bluuebunny/crossref_metadata_2025 huggingface dataset:
Next generation sequencing of cell free circulating tumor DNA in blood samples of recurrent and metastatic head and neck cancer patients.
Authors: Porter Ashleigh , Daniels Gregory A. , Patel Sandip Pravin , Sacco Assuntina Gesualda , Banks Kimberly , Cohen Ezra E.W.
Published: September 2018

e17516

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is an increasingly prevalent disease but effective targeted therapy is lacking. The use of next generation sequencing (NGS) in the identification of novel targets has been suggested as a way to potentially expand therapeutic options and thereby improve outcomes. Methods: Data was collected on patients with recurrent and metastatic (R/M) head and neck cancers who underwent molecular profiling of blood samples utilizing Guardant360, a 70-gene circulating tumor DNA (ctDNA) NGS platform. CtDNA sequencing data was compared to tumor NGS data, when available. Best response to therapy was assessed using RECIST measures. Results: 60 HNSCC patients were evaluated from February 2015 to June 2016. The most common tumor type and histology was oropharyngeal squamous cell carcinoma (n = 21), which was commonly human papillomavirus (HPV) positive (n = 15). Other cancer types included salivary gland and thyroid cancers. The most common mutations identified by ctDNA analysis were TP53 (98%), PIK3CA (43%), NOTCH1 (38%), and ARID1A (36%). These findings were consistent with results from tumor sequencing data (n = 29) where TP53 (48%) and PIK3CA(24%) were also reported with the highest frequency. Importantly, 73% (n = 22) of patients had alterations identified in ctDNA that were not present in tumor specimens. Actionable mutations were identified in 66% of HNSCC and in 50% salivary gland cancer patients. Of patients with actionable mutations, 10% (n = 6) received matched targeted therapy (MTT): 3 (50%) had stable disease (SD), 1 had progressive disease (PD), and 2 were not evaluated. Of those who did not receive targeted therapy (n = 23), 1 (4.3%) patient had a complete response treated with immunotherapy, 11 (47%) had SD, and 11 (47%) had PD. Conclusions: Analysis of ctDNA may play a role in management decisions in R/M HNSCC. The majority of patients had unique mutations identified on ctDNA. The utility of ctDNA NGS and its role in patient management should be explored in future studies.
Clinical evaluation of circulating tumor cells in locally advanced nasopharyngeal carcinoma: A prospective study.
Authors: Wu Yuan , Qian Yu , Peng Jun , Wei Xueyan , Yuan Zilong , Zhou Fuxiang , Hu Desheng
Published: September 2018

e17523

Background: Circulating tumor cells (CTCs) have been showed to correlate with curative effects and prognosis in many cancers, but there are few data describing the importance of CTCs in nasopharyngeal carcinoma (NPC). Our aim was to prospect the karyotyping of CTCs and the correlation between CTCs and clinical response in patients with locally advanced NPC. Methods: Serum was collected in 82 patients with locally advanced NPC. CTC was measured by negative enrichment with immunostaining of CD45, DAPI and imFISH with the centromere of chromosome 8 probe (CEP8) method. Cells with CD45-/DAPI+/CEP8 ≥3 were defined as positive CTCs and the karyotyping of chromosome 8 in CTCs were identified as triploidy, tetraploidy and multiploidy. Patients were treated with 2 cycles of induction chemotherapy followed by concurrent chemoradiotherapy according to the clinical trial (NCT 02562599). CTC was also measured after each cycle of chemotherapy. Clinial response was classified according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1) criteria. Results: Positive CTCs were detected in 42 of 82 patients prior to treatment. They were independent with age, sex, smoking and clinical stages. Continuous CTC detection of 30 enrolled patients with positive CTCs showed that the ratio of CTCs and CTCs with different ploidies significantly decreased after therapy (P < 0.05). Although the change was not correlated with clinical response (P = 0.054), the decreases in CTCs count of patients who had complete response (CR) to the treatment were significant (P < 0.05), while the decreases of CTCs count of patients who had partial response (PR) were not (P > 0.05). Further analysis indicated that CR patients had fewer tetraploidy CTCs prior to the therapy than PR patients (P < 0.05). Moreover, tetraploidy CTCs count also indicated a positive prediction value for clinical response to treatment according to maximum likelihood estimation (P = 0.045, 95%CI [1.032,18.060]). Conclusions: The decrease of CTCs is correlated with a better therapeutic efficacy in patients with locally advanced NPC and the number of tetraploidy CTCs before treatment could be used as a predictive factor for clinical outcomes.
The demography of human papillomavirus (HPV) infections in oropharyngeal cancer patients from 2011-2016: A single Veteran Administration institution.
Authors: Dawson George Anthony , Zhang Yue Hua , Laurio Angela , Smith Patricia , Dellatto Michael , Innis-Gordon Fiona T. , Reino Anthony
Published: September 2018

