bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular-based classification algorithm for endometrial carcinoma to categorize ovarian endometrioid carcinoma into prognostically significant groups.
Authors: Parra-Herran Carlos , Lerner-Ellis Jordan , Xu Bin , Bassiouny Dina , Cesari Matthew , Ismiil Nadia , Nofech-Mozes Sharon
Published: September 2018

e17081

Background: The Cancer Genome Atlas classification divides endometrial carcinoma in biologically distinct groups, and testing for p53, mismatch repair proteins (MMR) and polymerase ɛ (POLE) exonuclease domain mutations has been shown to predict the molecular subgroup and clinical outcome. While abnormalities in these markers have been described in ovarian endometrioid carcinoma (OEC), their role in predicting its molecular profile and prognosis is still not fully explored. Methods: OECs resected in a 14 year period were retrieved. Only tumors with confirmed endometrioid histology and negative WT1 were included. POLE mutational analysis and immunohistochemistry for p53, MLH1, MSH2, MSH6 and PMS2 was performed in formalin-fixed, paraffin-embedded tissue. Following the molecular classifier proposed for endometrial carcinoma ( B J Cancer 2015;113:299-310), cases were classified as: POLE mutated, MMR abnormal, p53 abnormal and p53 wild type. Clinicopathologic information was recorded including patient outcome. Results: 73 tumors were successfully reviewed and tested. Of these, 8 (11%) were POLE mutated, 6 (8%) were MMR abnormal and 17 (23%) were p53 abnormal; the remaining 42 cases (58%) were p53 wild type (no POLE, p53 or MMR abnormalities). Mean follow-up period was 69 months (median 62, range 1-179). The molecular classification was an independent predictor for disease free and overall survival on multivariate analysis (p = 0.005 and 0.045 respectively, Cox proportional hazard model). POLE mutated and MMR abnormal groups had 100% 5 year DFS and OS. p53 wild type cases had intermediate survival rates (86% DFS and OS). Conversely, the p53 abnormal group had worse outcomes with 42% DFS and 76% OS at 5 years. Conclusions: OEC can be classified into prognostically distinct subgroups by testing for molecular surrogates, akin to endometrial cancer. MMR and POLE alterations seem to identify a subset of ovarian endometrioid carcinomas with excellent outcome; conversely, abnormal p53 expression carries a worse prognosis. In the era of personalized medicine, the use of these markers in the routine evaluation of ovarian endometrioid tumors should be considered.
Comprehensive molecular profiling of advanced gynecologic malignancies.
Authors: Rojas Luis , Williams Casey B. , Starks David , Williams Kirstin Anne , Leyland-Jones Brian
Published: September 2018

e17082

Background: Precision medicine has been studied in patients with advanced, heavily-treated cancers by administering molecularly targeted monotherapies. Rational combination approaches that are selected based upon molecular analysis, tailored for each patient based upon their past medical history, performance status and unique molecular profile, and curated to prevent the development of resistance represent a possible solution that warrants further exploration. Methods: The primary aim of this proposal, Identifying Molecular Drivers of Cancer (NCT02470715), is to recognize genetic drivers of cancer by performing comprehensive genomic profiling (CGP) and/or proteomic characterization, and further translational research of patient samples. A molecular tumor board discussed results upon receipt and recommended customized combinations. Final decisions of implementation were the choice of the treating physician. Results: CGP was evaluable in 46/64 (72%) advanced gynecologic malignancies (GYN). The remaining 18 are either awaiting therapy or too early for evaluation. Thirty three/45 (73%) patients received combination therapy matched to the CGP. Fourteen/34 (41%) matched patients achieved CR, 12/34 (35%) achieved a PR, 6/34 (18%) achieved SD, and 2/34 (6%) had progression after 3 cycles. Clinical benefit rate was 94%. For ovarian cancer (25 pts), the response rate was 75% and the median progression-free survival (PFS) is 8.5 months and ongoing in 4 patients. Twelve/46 (26%) patients received CGP, but were treated with standard treatments because of insurance denial or inability to get drugs. Two/12 (17%) achieved a CR, 3/12 (25%) achieved SD, and 7/12 (58%) had progression. The PFS for patients that received standard therapies was 1 month. Median number of prior therapies in all patients was 4. Conclusions: Management of advanced gynecologic malignancies with customized combinations of approved agents based on the patient’s tumor CGP was feasible, resulted in superior therapeutic outcomes and improved PFS compared to standard therapies in heavily pretreated controls within this cohort. This precision oncology therapeutic model for gynecologic malignancies deserves prospective large scale evaluation. Clinical trial information: NCT02470715.
Adjuvant carboplatin and paclitaxel chemotherapy followed by radiotherapy in high-risk endometrial cancer: A retrospective analysis.
Authors: Colombo Bonadio Renata RC , Azevedo Renata Gondim Meira Velame , Harada Guilherme , Miranda Vanessa Costa , Ferreira Patricia Alves de Oliveira , Freitas Daniela , Filho Elias Abdo , Gabrielli Flavia , Estevez-Diz Maria Del Pilar , Costa Samantha Cabral Severino da
Published: September 2018

