, and receipt of chemotherapy. Conclusions: In this diverse cohort of breast cancer survivors, relative to work status 4 months post-treatment, work status was relatively stable 1 and 2 years later. Women whose employers had been accommodating during treatment were more likely to be working 1 and 2 years later. Increasing access to accommodations could improve long-term work outcomes and abrogate disparities in patients who undergo cancer therapy.

Abstract OT2-06-01: Breast Cancer Cohort of the Comprehensive Outcomes for After Cancer Health (COACH) Study: Study Protocol

Abstract Background: Women with breast cancer account for the largest cohort (23%) of over 18 million cancer survivors in the United States. Of the nearly 4 million breast cancer survivors, many, including individuals with metastatic breast cancer, will require lifelong treatment for chronic conditions. As part of a multi-site study including diverse tumor types, breast cancer survivors are being recruited to explore the feasibility and outcomes of a digital health coaching (DHC) program following the completion of primary therapy to support self-management of symptoms and general wellness. Trial design: A randomized-wait list control design will evaluate outcomes related to engagement in a DHC program following completion of primary therapy. Participants will be enrolled in a 6-month DHC program delivering evidence-based content via weekly calls, text, and email, in addition to usual support from their respective healthcare teams. The intervention group will receive coaching upon enrollment. The control group will receive coaching after a 6-month monitoring period. Twelve months of longitudinal clinical, patient-reported outcomes, activity tracking (via Fitbit), and microbiome data will be collected from both groups. Eligibility criteria: The breast cancer cohort will consist of individuals with both localized and metastatic disease within 1 year of completion of primary therapy, defined as treatment of curative intent, first-line or later, from which the individual is advancing to active surveillance or follow-up, with or without maintenance therapy. All study participants must be >18 years old, able to read and speak English, have access to mobile technology, and agree to wear and have data collected from an activity tracker. Specific aims: 1) Assess the feasibility and acceptability of a DHC program and its effect on participant health self-efficacy; 2) characterize associations between participant symptoms, physical/psychosocial well-being, and health self-management and gut microbiota changes; and 3) explore patient-generated health data outcomes among participants (patient reported and wearable biometrics outcomes). Statistical methods: Feasibility and acceptability will be assessed through descriptive statistics. Feasibility for this study is defined as a retention rate ≥70%, and acceptability is defined as ≤20% scoring “not at all helpful.” Secondary aims will be assessed using linear mixed models. Cross-cohort analysis of physical function, measured by the PROMIS Physical Function 10a, will be conducted. Assuming a power of 0.8 and significance level of .05, we will be able to detect a 2.51 difference in PROMIS score means between the control and intervention group (SD 10) with a sample of 500 total participants. Sub-group analysis will be conducted with the anticipated 250 participants in the breast cancer cohort with a focus on feasibility, acceptability, and descriptive and exploratory endpoints for this population as a whole and comparing early stage and metastatic participants. Target and present accruals: 500 individuals with diverse tumor types will be enrolled across 5 collaborating sites, of which 4 ill include individuals with breast cancer. An estimated 250 breast cancer participants (approximately 50% of the total study population), including 150 with de novo or progressive metastatic breast cancer, are planned to be recruited. To date, 1 Midwestern site has enrolled the first 7 breast cancer survivors. Two additional sites plan to enroll in July 2022, with the remaining 2 sites to begin enrollment by the end of 2022. Citation Format: Robin M. Lally, Rachael L. Schmidt, Gisele Tlusty, Elizabeth K. Arthur, Laura K. Flora, Jessica L. Krok-Schoen, Jessica T. Jones, Meagan Whisenant, Abbey Kaler, Debu Tripathy, Leorey Saligan, Marilyn Hammer, Austin Barr, Lindsey Jackson, Jennifer Loftis, Kelly J. Brassil. Breast Cancer Cohort of the Comprehensive Outcomes for After Cancer Health (COACH) Study: Study Protocol [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 OT2-06-01.

Predictive value of highly sensitive basal versus stimulated thyroglobulin measurement in long-term follow-up of thyroid cancer.

Recurrence of differentiated thyroid cancer (DTC) is associated with reduced quality of life, and therefore, early identification of patients at risk is urgently needed.Here we investigated the predictive power of various cut-off values of single stimulated thyroglobulin (s-Tg) and single highly sensitive measured, unstimulated thyroglobulin (u-hsTg) measurements close to the end of primary therapy for recurrence-free survival (RFS) in long-term follow-up (>10 years) of patients with DTC. In DTC patients with adjuvant radioiodine therapy, we assessed retrospectively u-hsTg (6 ± 3 months before s-Tg measurement) and s-Tg measurements (≤24 months after last radioiodine therapy). Positive predictive (PPV)/negative predictive values (NPV) of various cut-off values (s-Tg: 0.5/1.0 ng/mL; u-hsTg: 0.09/0.2 ng/mL) for patient outcomes as well as additional factors associated with disease development were analyzed. In total, 175 patients were retrospectively reviewed (tumor recurrence: n = 14/complete remission: n = 161). Examined cut-off values for s-Tg and u-hsTg showed significant predictive power for RFS (log-rank: all P < 0.001). NPV/PPV for s-Tg were 98.6%/36.4%, respectively (0.5 ng/mL cut-off) and 96.7%/42.9%, respectively (1.0 ng/mL cut-off); those for u-hsTg were 97.3%/35.7%, respectively (0.09 ng/mL cut-off) and 95.2%/85.7%, respectively (0.2 ng/mL cut-off). U-hsTg (P < 0.001) and patient age (P < 0.05) were significantly associated with tumor recurrence. One-third of patients with tumor recurrence in the course initially showed undetectable u-hsTg after completion of primary therapy. With >10 years of follow-up, both s-Tg and u-hsTg have a comparably high predictive power for RFS, while only u-hsTg was significantly associated with a recurrence event.Serial u-hsTg measurements seem warranted since patients with tumor recurrence during follow-up may have an undetectable tumor marker at baseline.