e17532

Background: Human papilloma virus (HPV) is a known biologic (viral) carcinogen and has a predilection for tissue in head and neck sites- HPV types 16/18. Current NCCN guidelines recommend HPV testing on newly diagnosed cancers - Head and Neck region - specifically the oropharynx. Methods: After IRB approval, data from our center ranging from 01/01/2011 to 12/31/2016 were collected by using international classification codes (ICD-9) 142, 143, and 146. We enrolled 81 patients for review from of these anatomic sites: Base of tongue, Tonsils, Posterior hypo-pharyngeal wall, soft palate and unknown primary + neck nodes. Data collected: HPV status / age / stage at diagnosis. Risk factors collected were marital status, ethnicity, age, alcohol and tobacco use, and other co-factors. Results: A total of 73 of 81 cases met our criteria for inclusion into review: excluded - 5 with Non-Hodgkin’s lymphoma; 1 with plasma cell neoplasm; 2 excluded - p16 testing only. All enrollees were male. Age range 45 - 91. Mean age: HPV + 64.11 / HPV – 66.76yrs. Anatomic site:BOT-35(48%) /Tonsil-25 (34%) /unknown primacy- 6(8%) /Soft palate– 4(0.05%) /Hypo-pharnyx-3(0.04%). Ethnicity: Non-Hispanic White– 32(44%) /Black-19(26%) /Hispanic – 20 (27%) /American Indian – 1(0.01%) /Unknown – 0. Seventy-three tested for HPV: 36 pos (49%) /37 neg (51% ). Whites were of 49% HPV+. HPV16/18+ in 34 of 36 (94%) tumors. Tobacco exposure ever:32/37(75%) HPV + and 26/36 (75%) HPV - groups. Alcohol use ever: HPV+ 75%; HPV – 67%. Location:BOT/Tonsils were 32/36 (80%) HPV+ cases and 27/37(73%) of HPV – cases. HPV + Marital status: Married 9 (26%) / Never mar 9/Divced 15/Sep 2/Wid 1 - 74% not married. HPV – 37: Married 12 (32%) /Never mar 9 /Divced 9/Sep 5/Wid 2 – 68% not married. Conclusions: HPV +16/18 (34 of 36) infections in our patients (73) were 49% of the overall group. BOT and Tonsil cancers most were the common sites in both groups (+/-). Compared to non-VA patients, our HPV + group used more alcohol and smoked more, and were older - though both groups (+/-) had high usage rates. We noted more divorcees, and lower marriage rate in the HPV+ group. Whites were 44% overall but 49% of HPV + group.
Computer extracted features of nuclear architecture in H&E sections to predict disease recurrence in oropharyngeal squamous cell carcinoma patients.
Authors: Lu Cheng , Lewis James , Madabhushi Anant
Published: September 2018

e17536

Background: Most patients with oropharyngeal squamous cell carcinoma (OPSCC) are cured of their disease but 10-20% will develop recurrence. Identifying high risk patients is key to tailoring therapy and reducing treatment-related morbidity. In this study, we present initial findings using computerized analysis of local nuclear architecture from digitized H&E tissue sections of OPSCC via a new algorithm called cell run-length features (CRF) to distinguish patients with more versus less aggressive disease. Methods: H&E stained tissue microarray sections of 160 primary p16+ OPSCC were digitally scanned. Our CRF analysis involved 1) nuclei segmentation, 2) creation of local cell cluster graphs based on proximity of nuclei, and 3) computing CRF for each cell cluster graph. The CRF reflects the total number of different ways/runs that the graph vertices can be traversed. A higher CRF reflects more complex nuclear spatial architecture, while a lower CRF reflects the converse. A series of CRF features relating to statistics of the graph runs across the image are then extracted,. The top 5 predictive features were identified via Wilcoxon Rank Sum Test and then evaluated in conjunction with a binary quadratic classifier via 5-fold cross validation. Results: The top ranked features were related to CRF non-uniformity (i.e. reflecting the variation of complexity of different nuclei clusters) and the classifier yielded a mean area under the receiver operating characteristic curve of 0.75 in discriminating patients who did and did not have disease progression. Patients with high risk CRF values were 5.7 times more likely to suffer disease recurrence than those without. While the whole cohort had a disease recurrence rate of 12.5%, those with low CRF values developed recurrence in only 1.875%. Conclusions: CRF features demonstrate a strong association with disease recurrence in patients with p16 positive OPSCC. Our preliminary findings suggest that measurements related to local arrangement of nuclei have potential in the risk assessment of patients with p16 positive OPSCC. The findings will need to be independently validated in a separate, powered cohort of patients.
Towards mapping immune responses of nasopharyngeal carcinoma in Saudi Arabian patients, single institution experience.
Authors: Al-Rajhi Naser , Soudy Hussein , Mohammed Shamayel , Khoja Hatem , Ghebeh Hazem
Published: September 2018

e17541

Background: The prevalence of Nasopharyngeal Carcinoma (NPC) is higher in Saudi Arabia compared to western countries. Genetic susceptibility and/or environmental factors (like infection with Epstein-Barr virus) contribute to the development of this tumor. There is a lack of information on the expression of markers related to the immune response in Saudi NPC patients. Methods: Here we report on profiling of two cohorts of NPC cases from patients treated at King Faisal specialist hospital & Research cneter (KFSH&RC) using the most relevant immune markers. The first cohort included 54 patients with local NPC while the other cohort included 25 cases of metastatic NPC at presentation. Immunostaining was done using Ventana benchmark fully automated system. Two anatomical pathologists (SM & HK) scored the NPC cases for CD3+ infiltrating lymphocytes (TIL), and their sub-fractions co-staining for CD8, FOXP3 and/or PD-1. On the other hand, PDL1 expression was assessed on tumor cells. Statistical analysis was done using JUMP Pro 13 software. Results: There was an induction of membranous PDL1 expression on tumor cells of 70 and 64% in local and metastatic cases respectively. Interestingly, there was a significant number of cases with cytoplasmic expression of PDL1 (46% of local and 36% metastatic cases) in addition to the membranous expression. PD-1 was over-expressed (on ≥ 10% of TIL) in 52% and 68% of local and metastatic cases respectively. FOXP3+ T-cells were abundant in the tumor tissues as 78% of cases had ≥10% of their infiltrating CD3+ T-cells co-staining for nuclear FOXP3. Finally, CD8 were an abundant fraction of total CD3+ infiltrating T-cells in more than 60% and 78% of Local and metastatic cohorts respectively. Correlation of the above studied immune markers with patients clinical outcome shows statistically significant correlation (p = 0.008) between low CD3+ T-cell infiltration in tumor tissues at diagnosis and the relapse of the disease. Conclusions: PDL1 is upregulated, FOXP3+ T-regs are abundant, only the low intensity of CD3+ lymphocytes could predict for higher chances of relapse. These preliminary profiling data provide the basis for future immunotherapy trials for NPC in KFSH&RC
The impact of chronic hepatitis C virus infection on survival in oropharyngeal cancer patients.
Authors: Economides Minas P. , Sturgis Erich M. , Amit Moran , Hosry Jeff , Mahale Parag , Jiang Ying , Torres Harrys A.
Published: September 2018