e17115

Background: It remains unclear which is the best chemotherapy (CT) regimen and what is the role of adding radiotherapy (RT) to adjuvant CT in high-risk endometrial cancer. Methods: We performed a retrospective analysis of the patients (pts) with high-risk endometrial cancer (endometrioid histology stages III-IVA or carcinossarcoma/ clear cells/ serous histology stages I-IVA) treated with adjuvant carboplatin (AUC 5) and paclitaxel (175 mg/m2), every 3 weeks, for 6 cycles, followed by RT (conformal external beam radiotherapy to pelvic or pelvic and paraortic fields with 45Gy-54Gy plus weekly vaginal brachytherapy with 20Gy in 4 fractions). Pts were treated from 2010 to 2016 at a Brazilian public cancer center. Medical records were reviewed for demographic, clinicopathologic and outcome information. Data was analyzed for overall survival (OS), disease-free survival (DFS), prognostic factors and toxicity. The Kaplan-Meier method was used for survival analysis and Cox proportional hazard model for prognostic factors. Results: 146 consecutive pts were evaluated. Median age was 62 years (range 35-81). Most patients had ECOG 0-1 (98%), endometrioid (53%) or serous histology (26%), grade 3 tumor (57%) and FIGO stage III (77%). Median follow-up was 26.5 months. The OS rates were 85% (95% CI 75 – 91%) in 3 years and 73% (95% CI 58 – 84%) in 5 years. Factors that significantly affected OS in a multivariate analysis were FIGO stage (p = .009), pelvic lymphadenectomy (yes vs no, p = .023) and positive peritoneal cytology (yes vs no, p = .002). 3-year and 5-year DFS rates were 79% (95% CI 70 – 86%) and 68% (95% CI 52 – 80%), respectively. The initial site of recurrence was limited to the pelvis in 3% of the pts, within the abdomen in 1% and extra-abdominal in 11%. Grade 3/4 AEs occurred in 47% of the pts and were mainly hematologic toxicity (43%). There were only 3 cases of febrile neutropenia and 4 cases of hospitalization due to toxicity. Conclusions: Our data suggests that adjuvant carboplatin and paclitaxel, followed by RT, in high-risk endometrial cancer is safe and effective. Low rates of pelvic recurrence were observed, which might be explained by the addition of RT to adjuvant CT.
Somatic tumor profiling of DNA mismatch repair (MMR) deficient endometrial cancers (EC).
Authors: Cadoo Karen Anne , DeLair Deborah , Mandelker Diana , Trottier Magan , Stewart Carolyn , Tran Christina , Kemel Yelena , Walsh Michael Francis , Scharf Felicia , Hyman David Michael , Joseph Vijai , Robson Mark E. , Abu-Rustum Nadeem , Offit Kenneth , Solit David B. , Berger Michael F. , Aghajanian Carol , Stadler Zsofia Kinga
Published: September 2018

e17121

Background: Approximately 20% of EC have loss of MMR ( MSH2, MSH6, MLH1, PMS2) protein expression by immunohistochemistry (IHC). The majority have somatic MLH1/PMS2 loss, driven by MLH1 promoter hypermethylation. For the remaining patients (pts), germline testing for Lynch Syndrome (LS) is recommended. However, half do not have a corresponding germline mut. This is considered “Lynch-like syndrome” (LLS) & clinical management is challenging. We sought to determine if tumor profiling could identify somatic mut potentially underpinning loss of protein expression. Methods: Per institutional standard, all EC, regardless of age or family history undergo reflex LS screening with IHC for MMR protein expression. Pts consented to IRB approved protocols. Tumor-normal sequencing was performed via custom next-generation sequencing panel (MSK-IMPACT). Electronic medical records were reviewed. Results: 16 pt have completed tumor sequencing, median age 53 (35-83), 6 (38%) < 50 yrs at diagnosis. 2 had personal history of additional cancer (DCIS, ovary), none had first degree relative with colon or EC. A mix of EC histologies was represented: 10 endometrioid (all grades), 2 clear cell, 4 mixed. There were no serous cancers. There were median 58 mut (9-546), 14 (88%) had hyper or ultra mutated EC. 5 EC were driven by somatic POLE mut (3 known hotspot, 1 likely pathogenic), all ultra-mutated phenotype, resulting in multiple somatic MSH6 muts with isolated IHC MSH6 loss. 4 EC had MSH2/MSH6 IHC loss with corresponding double somatic mut in MSH2. 5 had one somatic mut corresponding to the MMR protein loss, assessment of LOH in these cases is pending. Two cases are unexplained: 40 yo with IHC MLH1 loss, 47mut; 69 yo, IHC MSH6 loss, 12 mut. In this cohort of LLS, somatic muts were frequently observed in ARID1A (13,81%), PTEN (10,63%) & PIK3CA(9,56%), in keeping with non serous histologies. Conclusions: In line with our prior report that pt with LLS had benign personal & family cancer histories compared with LS pts, we have identified that in 56% of LLS EC either POLE mut or double somatic MMR mut likely underpins the MMR IHC loss. As such, in these LLS EC cases, somatic tumor profiling may help to rule out LS. Further testing is ongoing to increase cohort size.
Tumor volume as a prognostic factor in patients (pts) with locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) treated with induction chemotherapy (IC).
Authors: Palhares Daniel Moore Freitas , Batista Fernando Coutinho , Veneziani Ana Lima , Mattos Marcos Duarte , Mamere Augusto Elias , Capuzzo Renato Castro , Santos Carlos Roberto , Carvalho Andre Lopes , Viana Luciano De Souza , Jacinto Alexandre Arthur
Published: September 2018