Mind-body medicine in integrative uro-oncology : Studies and areas of application

Mind-body medicine (MBM) complements somatically oriented medical practice with behavioral and lifestyle-oriented approaches: Thus, health-promoting attitudes and behaviors are strengthened in everyday life. In integrative oncology, it helps promote emotional and physical well-being. Guideline recommendations and the current study situation in integrative uro-oncology are presented. During and after completion of primary therapy, mindfulness-based stress reduction (MBSR) shows positive effects on anxiety, stress, and fatigue. However, it appears that the offer needs to be better tailored to the needs of prostate cancer patients. The effects of yoga are well documented, especially on fatigue, quality of life, and sexual function. Prostate cancer patients also showed asignificantly increased immune response after completing ayoga intervention. Tai Ji Quan/Qigong improve quality of life, fatigue, and other symptoms. Hypnosis-especially in the palliative setting-mitigates anxiety, and relaxation techniques alleviate sleep problems and nausea/vomiting. Multimodal services improve quality of life on numerous levels. Higher resilience correlates with better quality of life and stronger male self-esteem. MBSR alleviates many symptoms but needs to be adapted to the needs of prostate cancer patients; yoga and Tai Ji Chuan/Qigong alleviate fatigue and improve quality of life. Hypnosis and relaxation training reduce nausea/vomiting, and improve sleep and anxiety. Resilience promotion is important to support oncological patients.

Improvement of functional outcome for patients with newly diagnosed grade 2 or 3 gliomas with co-deletion of 1p/19q – IMPROVE CODEL: the NOA-18 trial

BackgroundGiven the young age of patients with CNS WHO grade 2 and 3 oligodendrogliomas and the relevant risk of neurocognitive, functional, and quality-of-life impairment with the current aggressive standard of care treatment, chemoradiation with PCV, of the tumour located in the brain optimizing care is the major challenge.MethodsNOA-18 aims at improving qualified overall survival (qOS) for adult patients with CNS WHO grade 2 and 3 oligodendrogliomas by randomizing between standard chemoradiation with up to six six-weekly cycles with PCV and six six-weekly cycles with lomustine and temozolomide (CETEG) (n = 182 patients per group accrued over 4 years) thereby delaying radiotherapy and adding the chemoradiotherapy concept at progression after initial radiation-free chemotherapy, allowing for effective salvage treatment and delaying potentially deleterious side effects. QOS represents a new concept and is defined as OS without functional and/or cognitive and/or quality of life deterioration regardless of whether tumour progression or toxicity is the main cause. The primary objective is to show superiority of an initial CETEG treatment followed by partial brain radiotherapy (RT) plus PCV (RT-PCV) at progression over partial brain radiotherapy (RT) followed by procarbazine, lomustine, and vincristine (PCV) chemotherapy (RT-PCV) and best investigators choice (BIC) at progression for sustained qOS. An event concerning a sustained qOS is then defined as a functional and/or cognitive and/or quality of life deterioration after completion of primary therapy on two consecutive study visits with an interval of 3 months, tolerating a deviation of at most 1 month. Assessments are done with a 3-monthly MRI, assessment of the NANO scale, HRQoL, and KPS, and annual cognitive testing. Secondary objectives are evaluation and comparison of the two groups regarding secondary endpoints (short-term qOS, PFS, OS, complete and partial response rate). The trial is planned to be conducted at a minimum of 18 NOA study sites in Germany.DiscussionqOS represents a new concept. The present NOA trial aims at showing the superiority of CETEG plus RT-PCV over RT-PCV plus BIC as determined at the level of OS without sustained functional deterioration for all patients with oligodendroglioma diagnosed according to the most recent WHO classification.Trial registrationClinicaltrials.govNCT05331521. EudraCT 2018–005027-16.

Defining the Spectrum, Treatment and Outcome of Patients With Genetically Confirmed Gorlin Syndrome From the HIT-MED Cohort.