e17556

Background: An association between Hepatitis C virus (HCV) infection and oropharyngeal cancers (OPCs) has been reported; however, the clinical significance of this epidemiological finding remains unknown. We therefore analyzed the oncologic outcomes of HCV-infected patients (pts) with OPCs. Methods: In this retrospective cohort study, all pts with OPCs seen at MD Anderson (1/2004-12/2015) were reviewed. HCV infection was defined as detectable HCV RNA in serum. Risk of 5-year (yr) overall survival (OS) and progression-free survival (PFS) was compared between HCV-infected (HCV+) and uninfected (HCV-) pts. OPCs that were positive for p16 by immunohistochemistry were considered HPV-related. Antiviral therapy (AVT) included either interferon (IFN)-based or IFN-free regimens. Multivariate cox proportional hazards model was used to identify independent predictors of mortality. Results: We studied 161 pts. Most of the pts were white (141; 88%), male (132; 82%) and had tumor stage 3 or 4 (147; 92%). The OPC involved tonsils (83; 52%), base of tongue (67; 42%) or soft palate (11; 7%). The median follow-up time after OPC diagnosis was 3 yrs (range: 1-13 yrs). HCV+ (n = 25) and HCV- pts (n = 136) were comparable in regards to smoking and alcohol status. In univariate analysis, HCV+ pts had more OPC progression after 1stline cancer treatment (48% vs 20.6% in HCV-, P = .0009) and were more likely to relapse (26% vs 5% in HCV-, P = .02). In multivariate analysis, HCV was associated with increased all-cause mortality [hazard ratio (HR): 2.15, 95% confidence intervals (CI): 1.08-6.85; P = .02] and risk of OPC progression [HR: 5.42, 95% CI: 2.64-11.14; P = .0008] independent of age and cirrhosis status. In HPV+ OPCs (n = 86), HCV + and HCV- pts did not have significant difference in mortality [HR: 2.03, 95% CI: 0.82-4.98; P = .12]. AVT was administered after OPC diagnosis in 8 of the 25 HCV+ pts (32%), with 6 of them receiving IFN-free AVT. HCV+ pts that received AVT had better 5 yr OS (median of 5.2 vs 2.3 yrs, P = .005) and PFS (median of 3.1 vs 0.7 yrs, P = .007) than the ones who did not. Conclusions: HCV seems to affect the oncologic outcomes of pts with OPCs and treating this infection might be beneficial. HCV screening and treatment should be considered in such pts.
Clinical experiences of gene therapy.
Authors: Li Longjiang
Published: September 2018

e17561

Background: Based on the theoretic and clinical development of modern medicine, gene therapy has been a promising treatment strategy for cancer and other patients. Methods: In the present paper, we reviewed the history and clinical experiences of gene therapy from the aspects of treatment protocol, administration cycle, dosage calculation and evaluation of therapeutic effects, in order to provide more information for the further development of this promising treatment. Results: Although the development of gene therapy has not gone smoothly since the beginning of the clinical trials, the results showed that this was a promising treatment for the cancer patients. There are still a lot of researches needed to be done to further solve the theoretic and clinical issues, and to improve the therapeutic effects. Conclusions: : In conclusion, although the development of gene therapy has not gone smoothly since the beginning of the clinical trials, the results showed that this was a promising treatment for the cancer patients. There are still a lot of researches needed to be done to further solve the theoretic and clinical issues, and to improve the therapeutic effects. But the future of the gene therapy will be bright, and it will become a new basic strategy to help more patients.
Is there a role for adjuvant radiation in T1N0 squamous cell carcinoma tongue with adverse pathological features? Factors affecting local control and the development of a scoring system.
Authors: Srinivasalu Vijay Kumar , Subramaniam Narayana , Balasubramanian Deepak , Low Hubert , Anand Adharsh , Thankappan Krishnakumar , Philip Arun , Iyer Subramania , Pavithran Keechilat
Published: September 2018