e17507

Background: Tumor volume and the ratio of volumetric change have been demonstrated to have a prognostic role in head and neck cancers during definitive treatment in LAHNSCC. The aim of this study was to evaluate the prognostic value of tumor volume assessment during IC. Methods: We retrospectively assessed the tumor volume of 58 pts with LAHNSCC included in a prospective phase II trial which evaluated the safety of a non–5-fluorouracil-based IC (paclitaxel; cisplatin) followed by chemoradiotherapy (cisplatin; 70Gy/35fx) during 2009-2012. The volume of primary tumor (PrimV), all suspicious lymph nodes (LNV) and their sum (SumV) were determined on tomography before (CT1) and after (CT2) IC using a radiotherapy treatment planning system and the ratio of volumetric change was calculated for each variable (PrimV%, LNV% and SumV%). Results: The median follow-up time, the progression free survival (PFS) and the overall survival (OS) was 78,1, 19,3 and 22,5 months, respectively. Fifty-four pts were men, mean age 55,3±8,3y. Most had oropharynx (53%) and stage IV (72%) cancer. The median volume (cm3) was PrimV1= 25,5, LNV1= 7,5, SumV1= 40,7, PrimV2= 10,9, LNV2= 3,0, SumV2= 18,8 and median ratio of change (%) was PrimV% = 55, LNV% = 51 and SumV% = 54. Volume wa s associated with resectability (PrimV1, AUC ROC curve = 0,66, p = 0,04; LNV1, AUC = 0,85, p < 0,001; SumV1, AUC = 0,86, p < 0,001). Pts with SumV% reduction > 35% had better PFS (median 84,0 vs 10,1 months, 3y 52% vs 29%; HR = 0,39, p = 0,01) and OS (median 45,5 vs 17,0 months, 48% vs 21%; HR = 0,49, p = 0,04). On univariate analysis the PFS was correlated with T (p = 0,004), N (p = 0,01), stage (p = 0,03), primary site (p = 0,01), resectability (HR = 0,32, p = 0,001), PrimV1 (p = 0,002), SumV1 (p = 0,001), PrimV2 (p = 0,02), LNV2 (p = 0,04), SumV2 (p = 0,004), PrimV% (p = 0,04), LNV% (p = 0,003) and SumV% (p = 0,04) and OS was associated with T (p = 0,04), N (p = 0,02), stage (p = 0,04), primary site (p = 0,01), resectability (HR = 0,29, p < 0,001) PrimV1 (p = 0,003), LNV1 (p = 0,002) and SumV1 (p < 0,001). Conclusions: Tumor volume and the volumetric response during IC were associated with prognosis in LAHNSCC in the present study. Clinical trial information: NCT00959387.
Clinical behavior of stage IVC squamous cell carcinoma of the head and neck.
Authors: Wookey Vanessa , Kusi Appiah Adams , Kallam Avyakta , Ernani Vinicius , Smith Lynette , Ganti Apar Kishor
Published: September 2018

e17511

Background: Squamous cell carcinoma of the head and neck (HNSCC) with distant metastasis at diagnosis (stage IVC) is rare, and outcomes are often lumped together with those of patients who relapse following initial treatment. We evaluated prognostic factors in patients presenting with stage IVC HNSCC. Methods: Data was extracted from the National Cancer Database to determine prevalence, overall survival (OS), and prognostic factors of stage IVC HNSCC (oral cavity, gum, lip, oropharynx, tongue, tonsil and hypopharynx) in adults, using SAS software for analysis. OS curves were estimated using the Kaplan-Meier method and differences were compared using a log-rank test. Significant parameters in the univariate Cox proportional hazards regression model analyses were included in the multivariate model, and hazard ratios, p-values and 95% confidence intervals were presented. Results: Of 226,302 patients with HNSCC, 5458 had distant metastases at diagnosis (2.40%); 5238 had complete data and were included in further analyses. Median survival of the entire cohort was 9.07 months, and one-year survival was 41%. Age > 70 years, Black race and higher Charlson-Deyo comorbidity score were associated with worse OS, while HPV positive status, tonsil and tongue (not including base) primary, private insurance and receipt of any treatment were associated with improved OS on univariate analysis. In multivariate analysis, HPV positive tumors were associated with improved OS compared to HPV negative tumors (HR 0.63, 95% CI 0.48-0.82; p= 0.001), even after adjusting for site of tumor origin. Only patients with a Charlson-Deyo score of ≥2 had worse OS compared to those without comorbidities. Hypopharynx, lip, tonsil and base of tongue primaries had significantly worse OS compared to gum and other mouth. Except for radiation alone and radiation with surgery, treatment demonstrated significant improvement in OS compared to no treatment, a combination of chemotherapy, radiation and surgery provided the largest survival benefit (HR 0.23, 95% CI 0.20-0.28). Conclusions: HPV positivity seems to predict for better prognosis, regardless of site of origin. Patients with metastatic HNSCC should be offered multimodality therapy in order to improve outcomes.
Open label, non randomized, interventional study to evaluate response rate after induction therapy with docetaxel and cisplatin in unresectable locally advanced squamous cell carcinoma of head and neck (NCT02061631).
Authors: Zaidi S. H. Manzoor , Masood Ahmed I. , Shah Syed Ijaz Hussain , Hashemy Irfan
Published: September 2018