Gorlin syndrome is a genetic condition associated with the occurrence of SHH activated medulloblastoma, basal cell carcinoma, macrocephaly and other congenital anomalies. It is caused by heterozygous pathogenic variants in PTCH1 or SUFU. In this study we included 16 patients from the HIT2000, HIT2000interim, I-HIT-MED, observation registry and older registries such as HIT-SKK87, HIT-SKK92 (1987 – 2020) with genetically confirmed Gorlin syndrome, harboring 10 PTCH1 and 6 SUFU mutations. Nine patients presented with desmoplastic medulloblastomas (DMB), 6 with medulloblastomas with extensive nodularity (MBEN) and one patient with classic medulloblastoma (CMB); all tumors affected the cerebellum, vermis or the fourth ventricle. SHH activation was present in all investigated tumors (14/16); DNA methylation analysis (when available) classified 3 tumors as iSHH-I and 4 tumors as iSHH-II. Age at diagnosis ranged from 0.65 to 3.41 years. All but one patient received chemotherapy according to the HIT-SKK protocol. Ten patients were in complete remission after completion of primary therapy; four subsequently presented with PD. No patient received radiotherapy during initial treatment. Five patients acquired additional neoplasms, namely basal cell carcinomas, odontogenic tumors, ovarian fibromas and meningioma. Developmental delay was documented in 5/16 patients. Overall survival (OS) and progression-free survival (PFS) between patients with PTCH1 or SUFU mutations did not differ statistically (10y-OS 90% vs. 100%, p=0.414; 5y-PFS 88.9% ± 10.5% vs. 41.7% ± 22.2%, p=0.139). Comparing the Gorlin patients to all young, SHH activated MBs in the registries (10y-OS 93.3% ± 6.4% vs. 92.5% ± 3.3%, p=0.738; 10y-PFS 64.9%+-16.7% vs. 83.8%+-4.5%, p=0.228) as well as comparing Gorlin M0 SKK-treated patients to all young, SHH activated, M0, SKK-treated MBs in the HIT-MED database did not reveal significantly different clinical outcomes (10y-OS 88.9% ± 10.5% vs. 88% ± 4%, p=0.812; 5y-PFS 87.5% ± 11.7% vs. 77.7% ± 5.1%, p=0.746). Gorlin syndrome should be considered in young children with SHH activated medulloblastoma, especially DMB and MBEN but cannot be ruled out for CMB. Survival did not differ to patients with SHH-activated medulloblastoma with unknown germline status or between PTCH1 and SUFU mutated patients. Additional neoplasms, especially basal cell carcinomas, need to be expected and screened for. Genetic counselling should be provided for families with young medulloblastoma patients with SHH activation.

Conservative management of rhabdomyosarcoma of uterine cervix: A case series

Background: Rhabdomyosarcoma (RMS) of the uterine cervix is a rare disease, usually affects pediatric and adolescent girls. Excellent treatment outcomes have been reported with combined modality treatment employing surgery, chemotherapy, and radiation therapy. Fertility-sparing treatment options can be considered in young patients without compromising outcome. Aim: This study aimed to analyze the outcome of patients with cervical RMS who were managed conservatively. Materials and Methods: We retrospectively reviewed the clinical and pathologic data of all patients with cervical RMS who were registered at our institution during 1995–2010. Long-term outcome data of patients who had conservative surgery were analyzed. Results: During this period, six patients with cervical RMS were registered. Five patients, managed conservatively, were eligible for analysis. The median age was 20 years (range: 14–21 years). Excessive vaginal discharge was the most common presenting symptom (n = 3). All patients initially had either a polypectomy (n = 4) or gross tumor resection (n = 1) followed by received chemotherapy with VAC regimen (Vincristine, Actinomycin-D and Cyclophosphamide). One patient received local radiation (HDR brachytherapy) for microscopic residual disease. All patients were disease-free at the completion of primary therapy. At a median follow-up of 10 years, four patients remain relapse-free; three, having retained fertility, had successful pregnancies and healthy children. One patient developed ovarian failure consequent to radiation treatment but remains disease free. One patient developed local recurrence, 8 years after primary treatment, and underwent salvage hysterectomy followed by second-line chemotherapy. This patient too remains disease-free, 3 years after salvage treatment. Conclusion: RMS of the uterine cervix is highly curable in early stages. The focus now is on improving the quality of life by reducing treatment-related morbidity and late effects. Fertility preservation approaches should be considered in young females with RMS of cervix.

Current Status of Circulating Tumor Cells, Circulating Tumor DNA, and Exosomes in Breast Cancer Liquid Biopsies.

Breast cancer is the most common cancer among women worldwide. Although the five-, ten- and fifteen-year survival rates are good for breast cancer patients diagnosed with early-stage disease, some cancers recur many years after completion of primary therapy. Tumor heterogeneity and clonal evolution may lead to distant metastasis and therapy resistance, which are the main causes of breast cancer-associated deaths. In the clinic today, imaging techniques like mammography and tissue biopsies are used to diagnose breast cancer. Even though these methods are important in primary diagnosis, they have limitations when it comes to longitudinal monitoring of residual disease after treatment, disease progression, therapy responses, and disease recurrence. Over the last few years, there has been an increasing interest in the diagnostic, prognostic, and predictive potential of circulating cancer-derived material acquired through liquid biopsies in breast cancer. Thanks to the development of sensitive devices and platforms, a variety of tumor-derived material, including circulating cancer cells (CTCs), circulating DNA (ctDNA), and biomolecules encapsulated in extracellular vesicles, can now be extracted and analyzed from body fluids. Here we will review the most recent studies on breast cancer, demonstrating the clinical potential and utility of CTCs and ctDNA. We will also review literature illustrating the potential of circulating exosomal RNA and proteins as future biomarkers in breast cancer. Finally, we will discuss some of the advantages and limitations of liquid biopsies and the future perspectives of this field in breast cancer management.