e17565

Background: The patterns of recurrence and the prognostic factors of early tongue lesions have been previously described in literature, often grouping T1 and T2N0 tongue lesions together. Adverse pathological features (APFs) have been used to predict nodal spread, but the prognostic factors predicting local recurrences in T1N0 tongue have seldom been described. We aim to evaluate the APFs associated with poor local control and the possible need for escalation of therapy. Methods: A retrospective analysis of 144 patients of pT1N0 squamous cell carcinoma tongue, extracted from our database of 598 patients of oral cavity who underwent wide local excision with neck dissection in a single institution between 2006-2014 were included in our study. Patients who received any adjuvant therapy were excluded. Results: APFs associated with local control were least margin 5 mm (p=0.004), infiltrative margin (p=0.403), depth ≥ 4mm (p=0.136), lymphovascular invasion (p=0.301) and perineural invasion (p=0.342). We derived a scoring system assigning a score to each of these factors out of a total 10 points, based on the hazard ratio for local failure. Patients with a score ≥ 5 points had a 5-year local control rate of ≤ 60%. Conclusions: Having least margin of 5 mm was the greatest predictor of local failure. This would suggest that all patients having a margin of 5 mm need revision, however if they do not have additional APF (score ≤ 4 points), they still have good local control rates (5-year local control rate of 88%) and may be observed. Those who have margins over 5 mm with a total score ≥ 5 may still benefit from adjuvant therapy for local control. Those with margins over 5mm have improved local control rates (p=0.029). [Table: see text]
Long-term result of out-patient intra-arterial chemotherapy in patients with stage II and III oral cancer.
Authors: Ohmae Masatoshi , Kato Itsuro , Fujita Yusei , Tkaoka Hiroo , Meshii Noritoshi , Takasu Ayako , Nakazawa Mitsuhiro
Published: September 2018

e17569

Background: We have developed a superselective intra-arterial chemotherapy (iaCT) approach for oral cancer, in which intra-arterial catheter is retrogradely inserted via the superficial temporal artery and/or occipital artery. The extra-arterial portion of catheter is connected to an infusion reservoir implanted subcutaneously around the mastoid process through the subcutaneous tunnel. The catheter and reservoir are completely placed under the skin, so there is little possibility of catheter-related issues such as infection and displacement. Hence, out-patient iaCT (op-iaCT) can be performed. This method has improved ADL of patients without any loss of curative effect and oral function. We reported the usefulness of op-iaCT at the ASCO annual meeting in 2013. We assessed the long-term outcome and survival rate of patients with stage II and III oral cancer who received op-iaCT and survived for at least 5 years. Methods: We have used op-iaCT for 46 patients who had oral cancer, out of which we selected 14 patients with stage II and III oral cancer, and monitored them for more than 5 years. Results: Two patients died owing to distant metastasis, to the brain and liver, and 12 patients were cancer-free. Neck metastases were detected after primary treatment and op-iaCT in 3 patients, who were salvaged by neck dissection. The 5-year survival rate was 86%. Conclusions: Distant and/or regional lymph node metastases were observed in 5 out of 14 patients. The op-iaCT improves quality of life of patients with stage II and III oral cancer, but the metastasis rate is somewhat high. Close observation, intravenous chemotherapy, and /or prophylactic neck dissection should be employed in the op-iaCT approach for oral cancer.
Outcomes in patients with head and neck squamous cell carcinoma (HNSCC) requiring salvage resection after definitive therapy.
Authors: Haque Sulsal , Riaz Muhammad Kashif , Hassan Sarah , Karivedu Vidhya , Ying Jun , Takiar Vinita , Wise-Draper Trisha Michel
Published: September 2018

e17572

Background: Salvage surgical resection is often offered in HNSCC patients who develop locally recurrent disease after definitive therapy. However, survival outcomes are often poor and subsequent recurrence is frequently fatal. Patients with adverse pathological features (extracapsular extension (ECE) of lymph nodes (LN), positive margins, peri-neural spread, lympovascular invasion, multiple LN metastases) after primary surgical resection have been shown to have poor outcomes. It is unclear if these same features affect outcomes in surgical salvage patients. Therefore we conducted a retrospective analysis to analyze outcomes and potential risk factors in these patients. Methods: We analyzed forty-five patients at the University of Cincinnati from 2008-2014 that underwent salvage surgery after definitive radiation with or without chemotherapy. Independent categorical variables analyzed were age, gender, alcohol, smoking, time to relapse after definitive therapy and adverse pathological features. Dependent variables were relapse free survival (RFS) and overall survival (OS) censored at time of event or last follow-up visit. Kaplan-Meier curves were used to estimate RFS and OS and Cox Proportional Hazard models were used to assess hazard ratios between groups. Results: Median age was 57 (range 41 to 86). 75.6% of patients were male. 68.9% patients had adverse pathological features. Median OS was 59 months and median RFS was 38 months from surgery. Demographics and adverse pathological features did not affect survival. However, patients who relapsed after definitive therapy within 6 months vs. after 6 months had worse OS (See Table 1). Conclusions: Although adverse pathological features correlate with poor outcome in primary surgery, these features did not impact outcomes after salvage surgery in our population. However, patients who relapsed within 6 months of definitive therapy and underwent salvage resection had significantly worse outcomes than those who developed recurrence after 6 months. [Table: see text]
Inferring the effects of concurrent chemotherapy with or without adjuvant chemotherapy versus radiotherapy alone in stage II-IVB nasopharyngeal carcinoma: Comparison of results from meta-analysis of observational studies and randomized trials.
Authors: Tan Teng Hwee , Soon Yu Yang , Cheo Timothy , Tey Jeremy Chee Seong , Tham Ivan Weng Keong
Published: September 2018