e17513

Background: This single arm, multicenter, phase 2 study was conducted to evaluate overall response (OR) rate and safety of subjects treated with induction regimen docetaxel + cisplatin, followed by chemoradiotherapy (CRT), in patients with locally advanced squamous cell carcinoma of oral cavity (stage III or IV) without distant metastasis. Methods: Induction regimen consisted of docetaxel 75mg/m2 and cisplatin 75mg/m2 on day 1; cycles were repeated every 21 days for 3 cycles with supportive G-CSF treatment beginning at first cycle. CRT consisted of weekly cisplatin 30mg/m2 for 4 weeks starting concomitantly with 60 Gy/30 fractions of conventional radiotherapy for 6 weeks. Primary and secondary efficacy criteria were OR rate at 3 weeks after cycle 3 and 8 weeks after last cycle of CRT respectively. Results: Three centers enrolled 35 patients. Primary efficacy endpoint: OR rate of evaluable patients (n = 27) was 88.9% (95% CI:71.9-96.2). Complete response (CR) was not achieved by any patients; partial response (PR) was achieved by 88.9% (24 of 27). From intent to treat (ITT) analysis OR rate was 68.6% (24 of 35). Secondary efficacy endpoint: OR rate of evaluable patients (n = 19) was 78.9% (95% CI:56.7-91.5) with CR and PR achieved by 2 (10.5%) and 13 (68.4%) patients respectively. Progressive disease (PD) was present in 4 patients. From ITT analysis CR rate was 5.7% (2 of 35) and OR rate was 42.9% (15 of 35). During induction most common hematological toxicity was leukopenia in 8 patients, with ≥Grade 3 leukopenia in 3 patients. Common non hematologic toxicities (all grades) were nausea, stomatitis and alopecia in 21, 18 and 18 patients respectively. During CRT most common adverse events were alopecia, stomatitis and nausea in 14, 13 and 13 patients respectively. Overall, leukopenia met seriousness criteria in 4 patients, and there was 1 case of febrile neutropenia. Overall, 7 patients died. Fatal events were not associated to investigational drugs. Conclusions: We observed an ITT response rate of 68.6% with docetaxel + cisplatin, suggestive of an active induction regimen with manageable safety profile. Clinical trial information: NCT02061631.
Relevance between PD-L1 expression combined with tumor infiltrating lymphocytes and prognosis in advanced hypopharyngeal squamous cell carcinoma.
Authors: Ono Takeharu , Azuma Koichi , Kawahara Akihiko , Sasada Tetsuro , Hattori Satoshi , Sato Fumihiko , Chitose Shun-ich , Shin Buichiro , Akiba Jun , Umeno Hirohito
Published: September 2018

e17528

Background: Little information has been available regarding immune-related prognostic factors in patients with advanced hypopharyngeal squamous cell carcinoma (HPSCC). Expression of programmed cell death-ligand 1 (PD-L1) in tumor cells is known to be a mechanism whereby cancer can escape immune surveillance. We investigated the predictive relevance of PD-L1 expression in tumor cells and tumor-infiltrating lymphocyte (TIL) density in patients with locally advanced HPSCC receiving neoadjuvant chemotherapy (NAC). Methods: We retrospectively reviewed 83 consecutive patients with advanced HPSCC who had received NAC. PD-L1 expression and TIL density were evaluated by immunohistochemical analysis. Results: Univariate and multivariate analyses demonstrated that CD8+ TIL density was an independent and significant predictive factor for progression free survival (PFS) and overall survival (OS), whereas PD-L1 expression was not correlated with PFS or OS. Subgroup analysis defined by PD-L1 expression in combination with CD8+ TIL density revealed that the PD-L1-/CD8high group showed the longest survival (median PFS and OS were not reached), whereas the PD-L1+/CD8low group showed the shortest PFS (median 7.9 months, p = 0.006) and OS (14.3 months, p = 0.011) by Kaplan-Meier curves. Conclusions: Although there was no significant correlation between PD-L1 expression and prognosis in stage III and IV HPSCC patients who received NAC, the subgroup analysis indicated that combination of lack of PD-L1 expression and higher CD8+ TIL density was significantly associated with favorable survival in these patients. These results suggested that PD-L1 expression levels in combination with CD8+ TIL density could be a useful predictive biomarker in patients with stage III and IV HPSCC.
Characteristics and outcomes of head and neck cancer in solid organ transplant recipients.
Authors: Alsidawi Samer , Price Katharine Andress Rowe , Chintakuntlawar Ashish V. , Garcia Joaquin J. , Westin Gustavo Figueiredo Marcondes , Okuno Scott H.
Published: September 2018