Single or two drug combination therapy as initial treatment for low risk, gestational trophoblastic neoplasia. A Canadian analysis

IntroductionLow risk gestational trophoblastic neoplasia, WHO prognostic score of 0 to 6, is highly curable. There is no consensus on the optimal chemotherapy. Common regimens are q2wk actinomycin-D (ACT-D), weekly intramuscular methotrexate (MTX) or multi-day MTX. Combination MTX/ACT-D is rarely used. MethodsA four centre, retrospective cohort study was carried out comparing commonly used regimens: weekly MTX, q2weekly ACT-D and q2 weekly MTX and ACT-D. Results412 patients - 196 MTX/ACT-D, 107 MTX, 109 ACT-D - were treated between October 1994 and January 2019. Initial regimen failure (secondary to resistance or toxicity) occurred in 37% (MTX), 21% (ACT-D) and 5% (MTX/ACT-D). Relapse after completion of primary therapy (initial plus switch to another therapy if needed) was rare (0–5%). All eventually were cured. Mean number of cycles required to achieve remission were 10.1 (MTX), 7 (ACT-D) and 5.6 (MTX/ACT-D) with corresponding mean treatment durations of 3.12, 2.9 and 2.26 months. Dosage reductions occurred in 3% (MTX), 0% (ACT-D) and 29% (MTX/ACT-D). Higher failure rates occurred with WHO prognostic scores of 5 to 6 and HCG levels ≥10,000. SummaryInitial regimen failure ie the need to switch to an alternative treatment was more common with MTX. ACT-D and MTX/ACT-D were similar within prognostic score 0–4 or HCG < 10,000. ACT-D then appears the better initial choice with its superior convenience. Above these levels primary failure rates are less with MTX/ACT-D, making it a better choice.

Long-Term Outcome of Relapsed Acute T-Lymphoblastic Leukemia (T-ALL) in Children and Adolescents

Introduction Despite improvements in first-line treatment of childhood T-ALL, relapse remains the main cause of treatment failure. Patients with T-ALL experiencing leukemia recurrence have a dismal outcome, mostly due to a failure to achieve a second complete remission (CR) or to subsequent relapse. Assessment of minimal residual disease (MRD) may allow identifying subsets of patients with different prognosis. We analyzed the outcomes of 141 Italian children and adolescents who experienced T-ALL relapse after frontline multicenter AIEOP-BFM ALL treatment trials. Methods: This retrospective study aimed at describing the outcomes of Italian patients with T-ALL who were enrolled in the AIEOP-BFM ALL2000, 2006 and 2009 trials and subsequently experienced disease relapse. Among the 750 T-ALL Italian patients enrolled in the above-mentioned trials, 141 had a disease recurrence (70/251 patients in ALL2000 trial, 29/190 in ALL2006 trial, and 42/309 in ALL2009 trial). Molecular MRD monitoring after induction therapy for leukemia relapse was available for 38 patients. Results: The 141 patients, 113 males and 28 females, had a median age of 9 years at diagnosis (range 1-17) and 10 at relapse (range 2-19). At diagnosis, 7 patients were allocated to the Standard (SR), 45 to the Medium (MR), and 89 to the High Risk (HR) group, respectively. Thirty-four (4 MR and 30 HR patients) of these children were given allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 1st CR and 41 had received central nervous system (CNS) radiotherapy. Relapses were classified as very early (occurring &lt;18 months from diagnosis), early (occurring ≥18 months from diagnosis and &lt;6 months after completion of primary therapy), and late (occurring &gt;6 months after the end of the frontline protocol) in 92, 36, and 13 patients, respectively. Site of relapse was isolated bone marrow (BM) in 74 patients, combined BM/extramedullary (EM) in 23 patients, and isolated EM in 44 patients (involving a single EM site in 37 cases and &gt;1 EM site in 7 cases; CNS was involved in 29 patients). At the time of relapse, 7 patients were treated according to AIEOP ALL REC98 Trial, 57 according to AIEOP ALL REC2003 Trial, while the remaining 77 patients received other combination of chemotherapy. After reinduction/consolidation treatment, 58 patients were given allo-HSCT from either a matched family donor (16) or an unrelated donor (UD, 31 patients, of which 21 from a matched UD and 10 from a mismatched UD) or an HLA-partially matched relative (11). With a median follow-up of 7.5 years (range 2-14), 34 patients are currently alive; 17 of these patients had EM isolated relapse, which was very early in 13 cases, and 17 had BM involvement at relapse, with late relapse in 8 cases. The 8-year overall survival (OS) of the whole cohort was 23.3% (95% CI 16.5-30.7) (Figure 1A). Isolate EM relapse (Figure 1B) and late relapses were associated with a better OS probability. Both factors remained statistically significant in multivariable analysis. Moreover, in univariable analysis a better prognosis was observed in patients treated more recently (i.e., after year 2008) (8-year OS 31.8% vs 16.2%, p=0.01). After allo-HSCT, 29 patients are currently alive, while the remaining 29 patients died from progressive disease (21) or transplant-related causes (8), leading to a 8-year OS for patients given allo-HSCT in 2nd RC of 48.5% (95% CI 34.7-61.0). Of the 83 children given sole chemotherapy, 5 are currently alive, while the remaining 78 died due to progressive disease (53), organ-failure (7), infection (9), or other causes (9). MRD monitoring was performed for 38/97 patients with BM involvement (5 with late, 13 with early, and 20 with very early relapse, respectively). Patients with a post-induction MRD &lt;10-3 showed a reduced incidence of relapse (Figure 1C), resulting into better probability of 8-year OS (Figure 1D) in comparison to patients with higher MRD levels. Conclusions: Our results confirm that T-ALL relapse, especially if involving BM and occurring within 6 months from treatment discontinuation is still associated with poor prognosis, although in the last 10 years a higher proportion of children with relapsed T-ALL has been rescued by second line therapy, including transplantation. In this Italian retrospective cohort, a MRD value &gt;10-3 at the end of induction therapy predicts a miserable outcome, this finding allowing to identify patients eligible to experimental therapies. Figure 1 Disclosures Merli: Novartis: Honoraria; Amgen: Honoraria; Bellicum: Consultancy; Sobi: Consultancy. Rizzari:JazzPharma, Shire, medac , Sigma-Tau, Baxalta, Shire and Servier: Consultancy, Honoraria; Together with study group from Shire, medac , Sigma-Tau, Baxalta, Shire and Servier: Research Funding. Parasole:Servier: Honoraria; Baxalta: Honoraria; Eusapharma: Honoraria. Locatelli:bluebird bio: Consultancy; Miltenyi: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Systemic HD-MTX for CNS prophylaxis in high-risk DLBCL patients: a prospectively collected, single-center cohort analysis.