e17573

Background: Multiple randomized trials (RCTs) reported that concurrent chemotherapy (CCT) with or without adjuvant chemotherapy (AC) improves survival in stage II-IVB nasopharyngeal carcinoma (NPC) compared to radiation therapy alone. However, it is unclear if similar benefits can be observed in routine practice as patients included in RCTs could be very different from patients in routine practice. The aim of this study is to compare the effects of CCT with or without AC as estimated from observational studies (OBS) with findings from RCTs. Methods: We searched MEDLINE for eligible studies determining the effect of addition of CCT with or without AC in stage II-IVB NPC. Outcome of interest was overall survival (OS). We performed the meta-analysis with random effects model to estimate the pooled hazard ratios (HR), confidence intervals (CI), and I squared statistic (I2) for both RCTs and OBS and compared them using Altman interaction test. Results: We found nine RCTs and 19 OBS including 6523 patients. Eight RCTs and 14 OBS had at least 75% of its patients with stage III-IVB NPC while only one RCT and five OBS had at least 75% of its patients with stage II NPC. The survival benefit associated with chemotherapy was similar in both RCTs and OBS focusing on stage III-IVB NPC (RCTs HR 0.67, 95% CI 0.56 – 0.81, I2 = 48% vs OBS HR 0.71 95% CI 0.62 – 0.82, I2 = 4%, interaction P (IP) = 0.67). Similarly, there was no significant difference in OS for RCT and OBS focusing on stage II NPC (RCTs HR 0.34, 95% CI 0.17 to 0.66, I2 = non-applicable due to single study vs OBS HR 0.61, 95% CI 0.37 to 1.02, I2 = 0%, IP = 0.17). Conclusions: Patients with stage II and stage III-IVB nasopharyngeal carcinoma treated in routine practice received similar survival benefits associated with concurrent chemotherapy with or without adjuvant chemotherapy as patients treated in randomized trials.
The Compassionate Use Advisory Committee (CompAC) for development of pre-approval access to investigational drugs.
Authors: Mitchell Edith P. , Caplan Arthur , Bateman-House Alison , Ray Amrit
Published: September 2018

e18001

Background: In May 2015, CompAC was formed at NYU to provide guidance fairly and transparently on allocating a limited supply of , Daratumumab, to patients outside of clinical trials. Janssen, manufacturer of Daratumumab, was receiving numerous pre-approval requests for access to the drug. Daratumumab (Darzalex) was approved in the U.S. for treatment of patients with multiple myeloma who have received at least one prior therapy and approved by EMA for monotherapy. The SPR program was phased out based on country level approvals, with requests and submissions managed in a regulatory and legal environment.Methods: CompAC was 10 medical experts, bioethicists, and patient advocates; ethical and medical principles for review and process guidelines developed. Weekly meetings were held to consider SPR requests, with 3 members voting each week. After U.S. approval, requests for drug were considered only from countries where Janssen was seeking but had not gained approval. Recommendations were conveyed weekly for final decisions. Results: A total of 331 cases were received by Janssen of which 5 withdrew and 2 expired, leaving 324 cases for review. Of these, 180 were sent to CompAC and 163 were recommended by CompAC for treatment. Janssen approved all 163. CompAC recommended declining 17 of these cases; Janssen declined 15 (2 cases were approved based on additional information provided). Of the 144 patients excluded by Janssen before CompAC review, 27 were due to low benefit/risk profile, 17 provided incomplete clinical information, 42 for other variables, 46 received alternative therapies, 10 for referral to another pre-approval access channel, and 2 commercially available drug. Of the cases that CompAC recommended declining, 11 were due to low benefit/risk profile, for 3 alternative therapies available, and remaining 3 for miscellaneous reasons. Requests were received from 13 countries, the majority from outside the U.S.Conclusions: CompAC was successfully implemented and provided rapid review of SPR requests for pre-approval Daratumumab access. Janssen is extending CompAC to other relevant assets. Other companies are considering the model.
Studying chemotherapy toxicity levels in district cancer care delivery model.
Authors: Pendharkar Dinesh , Tripathi Chandramavli M. , Aagre Suhas
Published: September 2018

e18003

Background: To increase the access to cancer care an innovative delivery model has been initiated in 77 district general hospitals of India , empowering general duty medical officers and offering 24x7 technology based backup. All the districts along with other care also offer chemotherapy services. Major concerns raised by medical community were of toxicity associated with administration of chemotherapy. Methods: Data from chemotherapy patients undergoing chemotherapy over short period of three months in one of the district hospital was collected using proforma and common terminology criteria for adverse events(CTCAE v. 4).Data was recorded in all patients by personal interview and clinical examination when patient reported for next c0urse of chemotherapy and during the administration. Results: Total number of 196 patients (136 female and 60 male) taking chemotherapy in district were evaluated. Majority of them had breast( 92), lung (24) head and neck cancer(18).A total number of 285 cycle in all lines –first, second, etc were administered. In breast cancer majority cycles were of adjuvant chemotherapy. Chemotherapy regimens in use included all standard combinations of Doxorubicin cyclophosphamide, docetaxel ,carboplatin , 5FU, paclitaxel . Commonest toxicity included nausea , vomiting, fatigue, diarrhea and anemia. Nausea was commonest (181 events)followed by vomiting (179) diarrhea (122) fatigue, anemia and neutropenia. Most toxicity was grade 1 and 2 only. Only 3 cases of febrile neutropenia were reported and there were 3 emergency admissions for vomiting ,diarrhea. No patient had to be shifted out for medical emergency to higher center. Conclusions: The level of toxicity in peripheral center matches that of standard toxicity levels reported in literature .It is feasible to safely manage chemotherapy at peripheral centers with training generalist and offering distant supervised care. For achieving universal health core goals, with extreme shortage of oncology personnel and services specially in in LMIC only such models appear to be feasible and practicable.
Time trends in the use of surgery for stage I non-small cell lung cancer (NSCLC) and the impact on population survival: Analysis from the Surveillance, Epidemiology, and End Results (SEER) Program.
Authors: Tran Krystel , Benjamin John , Woodford Katrina , Nardone Louise , Martin Catherine , Senthi Sashendra
Published: September 2018