e17529

Background: The immune system plays a major role in anti-tumor surveillance in healthy individuals. Immunosuppression after solid organ transplant prevents graft rejection, but leads to increased incidence of various malignancies including head and neck squamous cell carcinoma (HNSCC). Outcomes of patients (pts) with post-transplant HNSCC are unknown. Methods: After Institutional Review Board approval, we retrospectively identified pts who developed HNSCC after solid organ transplant between 1995 and 2010. Adults with pathology-proven HNSCC and good follow up were included. Cutaneous cancers were excluded. Median overall survival (mOS) and progression free survival (mPFS) were analyzed using the Kaplan–Meier method. The prognostic effect of variables was studied with Cox proportional hazards models. Results: 33 pts met study inclusion criteria. The median time to HNSCC after transplant was 5.9 years. The primary site was the oral cavity in 15 pts, the oropharynx in 10, the larynx in 3, the hypopharynx in 2, the parotid in 2 and unknown in 1 pt. 58% of pts presented with locally advanced disease, 39% with localized disease and one pt with metastatic disease. 87% underwent upfront surgical resection. Of those, 66% received adjuvant therapy (38% radiation alone and 28% chemoradiation). 6% of pts had definitive chemoradiation. After a median follow up of 10.5 years, the 5-year OS rate was 45% and 37% for localized and locally advanced disease respectively. 75% of pts with oropharyngeal tumors were HPV-positive and they had better outcomes (5-year OS rate of 67%). The mPFS for the cohort was 22.8 months (95% CI; 11.6-50.1) with a median time to relapse of 15.2 months. The pattern of relapse was local in 69% of pts, distant in 25% and local plus distant in 6%. In a multivariate analysis, age > 60 years was a negative predictor of survival (HR 2.7; 95% CI, 1.1 to 6.5; P = 0.03). Conclusions: This retrospective study evaluated the clinical course and outcomes of pts with non-cutaneous HNSCC after solid organ transplant. Pts had inferior survival compared to historical controls. older pts had poor prognosis. The risk of local and distant recurrence was high. HPV-positive oropharyngeal tumors continue to have better outcomes in this population.
Tumor expression of hypoxia-inducible factor and antimicrobial peptides in oral fluid for prediction of after-surgery suppurative complications in patients with oral mucosa cancer.
Authors: Komarova Ekaterina , Kit Oleg Ivanovich , Kononenko Vladimir , Maksimov Aleksey Yurievich , Pozdnyakova Victoria V. , Novikova Inna Arnoldovna , Demidova Aleksandra
Published: September 2018

e17530

Background: It is believed that hypoxia-inducible factor (HIF-1α) hyperactivity promotes synthesis of protective factors and increases bacterial growth-inhibitory activity, provides enhancement methods of the congenital immune response to microbial infection. Methods: Lactoferrin and α-defensin were detected in saliva of 41 patients with oral mucosa (OM) cancer (T2N0-2M0) before a comprehensive treatment; enzyme immunoassay (EIA) method was used. A level of hypoxia-inducible factor (HIF-1α) was evaluated by EIA method in tumor tissues after surgical treatment. The patients were divided into two groups according to an after-surgery period: the main group (n = 16) had after-surgery suppurative complications. An after-surgery period proceeded without infectious complications in patients of a control group (n = 25). Results: It was found that Lactoferrin content in saliva statistically was significantly higher by 36,4% (p < 0,05) (3,0±0,24 µg/ml against 2,2±0,19 µg/ml) if to draw a comparison between the main group and the control group with respect to development of suppurative complications and absence of a inter-group difference according to α-defensin concentration (4,1±0,35 pg/ml against 3,8±0,19 pg/ml). HIF-1α expression index in the main group (8,4±0,79 CU/mg protein in a well) exceeded this index by 18,3% (p < 0,05) in the control group (7,1±0,79 CU/mg protein). A positive correlation between HIF-1α expression and Lactoferrin content (R = 0,53 at р = 0,0001) was detected in patients with OM cancer. Conclusions: Detected HIF-1α hyperexpression in tumor tissues and Lactoferrin content in saliva, as well as their interaction allows suggesting significance of these factors for their progression prediction in patients with OM cancer in case of after-surgery suppurative complications.
In-human activity and pharmacology of homemade silver nanoparticles in highly refractory metastatic head and neck squamous cell cancer.
Authors: Singh Jasmine , Fattah Farjana , Burks Tam , Zheng Jie , Jiang Xingya , Kurian Pamela , Saleem Sehresh , Pearson Jean , Khan Saad A.
Published: September 2018