We evaluated the efficacy of systemic high-dose methotrexate (HD-MTX) for CNS prophylaxis in a prospectively recruited cohort of DLBCL patients at high risk of CNS relapse. High-risk CNS relapse was defined as the involvement of ≥ 2 extranodal sites with elevated lactate dehydrogenase (LDH); CNS international prognostic index (CNS-IPI) ≥ 4; or involvement of high-risk extranodal sites, including bone marrow, breasts, testes, and paranasal sinuses. Overall, 130 patients who received at least two cycles of standard chemoimmunotherapy were evaluated; of these, 64 patients received additional systemic HD-MTX, either on day 15 of alternating cycles or 2-5weeks after completion of primary therapy. Patients receiving HD-MTX showed a generally higher risk of CNS relapse than the other 66 patients not receiving prophylaxis. The estimated 2-year cumulative CNS relapse, progression-free survival and overall survival rates were 8.1%, 66.3%, and 77.5%, respectively, in patients who received systemic HD-MTX and 6.9%, 67.4%, and 71.4%, respectively, in patients without prophylaxis, with no significant between-group differences. Although this study does not show that systemic HD-MTX is definitively effective, these results may be of help to other researchers investigating the utility of HD-MTX prophylaxis in mitigating negative risk factors.

Association of Oral Human Papillomavirus DNA Persistence With Cancer Progression After Primary Treatment for Oral Cavity and Oropharyngeal Squamous Cell Carcinoma

Detection of persistent oral human papillomavirus (HPV) DNA may be associated with recurrence of HPV-positive head and neck squamous cell carcinoma (HNSCC). To evaluate the dynamics of oral HPV DNA detection and associations with disease outcomes in patients with HPV-positive and HPV-negative HNSCC. This prospective, 2-institution, tertiary referral center study of 396 patients with newly diagnosed oral cavity or oropharyngeal HNSCC was performed from July 11, 2011, to May 7, 2016. Oral rinse samples were prospectively collected at diagnosis and at completion of primary therapy. Weekly oral rinse samples were collected during radiotherapy. Purified tumor and oral rinse sample DNA were evaluated for 37 HPV types, and viral load was quantified by type-specific real-time polymerase chain reaction. Cancers were stratified by tumor HPV status, and HPV was classified as tumor type if identical to that detected in the tumor or nontumor type. Prevalence of HPV DNA before, during, and after therapy. Associations between tumor-type and nontumor-type oral HPV DNA detection and recurrence-free and overall survival were evaluated. Of the 396 patients (median age, 59 years [range, 19-96 years]; 295 [74.5%] men; and 354 [89.4%] white race/ethnicity), 217 had oropharyngeal cancer; 170, oral cavity cancer; and 9, unknown primary HNSCC. The prevalence of oral HPV detection at diagnosis was higher among patients with HPV-positive compared with HPV-negative HNSCC (24 of 194 [84.2%] vs 170 of 202 [12.4%]; P < .001). Oral HPV-16 DNA had an 81% sensitivity and 100% specificity for HPV-16-positive HNSCC. The prevalence and load of tumor-type HPV decreased significantly during primary therapy with odds ratio for probability of infection with each increasing month after diagnosis (0.41; 95% CI, 0.33-0.52; P < .001), whereas those of nontumor types did not (1.01; 95% CI, 0.97-1.06; P = .62). Current smoking was significantly associated with a reduced clearance of tumor-type HPV DNA (hazard ratio [HR], 0.54; 95% CI, 0.32-0.93). Two-year overall survival was significantly lower among the HPV-positive patients with persistent detection of tumor-type HPV after therapy than among those without detectable tumor-type DNA after therapy (68% vs 95%; adjusted HR, 6.61; 95% CI, 1.86-23.44; P = .003), as was recurrence-free survival (55% vs 88%; adjusted HR, 3.72; 95% CI, 1.71-8.09; P < .001). No associations were observed for nontumor type HPV DNA among patients with HPV-positive or HPV-negative HNSCC. Prevalence and viral load of tumor-type HPV DNA decreased rapidly with therapy, and persistent detection was associated with increased risk of recurrence and death. Analysis of tumor type HPV DNA has considerable promise as a biomarker for treatment response and risk of progression.