e18013

Background: Surgery is the standard of care treatment for stage I NSCLC. Improvements in surgical techiques and perioperative care over time are developed to facilitate surgery for more patients. We assessed the factors influencing the use of surgery, the interaction of these with time and the impact on population survival. Methods: Patients enrolled into SEER between 2004 and 2012, aged at least 18 years with a first malignant primary stage I NSCLC were retrospectively assessed. Patients diagnosed on the basis of autopsy or death certificate only were excluded.Time was catergorized into three periods; 2004-6, 2007-9 and 2010-12. Age, gender, marital status, race, geographic location and time were all considered exposure variables influencing surgical use and were adjusted for using logistic regression. Impact of variables with time was assessed using interaction terms between them. The impact of time on population survival was assessed using cox regression. Results: Sex, age, marital status, race, location and time all significantly influenced whether surgery was performed (all p < 0.001). The proportion undergoing sugery declined from 68.0% during 2004-6 to 62.7% during 2010-12 (adjusted HR 0.88, p < 0.001 between subsequent periods). Patients were less likely to have surgery with increasing age (adjusted HR 0.94 per year, p < 0.001) and if they were Black or Hispanic (adjusted HR 0.58, p < 0.001 and 0.87, p = 0.008 repectively) relative to Non-Hispanic Whites. There were significant differences with location. Relative to San-Fransisco-Oakland, the greatest adjusted differences were between Louisiana (HR 0.51, p < 0.001) and New Jersey (HR 1.57, p < 0.001). Age significantly interacted with time (p = 0.007). Surgical use declined from 75.5% during 2004-6 to 71.5% during 2010-12 when less than 75 years. For those older, the decline was greater, 55.3% to 46.5%. The risk of death declined with time (adjusted HR 0.94, p < 0.001 between periods). Conclusions: Since 2004, the use of surgery for stage I NSCLC has declined and done more so with increasing age. Despite this overall population survival has improved.
Predictors of survival in patients with gastrointestinal malignancies admitted to the intensive care unit.
Authors: Ko Heidi Chwan , Yan Melissa , Gupta Rohan , Song Juhee , Kebbel Kayla , Maiti Abhishek , Nates Joseph L. , Overman Michael J.
Published: September 2018

e18050

Background: Cancer patients have a high use of healthcare utilization at the end of life which can frequently involve admissions to the intensive care unit (ICU). We sought to evaluate the predictors for outcome in gastrointestinal (GI) cancer patients admitted to the ICU for non-surgical conditions. Methods: The objective of this study was to determine the factors associated with ICU mortality, hospital mortality and overall survival (OS). A total of 200 patients with GI cancer admitted to the ICU at The University of Texas MD Anderson Cancer Center between November 2012 and February 2015 were retrospectively analyzed. Cancer characteristics, treatment characteristics, and Sequential Organ Failure Assessment (SOFA) scores defining severity based on 6 organ systems with scores ranging from 0 to 24 were analyzed for their effects on survival endpoints using multivariate logistic regression models and a multivariate Cox proportional hazards regression model. Results: The characteristics of the 200 patients were: 64.5% male, mean age of 60 years, median admission SOFA score of 6.0, and tumor types of primary intestinal (37.5%), hepatobiliary/pancreatic (36%), and gastroesophageal (GE) (24%). The ICU mortality was 26%, hospital mortality was 41%, and 6-month OS estimate was 25%. In multivariate analysis, ICU admission SOFA score > 10 (odds ratio (OR) 17.1, p < 0.0001), poorly differentiated tumor grade (OR 3.2, p = 0.02), and shorter duration of metastatic disease (OR 2.3, p = 0.07) were associated with increased odds of ICU mortality. These same variables were associated with increased odds of hospital mortality. In multivariate OS analysis, SOFA score 6-10 (hazard ratio (HR) 2.1, p = 0.0006) and SOFA score > 10 (HR 4.4, p < 0.0001), patients with GE primary (HR 2.2, p = 0.002) and patients with a poor outpatient performance status that precluded active chemotherapy (HR 2.2, p = 0.01) were associated with increased risk of death. Conclusions: The SOFA score was the most predictive factor for ICU mortality, hospital mortality, and OS for GI cancer patients admitted to the ICU. It should be utilized in all GI cancer patients upon ICU admission to improve both acute and longer-term prognostication.
Equity in access to tyrosine kinase inhibitors among veterans diagnosed with renal cell carcinoma.
Authors: Lynch Julie Ann , Lynch Kristine E. , Filipski Kelly Kristin , Berse Brygida , Rivera Donna , Chang Ji Won , Becker Daniel Jacob , Efimova Olga , DuVall Scott
Published: September 2018