e17533

Background: Silver nanoparticles (SNPs) show high efficacy as targeted therapy against cancer cell lines, but have never been tested in patient clinical trials. We present the first in-human trial of SNPs in a cancer patient with a dramatic outcome. Methods: Homemade SNP solution is prepared by the patient with online instructions. Current from 3 9-volt batteries is passed across 99.99% pure silver-bar electrodes in distilled water, until the metal content of the water measures 0.09-0.15 parts per million. The manufacturer is a 77-year old male who developed multiple recurrences of nasal cavity squamous cell cancer. Over 2 years he progressed on platinum and taxane based-chemotherapy, radiation twice and 2 surgical resections. Large hepatic and pulmonary metastases were observed on PET, MRI and CT; he was initiated on hospice. Without informing his oncologist he subsequently began manufacturing and consuming the SNP solution. Results: The patient ingested 120 ml daily of the solution for 3 months leading to clinical recovery and complete resolution of cancer at all sites, persisting for 18 months. Electron microscopy of the silver solution revealed bimodal SNP size distributions; 3 & 12 nm. Inductively coupled plasma mass spectrometry showed the basal blood silver ion concentrations of 32 ng/g. One hour after ingesting 60 ml of silver solution it rose to 46 ng/g. Urine showed no SNPs. Toxicities were not noted with this silver solution, with no evidence of myelosuppression, liver or kidney abnormalities on repeated testing. The patient underwent reconstructive surgery with excellent wound healing, and his performance status continues to improve. Conclusions: Ingestion of a SNP solution is associated with complete regression of highly refractory head and neck cancer in the absence of other anticancer therapy. Ingesting silver solution causes a noticeable and nearly immediate rise in blood silver concentration. Urinary excretion is not a major path of clearance from the body. Given these dramatic results that may be attributed to SNP in conjunction with strong preclinical data, further patient testing of SNP should be done to confirm its safety and efficacy in head and neck cancer.
Correlation of outcome with early metabolic response on FDG-PET in treatment of locally advanced nasopharyngeal carcinoma.
Authors: Kwong Dora Lai Wan , Lee Victor HF , Khong Pek lan
Published: September 2018

e17555

Background: Skull base changes often persist on CT and MRI after treatment in locally advanced nasopharyngeal carcinoma (NPC) and cannot be differentiated from active tumor. We prospectively evaluated the metabolic response of T3/T4 NPC during treatment with PET scans. Early metabolic response was correlated with outcome after treatment. Methods: 50 patients with T3/T4, N0-3, M0 NPC were recruited. All patients had 3 cycles of induction chemotherapy (IC, physician’s choice of regime) before concurrent chemoradiation (CRT) with cisplatin 100mg/sqm for 3 cycles. PET scans were performed before and after IC and at 30Gy of CRT. For primary tumor that showed complete metabolic response (mCR, defined as SUV max in tumor ≤1.25x liver background activity) on reassessment PET, the dose to tumor stopped at 70Gy. For those who did not achieve mCR, a boost dose was given to the residual tumor to total 76Gy. Results: On post-IC PET scan, 2 patients with extensive intracranial disease showed no response with static and progressive disease respectively and did not proceed to CRT. 48 patients showed regression of tumor and decreased metabolic activity on post-IC PET, 16 of whom achieved mCR. One patient with mCR after IC refused CRT. 47 patients proceeded to CRT. 44 patients had reassessment PET at around 30Gy and 25 patients had mCR during CRT. 47 patients who completed CRT were included in survival analysis. Median follow up after completion of CRT was 28 months. Among the 15 cases who achieved mCR after IC, all patients were disease free without relapse at time of analysis. Among the 32 patients who did not achieve mCR after IC, there was 1 persistent loco-regional disease, 1 local and 1 regional relapse and 6 developed distant metastases. The 3 year NP control, regional control, distant metastases free, progression free survival and overall survival were 89.4%, 96.9%, 79.5%, 49.2% and 81% respectively compared with 100% corresponding survival rates among patients who achieved mCR after IC. The difference in progression-free survival was statistically significant (p = 0.045) Conclusions: Early mCR was observed in 32% patient after IC and 56.8% of patients during CRT. mCR after IC predicts for very favourable outcome.
Evaluation of feasibility of preoperative concurrent chemoradiotherapy in locally advanced operable oral cancer and resection and reconstruction of mandibular/maxillary segment with prefabricated free fibular graft.
Authors: Deshmukh Sanjay P
Published: September 2018