Randomized phase II trial of patient-specific dendritic cell vaccines loaded with autologous tumor antigens versus autologous monocytes in patients with primary advanced ovarian cancer.

TPS10 Background: With standard debulking surgery and combination chemotherapy (adjuvant ± neoadjuvant) the 5-year survival for women with newly diagnosed advanced epithelial ovarian cancer (stage III or IV) is less than 40%. After completion of primary therapy there is an opportunity to introduce an immunotherapy modality in an effort to improve long-term survival. In patients with metastatic melanoma, patient-specific vaccines consisting of autologous dendritic cells (DC) loaded with autologous tumor antigens (ATA) derived from a short-term autologous tumor cell line were associated with minimal toxicity and a 5-year survival of 50% in a single arm trial, and more than doubled median survival (43 vs. 20 months) in a randomized trial. Newly diagnosed patients with ovarian cancer might benefit from addition of such patient-specific therapeutic vaccines (DC-ATA) to standard therapy. Methods: This is a double-blind, 2:1 randomized trial comparing adjunctive treatment with DC-ATA to autologous monocytes (MC) in patients with newly diagnosed stage III or IV epithelial cancer of the ovary, fallopian tube, or peritoneum. Patients eligible for randomization are those who have completed or discontinued standard primary therapy, have a Karnofsky performance status ≥70, have an autologous tumor cell line, and have a monocyte product from which DC can be derived. The tumor cell line is derived from fresh tumor; MC are derived from leukapheresis, and MC are converted to DC by incubation with GM-CSF and IL-4. Patients are stratified by whether there is no evidence of disease at completion of primary therapy, and then are randomized, typically 6 to 7 months after tumor collection. Treatment can begin about 4 weeks from randomization. The trial has been open at a single site since mid-November 2017; the first tumor was collected in December. Appropriate tumor samples have been submitted from 11 patients and all 11 have resulted in cell lines. The first patient was randomized in May 2018. As of October 2018 four patients had been randomized and all four had started treatment. Additional clinical sites are being initiated. Clinical trial information: NCT02033616.

CA125 Value As an Indicator for Imaging for Detection of CA Ovary Recurrence After Primary Treatment

Background: GCIG states that CA125 value double of upper limit of normal during follow-up after primary treatment is a criteria for further intervention. However, in our institution we found that significant number of women with a CA 125 &gt; 35 u/mL have recurrent disease on imaging. Aim: To compare values of CA125 rise as an indicator for imaging for detection of recurrence after primary treatment. Methods: It was retrospective observational study. 64 women with stage III and IV epithelial ovarian cancer who had normal CA125 on completion of primary therapy from January 2012 to December 2016 at Tata Medical Center, Kolkata, India were included in the study. These women were followed up with Ca125 three monthly for 2 years then six monthly. CA 125 doubling from posttreatment baseline or exceeding 35 u/mL were investigated with CT imaging. Data were collected from hospital management system electronic medical records. Results: Out of 146 patients who underwent IDS 64 (43.8%) had normal CA125 post treatment. 2 patients with doubling of Ca125 but &lt; 35 u/mL had recurrence, all of whom had R0 during IDS. 1 patient with normal CA 125 had clinical recurrence and this patient had R2 disease during IDS. 2 patients with normal CA 125 had recurrence on radiology only and they had R0 during IDS. 18 (24%) had radiologic recurrence when CA125 was &gt; 35 u/mL out of which14 patients had R0 and 4 patients R1 disease during IDS. 41 patients had recurrence detected on radiology when CA125 was &gt; 70 u/mL. Out of these 27 had R0, 11 patients had R1 and 3 patients had R2 disease on IDS. 78% of R0 patients had disease recurrence when CA125 was &gt; 35 u/mL. Conclusion: Imaging should be considered when CA125 rises &gt; 35u/mL, rather than waiting for it to double the upper limit of normal, so that early detection of recurrence can initiate timely treatment. Rise of CA125 above 35 u/mL is a good criteria for imaging to detect recurrence even in women with R0 resection. CA125 can be used as a good tool for follow-up especially in low resource setting where people cannot afford routine imaging.

Survivorship issues as determinants of quality of life after breast cancer treatment: Report from a limited resource setting

ObjectivesQuality of life (QOL) in breast cancer survivors is affected by various long term sequelae of breast cancer treatment. The present study was conducted with the objectives to estimate prevalence of various survivorship issues, and to identify those which are most predictive of limitations in QOL after completion of primary therapy. Material &MethodsThis study was conducted in 230 breast cancer survivors (BCs) and 112 controls at an academic centre in Northern India. Assessment of QOL was done by SF-36 and FACT-B questionnaires. Survivorship issues were noted from a checklist of 14 commonly reported symptoms. Main outcome measures were (1) frequencies of survivorship issues and QOL scores among three groups of survivors divided on the basis of time elapsed since treatment (<2, 2–5, and >5 year follow up) (2) Issues most predictive of limitations in QOL, identified by stepwise logistic regression analysis. ResultsLonger term BCs showed higher QOL scores as compared to those in early follow up. However their QOL scores remained poorer compared to healthy women. The most prevalent survivorship issues were fatigue (60%), restriction of shoulder movement (59.6%), body and joint pain (63.5%), chemotherapy induced cessation of menstruation (73.3%) and loss of sexual desire (60%). Issues which had maximum impact on QOL scores were emotional distress (r = −11.375), fatigue (r = −9.27) and premature menopause (r = −2.085) and its related symptoms. ConclusionManagement of these issues should be priority areas for supportive care, especially in settings with limited resource.