e18051

Background: Tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes of advanced renal cell carcinoma (RCC) patients, although complete remission is uncommon. Disease-specific survival in RCC varies by race/ethnicity, but race is not an independent predictor of survival within single-payer healthcare systems, pointing to the importance of access to treatment. We analyzed patient-level utilization of three TKIs (sunitinib, sorafenib, and pazopanib) among veterans with RCC. Methods: In this retrospective cohort study, we used data from Department of Veterans Affairs (VA) Corporate Data Warehouse to identify veterans diagnosed with RCC from 2006 to 2015 and exposed to TKIs, and to obtain their demographic and clinical information. The distribution of patients’ characteristics across treatments was evaluated using chi square and t-tests. Results: Of 2,410 patients exposed to TKIs, 956 (40%) received more than one TKI. Sunitinib was prescribed to 1,761 (73%) patients, pazopanib to 766 (32%), and sorafenib to 600 (25%) patients. The use of sorafenib declined steadily over time, from 37% of patients diagnosed in 2006 to 2% of those diagnosed in 2015, while the use of pazopanib grew from 8% to 38%, respectively. The comparison group were unexposed patients in Stage IV RCC (N = 1,144). Patients exposed to targeted treatments were significantly younger at diagnosis than those with no exposure (mean [M] age 65 years, SD 9 vs. m = 70 years, SD 10; p < 001). There were no statistically significant racial/ethnic or gender differences between patients exposed and unexposed to TKIs. Exposed patients had significantly higher body mass index (BMI) than unexposed (M = 29.6, SD 6 vs m = 27.9, SD 6, respectively; p < 0.01). Receipt of TKI was positively correlated with both surgery and chemotherapy, and negatively correlated with Charlson comorbidity index (p < 0.01). Conclusions: We documented equal access to TKIs treatment within the VA among RCC patients of different ethnic backgrounds and gender. Treatment with TKIs was correlated with younger age and fewer comorbidities, but higher BMI. We observed trends in use of individual TKIs, with more recently approved pazopanib gradually replacing sorafenib and sunitinib.
An exploration of how a countries' HTA process can affect patient access.
Authors: Jaksa Ashley , Pontynen Anson , Bastian Alexander
Published: September 2018

e18052

Background: Drugs in the USA become available from the moment of FDA approval. Access to oncology therapies outside of the USA may be delayed by regulatory and additional payer HTA processes. This study aimed to examine differences in oncology conditions that may impact time from regulatory approval to an HTA reimbursement decision in countries with mandatory HTA. Methods: Oncology HTAs (N = 569) for medicines approved by the EMA, Health Canada, and the Therapeutic Goods Administration (Australia) were matched on indication with HTAs from France, Germany, Canada, England, Scotland, and Australia. Resubmissions were excluded. The date of the first reimbursement decision was subtracted from the date of the regulatory approval to determine the time to issue a reimbursement decision. Trends by disease were examined. Results: The time between regulatory approval and reimbursement decision was significantly longer for solid-state oncology drugs than for hematology oncology drugs (mean 344 days vs. 280 days, respectively; p = 0.03). Within hematology oncology, Non-Hodgkin’s Lymphoma had the shortest time to a decision (229 days; n = 37) while Myelofibrosis had the longest (411 days; n = 3). For solid-state diseases, Sarcoma had the shortest time (5 days; n = 2) and Small-cell Lung Cancer had the longest (752 days; n = 5) time to a decision. Conclusions: Time to patient access to oncology medications varies by disease condition, which may reflect disease-related factors that impact assessment. The time to a decision for a hematology medicine was approximately two months shorter than the time to a decision for a solid-state medicine. It is possible that unmet need, budget impact, or competitive features within hematology conditions are driving the speed of assessments in these medicines. Further research is needed to determine why there are differences in time to decisions by oncology disease conditions.
Disparities in resection of hepatic metastases in colon cancer.
Authors: Neuwirth Madalyn G. , Epstein Andrew J , Karakousis Giorgos , Mamtani Ronac , Paulson Emily C.
Published: September 2018

e18062

Background: Evidence suggests that resection of synchronous hepatic metastases (SHM) in Stage IV colon cancer is safe and can improve survival in select patients. Little is known, however, about the use of hepatic resection in this setting on a population level. Methods: A retrospective cohort study was performed of Stage IV colon cancer patients during 2000-2011 in SEER-Medicare data who had diagnosis codes confirming SHM. Univariate and multivariate logistic regression were used to identify patient factors related to receipt of hepatic resection. Results: There were 11,351 patients with colon cancer and SHM. 465 (4.1%) underwent surgical hepatic resection. The proportion increased steadily over time from 2000-2003 (3.5%) to 2009-2011 (5.1%) (p = 0.03). Patients who were older with higher comorbidity burden were less likely to undergo hepatic resection (Table 1). Additionally, the odds of hepatic resection were 30% lower for African-American patients than for white patients (OR 0.70, p = 0.05). Odds of hepatic resection were 44% lower for patients from ZIP Codes with > 20% poverty than for patients from areas with < 5% poverty (OR 0.56, p < 0.001). Interestingly, among patients who underwent no surgical treatment at all, only 12% saw a surgeon after diagnosis. This number increased over time from 7.7% in 2000 to 15.9% in 2011 (p < 0.001). Similar disparities noted above were seen with regard to being evaluated by a surgeon. Conclusions: Despite evidence supporting the safety and efficacy of hepatic resection in the setting of SHM, few patients are seen by surgeons and go on to receive hepatic surgery. Additionally, access to hepatic resection is notably lower for African Americans and patients from areas with higher poverty rates. [Table: see text]
Racial and social disparities on aggressiveness of end-of-life cancer care in a rural academic center.
Authors: Namireddy Praveen , Macherla Shravanti , McClain James Thompson , Muzaffar Mahvish
Published: September 2018