e17558

Background: Every year more than 500,000 patients are diagnosed with oral cancer worldwide and majority require surgery and radiotherapy as a definitive curative treatment. Loss of bony segment of mandibular/maxillary bone with resultant loss of shape, function and ability to chew the food is known. Neoadjuvant chemoradiotherapy is known to have improved disease outcomes in many solid tumours. Methods: Total Seven patients underwent the planned protocol of 100 days. All patients were male and median age was 46 years. Six patients had disease involving lower alveolus and one had upper alveolus. All had no palpable nodes clinically. Step 1 a. Neoadjuvant treatment of Radiotherapy to Primary disease and draining lymph nodes dose of 45 to 50 Gy in 25 fractions over 5 weeks along with concurrent weekly Cisplatin 40mg/m2 for 5 cycles b. Mock surgery on 3D models with defining of insertion site of implants on fibular segment. Step 2 Insertion of dental implants in fibula and split skin graft in the desired fibular site in second week of radiotherapy. Step 3 Definitive surgery 6 weeks after completion of chemoradiotherapy and reconstruction by free fibular segment with primary dental prosthesis checking occlusion of oral bite. Results: Six patients(85.7%) are alive and free of disease at median follow up of 6.7 months. Three(42.8%) patients underwent prosthetic placement with acceptable outcome. Two patients had trismus and undergoing oral physiotherapy. Six patients had orocutaneous fistula. One had extrusion of fibular graft and one patient died. Five(71.4%) patients had complete response on final histopathology report and two had partial response. Conclusions: : A novel technique for better functional and aesthetic results with possible improved survival in operable oral cancer. Future randomized studies are needed for validation.
Outpatient intra-arterial chemotherapy without radiation therapy for stages II and III oral cancer: A new treatment to improve quality of life and reduce irradiation-related complications.
Authors: Ohmae Masatoshi , Kato Itsuro , Fujita Yusei , Takaoka Hiroo , Meshii Noritoshi , Takasu Ayako , Nakazawa Mitsuhiro
Published: September 2018

e17567

Background: We developed a superselective intra-arterial chemotherapy (iaCT) approach to oral cancer, in which an intra-arterial catheter is retrogradely inserted through the superficial temporal artery and/or occipital artery with concurrent radiation therapy (RT). This approach remarkably improves the curative effect, but it decreases patients’ quality of life (QOL) because of prolonged hospitalization, severe stomatitis, lifelong dry mouth, dysgeusia, and radiation osteonecrosis of the maxillo-mandibular bone. Methods: This study assessed our new outpatient iaCT (op-iaCT) approach involving a subcutaneous infusion reservoir without concurrent RT. We included 23 patients, 11 with stage II and 12 with stage III oral cancer, and they were treated with the op-iaCT approach without concurrent RT. Using this approach, the chemotherapeutic agent was intra-arterially administered at the Outpatient Chemotherapy Center of Rinku General Medical Center. Results: The response rate to this approach was 100%, and all patients had a complete response. Four patients with secondary regional lymph node metastasis underwent neck dissection. Twenty patients were disease-free without an irradiation-related complication, whereas 3 patients died of distant metastasis (2) or local recurrence (1). With the exception of ambulatory visits twice per week for 3 weeks, patients’ activities of daily living (ADLs) were mostly unaffected. Moreover, patients rarely complained of dry mouth or dysgeusia, and they were free from radiation osteonecrosis after cancer therapy. Additionally, they did not develop oral dysfunction related to radical operation. Conclusions: In this approach, the catheter is implanted subcutaneously; therefore, common catheter-related issues rarely occur, resulting in good maintenance of ADLs. Moreover, patients can avoid the side effects of RT. Consequently, patient’s QOL improves and medical expenses decrease. Thus, our new op-iaCT approach improves QOL and the curative effect in patients with oral cancer if their ambulatory and performance status is good.
Timing of percutaneous endoscopic gastrostomy (PEG) tube placement as supportive care in HNSCC patients (Pts) receiving concurrent chemoradiotherapy (CRT).
Authors: Lupak Oleksandra , Bazydlo Michael , Siddiqui Farzan , Chang Steven , Coniglio Bryan , Wang Ding
Published: September 2018