Diet Quality, Inflammation, and Quality of Life in Breast Cancer Survivors: A Cross-Sectional Analysis of Pilot Study Data

BackgroundModifiable lifestyle factors, such as diet quality, could reduce inflammation and improve quality of life (QOL) in breast cancer survivors, but data are inconclusive. ObjectiveTo determine whether diet quality, as measured by Healthy Eating Index-2010 (HEI-2010) score, is associated with inflammation, health status, or functional outcomes affecting QOL in survivors of early-stage breast cancer. DesignThis is a cross-sectional, secondary analysis of baseline data collected from breast cancer survivors after completion of primary therapy and before random assignment to a pilot nutritional intervention aimed at reducing side effects of aromatase inhibitor treatment. Participants/settingParticipants were 44 postmenopausal women with stage I to III endocrine receptor–positive breast cancer receiving outpatient care at a midwestern cancer center between November 2011 and October 2013. Main outcome measuresPrimary outcomes were serum proinflammatory cytokines (interleukin-6 [IL-6], IL-17, and tumor necrosis factor-α receptor 2 [TNFR-2]). Secondary outcomes included QOL measured by the Stanford Health and Disability Questionnaire and the Functional Assessment of Cancer Therapy–Breast with Endocrine Subscale. Statistical analyses performedPearson correlation coefficients (r) and linear regression models were used to evaluate the relationship of dietary variables with inflammatory cytokines and QOL measures. ResultsA higher overall HEI-2010 score (healthier diet) was associated with lower IL-6 (r=−0.46; P=0.002) and TNFR-2 (r=−0.41; P=0.006); however, associations were attenuated by body mass index (BMI) (IL=6 [r=−0.26; P=0.10]; TNFR-2 [r=−0.30; P=0.06]). In women with prior chemotherapy, a higher HEI-2010 score was strongly associated with lower IL-6 (r=−0.67; P=0.009) and TNFR-2 (r=−0.59; P=0.03) after BMI adjustment. There were no significant correlations between HEI-2010 score and QOL measures after adjustment for BMI. ConclusionsThese data suggest the need for more rigorous investigation into the relationship of diet quality, BMI, and inflammation in breast cancer survivors.

Survivorship care plans: Recommended vs delivered care.

10076 Background: The Committee on Cancer set a benchmark for the provision of survivorship care plans (SCP) to ≥50% of early cancer patients by the end of 2017 despite limited data indicating benefit. One hypothesis is that SCP will reduce overuse of medical care in survivors. Methods: We performed a retrospective review of all patients with early breast cancer (BC) who were seen by a single nurse practitioner (NP) for provision of SCP after completion of primary therapy (surgery, radiation +/- chemotherapy). We evaluated adherence to recommendations for follow-up (FU) care and testing in accordance with established guidelines. Results: Between August 2013 and December 2014, 152 patients received SCP after completion of primary therapy (median 2 months, range 0-27). 98% of SCP were given to patients, but only 38% were sent to primary care providers (PCP). Median FU was 23 months. Among 130 patients who did not undergo bilateral mastectomy for whom surveillance breast imaging (SBI) was recommended, 10 (8%) had 1st SBI ≥3 months earlier than time recommended (TR), 102 (78%) within 2 months of TR, 12 (9%) ≥3 months after TR, and 6 (5%) lacked confirmation of 1st SBI. Among 113 in whom 2nd SBI dates were specified, 25 (23%) had SBI ≥3 months earlier than TR, 62 (55%) within 2 months of TR, 7 (6%) ≥3 months after TR, and 18 (16%) lacked confirmation of 2nd SBI. Among 71 patients for whom first medical oncology (MO) FU visit dates are known, 64 (90%) occurred within 3 months of TR and among 81 patients for whom first radiation oncology (RO) FU visit dates are known, 67 (83%) occurred within 3 months of TR. However, among 47 patients for whom first FU visit dates with at least 2 types of providers (MO, RO and/or surgery) are known, 15 (32%) visited 2 providers within 2 months of one other. During the 1styear after completion of primary therapy, 22% underwent body imaging (CT, PET-CT, or bone scan) and 21% had liver function tests. Conclusions: Despite provision of a SCP to patients, PCP were often not notified and healthcare utilization exceeded recommendations. Nearly a third of patients had redundant visits, a fourth had SBI earlier than recommended, and a fifth had body imaging and lab testing. Ongoing efforts are needed to coordinate care and minimize unnecessary testing in BC survivors.

The Impact of Lifestyle Interventions in Breast Cancer Women after Completion of Primary Therapy: A Randomized Study.