e18063

Background: Aggressive cancer care at the end of life (EOL) can impact quality of life and have major economic burden. The purpose of this study was to determine the aggressiveness of EOL cancer care, and its relation to race, gender and social factors in Eastern North Carolina with a high rural and minority population. Methods: This is a retrospective analysis of 401 stage 4 solid tumor patients who died between 2011 and 2014 at Vidant Medical Center. Aggressiveness of care was calculated by a composite score adopted from Earle et al. Scores range from 0 to 7 with higher scores indicating more aggressive EOL care. 1 point was given to each indicator of aggressiveness in the last 30 days of life: ED visits ≥2, hospital admissions ≥2, any ICU admission, hospitalized days ≥14, new chemotherapy, hospice care ≤ 3 days, and any chemotherapy in the last 14 days. Results: Among 401 patients, 217 (54%) were white and 178 (44%) were black. The mean composite score for aggressiveness (CSA) for whites was 1.18 and for blacks it was 1.87 (p<0.001). In the last 30 days of life, a higher proportion of blacks had ≥ 2 ED visits 28% vs 13%(p<.0001), ≥ 2 hospital admission 23% vs 13%(p=0.001), any ICU admission 29% vs 16%(p=0.0002), chemotherapy in the last 14 days 30% vs 20%(p=0.001), and ≥ 14 hospitalized days 35% vs 21%(p<0.001) compared to whites. More whites were enrolled in hospice compared to blacks 53% vs 45% (p<0.001). Correlation analysis using Fit Y by X model showed statistically significant differences between CSA (score ≤ 3 and >3) and other variables such as whites vs blacks p <0.001, females vs males p=0.0006, not married vs married p<0.0001, and no family support vs family support p<0.0001. Conclusions: Male, unmarried and black patients were associated with higher CSA. Patients who were white, married and with family support had higher likelihood of enrolling in hospice. [Table: see text]
PD-L1 expression profile and immunotherapy (IO) experience in African American (AA) and Hispanic (H) lung cancer (LC) patients: Addressing disparities at a minority-based academic cancer center.
Authors: Shum Elaine , Su Christopher , Zhu Changcheng , Gucalp Rasim A. , Haigentz Missak , Packer Stuart H. , Baker Cheryl , Eng Yoko , Ravera Elizabeth , Browne Royston , Perez-Soler Roman , Halmos Balazs , Cheng Haiying
Published: September 2018

e18073

Background: Immune checkpoint inhibitors have changed the treatment paradigm for metastatic LC. Minority populations are under-represented in large IO clinical trials. Among 989 pts with newly diagnosed LC at Montefiore Medical Center - a community-based academic center from 2014-2015, 330 (33%) were AA and 195 (20%) were H. In line with practice-changing clinical studies, PD-L1 expression testing and IO have been incorporated into LC treatment. Methods: Pts receiving IO and/or had PD-L1 testing between 1/1/14-12/31/16 were identified from records obtained from pathology, pharmacy, oncology clinics and Clinical Looking Glass. Retrospective chart review was conducted. PD-L1 testing was performed using 22C3pharmDx IHC. Results: We identified 111 pts with LC who received IO and/or had PD-L1 testing, with a median age of 66. 55% were female. Based on race, 52 (47%) were AA, 24 (22%) were White, 26 (24%) were Other, and 9 (8%) were race unknown. Based on ethnicity, 30 (27%) were H, 73 (66%) were non-H and 8 (7%) were ethnicity unknown. 82% were former/current smokers. Adenocarcinoma was the dominant histology (60%). The majority were EGFR WT (91%) and ALK neg (98%). PD-L1 testing was performed in 67 (60%), including 32 (29%) AAs and 20 (18%) Hs. Archival tissue was used in 63%. PD-L1 TPS > 50% was found in 30%, 1-49% in 24%, < 1% in 37%. 62 pts received IO, including 26 (42%) AAs and 18 (29%) Hs. Nivolumab was the most commonly used agent (77%). In AAs, 8 (31%) received IO as 1st line, 13 (50%) as 2nd line, 5 (19%) as 3rd line and above. In Hs, 1 (5%) received IO as 1st line, 10 (56%) as 2nd line, 7 (39%) as 3rd line and above. Immune-related adverse events (IRAEs) were reported in 31% of AAs and 39% of Hs. Data analysis on survival is ongoing. Conclusions: Unlike the low numbers of minority pts in large clinical trials, we found no significant difference in PD-L1 testing and IO across racial and ethnic groups treated at our center. Compared to large clinical trials, we observed lower rates of IRAEs in our cohort. Our current and ongoing observations in these populations may have future implications in narrowing health disparities based on race/ethnicity.
Long-term survival in chronic lymphocytic leukemia after first primary malignancy in the United States.
Authors: Bista Amir , Uprety Dipesh , Ghimire Subash , Giri Megha , Shah Binay Kumar
Published: September 2018

e18090

Background: There has been significant improvement in survival among patients with primary Chronic Lymphocytic Leukemia (CLL) in recent years but, not much is known about survival among CLL developed after a first primary malignancy. Methods: SEER 18 database, 2015 submission, was used to calculate 5 and 10 year relative survival (RS) by period survival modeling method for 1993 to 2012, with division of the period into 4 cohorts of 5 years each. SEER*Stat software from National Cancer Institute was used to calculate relative survival (RS) for 4 different periods of 5 years duration. The trend in survival for cases with CLL as second primary cancer (CLLSPC) was evaluated using COX proportional hazard method using Cansurv software and also compared with that of primary CLL cases. Results: A total of 8731 patients with CLLSPC were included in the study, which represents 14.5% of all cases of CLL. The median age at diagnosis was 75 years. Median time to diagnosis of CLL was 50 months after diagnosis of first primary malignancy. Prostate cancer, breast cancer and colorectal cancer were 3most common primary cancers. 5-year and 10-year RS improved significantly in the year 2008-2012 compared to 1993-1997 (59.3% to 70.2%,P 0.044 and 40.1% to 50.6%, p 0.045). In subgroup analysis, significant improvement in 5-year and 10-year RS was seen in females and ≥ 80 years age group but no significant improvement was observed in males and age group 60-79 years. Survival among CLLSPC was significant worse compared to first primary CLL in all periods, even after adjusting for age and sex. Conclusions: CLLSPC represents about 14.5% of all CLL cases. Relative survival among patients with CLLSPC is gradually improving but still lags behind that of CLL as first primary cancer.