Many breast cancer survivors have unmet physical and psychological needs. Therefore, current study aimed to evaluate the impact of a lifestyle interventions program on fatigue, quality of sleep, quality of life (QoL), and body mass index (BMI) in women with breast cancer. This randomized controlled trial study (RCT) was carried between 2012 and 2015, and included 80 women with breast cancer. They were divided into two groups via a random allocation process: 40 women were allocated to the lifestyle interventions group, and 40 to the control group. Women in the lifestyle group received dietary energy-restriction training and practiced supervised aerobic exercises for 45-60 minutes three times per week throughout 24 weeks and the control group continued their routine life. Differences between the two groups were significantly high for those who participated in the intervention group; this group reported significantly less fatigue, less BMI, improved QoL and better quality of sleep as compared to the control group (p<0.05). Breast cancer survivors may physically and psychologically benefit from participating in a healthy lifestyle interventions program. This program can help relieve fatigue, maintain healthy BMI, improve QoL and enhance the quality of sleep in women with breast cancer. Lifestyle interventions program may provide a non-pharmacologic adjunctive therapy for symptom management in breast cancer survivors.

Functional Imaging in Children and Adolescents with Relapsed or Refractory Hodgkin Lymphoma and Outcome after Autologous Transplantation

IntroductionChildren and adolescents with Hodgkin lymphoma (HL) have excellent long-term outcomes after combined modality treatment, however ~15-20% will either relapse or have primary refractory disease. (Shankar A, BJH 2014) Salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard of care for many pediatric patients with relapsed HL.In adults, achieving a complete remission by functional imaging (FI), particularly positron emission tomography (PET), after salvage chemotherapy is a strong predictor of outcome after ASCT. The majority of published data in pediatric cohorts has employed computed tomography (CT) measurements to assess pre-transplant disease status. We report pre-ASCT FI and clinical outcomes of 49 consecutive children/adolescents, who underwent ASCT for relapsed/refractory HL at our institution.Patients and MethodsFollowing IRB approval, the records of 49 patients with relapsed/refractory HL who received ASCT from January 1, 2001 to December 31, 2014 were reviewed. All had PET (43) or gallium (6) at time of relapse and subsequent time points in disease evaluation pre-ASCT. Available PET scans were reviewed by 2 nuclear medicine physicians, blinded to the clinical data, and assigned Deauville scores. 12 patients who did not have available PET images had outside reports documenting negative PET upon completion of initial salvage therapy. Negative FI was defined as interval resolution of previous gallium avid disease, documented negative PET, or Deauville score ≤ 3.Relapse therapy regimens varied. Patients received standard conditioning regimen with carmustine, etoposide, cytarabine and melphalan(BEAM) followed by stem cell infusion. Post-transplant radiation therapy (RT) was given if no prior RT to the site(s) of relapse. Overall survival (OS) was measured from the date of transplant to death from any cause, progression free survival (PFS) defined as a relapse of HL, with non-HL-related deaths censored. (Lieskovsky JCO, 2004) OS and PFS distributions were examined using Kaplan-Meier curves and the differences between groups were analyzed using the log-rank test and a significant P value < 0·05.ResultsMedian age at time of transplant was 16.4 years; 55% of patients were males. Eighteen (37%) had refractory disease, 22 (45%) relapsed early (3-12 months from completion of primary therapy) and 9 (18%) relapsed late (>12 months).Thirty-one (63%) relapsed within initial RT field. First-line and salvage therapy regimens are detailed in Table 1. Fourteen (27%) received ≥2 salvage therapies; 3 had a 3rd line agent. Nine of the 14 (64%) later achieved negative FI. Three patients with positive PET after initial salvage therapy did not receive a 2nd line regimen. Pre-ASCT,41 patients (84%) had negative FI vs 8 (16%) with positive FI. Eighteen patients (37%) received post-transplant RT; including 5 (64%) in the positive FI group and 13 (32%) in the negative FI group. Median duration of follow up post-transplant was 45.6 months (1-180 months).Forty-five patients were alive and disease-free at last follow up. Post-transplant events included 2 early deaths from transplant-related complications, 1 motor vehicle accident and 1 relapse 6 months post-transplant (pre-transplant Deauville score of 5, death at 12 months). No patient developed a second malignancy. 3-year OS for entire cohort was 92% (95% CI 78-97) with PFS of 98% (95% CI 86-99). 3-year PFS was 100% vs 86% (95% CI 33-98) in negative and positive FI groups respectively (p=0.02). 3-year OS for negative and positive FI patients was 95% (95% CI 82-99) vs 75% (95% CI 31-93) respectively (p=0.06). Complete remission by FI after initial salvage therapy was associated with a trend in OS (97% vs 82% in those with persistent disease) (p=0.08) but not PFS. Extra-nodal disease at relapse, refractory disease and radiation-field relapse had no significant impact on either OS or PFS in a univariate analysis. Cox proportional hazard ratios could not be performed on multivariate analysis given rarity of events.ConclusionOur analysis revealed outstanding outcomes for children/adolescents with relapsed/refractory HL. Negative pre-ASCT PET or gallium was associated with excellent PFS and OS but there were too few relapses to identify the predictive value of pre-transplant FI. Patients who do not achieve complete metabolic response to second line salvage therapy may be candidates for novel approaches. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A risk-based approach to cancer surveillance after completion of primary therapy in rectal cancer.

e23089Background: For cancers with a high risk of recurrence, most guidelines recommend 5 years of surveillance after primary treatment in order to detect relapses that are still amenable to furthe...