e17571

Background: Concurrent CRT with curative intent is the standard of care treatment for Pts with locally advanced or local recurrent head and neck squamous cell carcinoma (HNSCC). The CRT is associated with significant toxicities including nausea/vomiting, dysphagia and/or odynophagia, which prevent Pts from tolerating oral hydration and nutrition intakes. Treatment frequently leads to weight loss, renal injury and unexpected emergent care or hospitalizations along with therapy interruptions. This study is to determine the timing of PEG tube placement and its impact on the safety and tolerability from HNSCC patients receiving CRT. Methods: We retrospectively reviewed 413 electronic medical records (EMR), of which 335 of HNSCC Pts who had complete EMR during CRT period were included in this study. 127 of these 335 Pts (38%) required no PEG tube placement, 208 (62%) required PEG placement. The timing of PEG placement has been observed as two groups: 1) 109 Pts had PEG tube placement before initiation of CRT (Prophylactic Group PG); 2) 89 Pts had PEG tube during CRT period in reaction to a serious toxicity event (Reactive Group_RG). Logistic regressions were used to estimate the effect of PEG timing on Emergency Department (ED) visits, hospitalization, and experiencing treatment interruptions. Results: Our study showed that patients in PG demonstrated 43% less likely on their visiting ED or 42% less likely for hospitalization than Pts of RG with an odds ratio (OR) at 0.396 (95% CI: 0.165~0.952, p = 0.038) for PG over RG from toxicity-related therapy interruptions. Pts in PG also showed an OR at 0.40 from improving hypoalbuminemia over RG Pts (95% CI: 0.16~0.64, p = 0.001) which associated with 23% of chance of maintaining pre-CRT body mass index (BMI) for Pts in PG over those in RG. Conclusions: We observed the prophylactic PEG tube placement prevented unexpected ER visits and hospitalizations through reducing the risk of malnutrition and dehydration, which improved Pts in PG through the CRT with less therapy interruptions and preserved BMI, especially for those Pts of older age, pre-therapy dysphagia, hypoalbuminemia and receiving cisplatin in CRT.
Patterns of recurrence in patients with sinonasal undifferentiated carcinoma (SNUC) treated with multimodality therapy at a single center.
Authors: Rodriguez Cristina P. , Liao Jay Justin , Liu Andrew W. , Parvathaneni Upendra , Laramore George E , Humphreys Ian , Davis Greg , Martins Renato G. , Chamberlain Marc C.
Published: September 2018

e17575

Background: SNUCs are rare and without established therapeutic standards. This is a retrospective review of therapeutic outcomes in pts with SNUCs treated at our center. Methods: Data was collected retrospectively on pts with a confirmed diagnosis of SNUC treated at the University of Washington Medical Center. Demographic data, tumor/treatment characteristics,and dates of recurrence/progression and death were recorded. The Kaplan Meier method was used to estimate survival outcomes; the log-rank and Wilcoxon tests were used to explore associations of clinical characteristics with outcome. Results: Between 5/1992 and 11/2016, 32 pts were treated, 1 was excluded due to incomplete data. The median age was 52 (range 22-82) years, 14(45%) were female, 26(83%) were white, 17(54%) reported current or former tobacco use. One presented with distant metastases, 1 had T2N0 disease, and all other pts had locally advanced disease. Six pts had nodal involvement on initial staging, and 25 patients had T4 disease. Eleven(35%) pts had no skull base/CNS invasion, 7(22%) had skull base extension up to the cribriform plate, 13(42%) had extension beyond the cribriform plate and into the CNS. Twenty-one(67%) pts underwent surgical resection, 29(93%) underwent radiation(XRT) with a median dose of 70 (range 54-72) Gy, and 28(90%) received cisplatin based chemotherapy, with 24 of these given concurrent with XRT, 19(60%) were treated with surgery followed by chemoradiation. With a median 61 months of follow up, 15 pts have recurred, 10 of these recurrences occurred in local sites, with 6 having intracranial progression, 2 of which were leptomeningeal. The median time to progression was 15 months and median overall survival was 58 months . Any vs no tobacco use (58 vs 35 mo p = 0.8), was not predictive of overall survival. The presence of nodal disease (87 vs 7 mo p = 0.005), and CNS invasion beyond the cribriform plate (NR vs 14 mo p = 0.04) was associated with inferior median overall survival. Conclusions: Local/CNS recurrence was the predominant failure pattern in our pts. CNS invasion beyond the cribriform plate and nodal disease were associated with significantly worse survival.
Multifocality and Hashimoto’s thyroiditis as independent predictors of structural recurrence in a cohort of low risk intrathyroidal papillary thyroid cancer.
Authors: Pezzullo Luciano , Marotta Vincenzo , Chiofalo Maria Grazia , Gambardella Claudio , Bellevicine Claudio , Grasso Marica , Conzo Giovanni , Docimo Giovanni , Troncone Giancarlo , Sciammarella Concetta , Colao Annamaria , Faggiano Antongiulio
Published: September 2018

e17577

Background: Increasing incidence of thyroid malignancies is almost totally attributable to papillary thyroid cancer (PTC). Although all disease stages are involved, PTCs confined to the thyroid were those with the higher trend. The absence of dedicated randomized controlled trials makes challenging the management of these low risk PTC at different steps of the therapeutic process (extent of surgery, prophylactic central node dissection, and radio-iodine treatment). Thus, it is mandatory to set a prognostic system suitable for this clinical setting. We analyzed prognostic factors of structural recurrence in a large cohort of consecutive low-risk intra-thyroidal PTC. Methods: Multicenter retrospective study including pT1/2 PTC without any evidence of extra-thyroidal disease. The following parameters were considered: gender, age at diagnosis, histology, tumour size, multifocality, pathologically-proven Hashimoto’s thyroiditis (HT), and radiometabolic treatment (RAI). The parameters significantly associated with structural recurrence at the univariate analysis ( p < 0.05) were included in the multivariate analysis. Results: We included 284 patients (mean follow-up 6.3 yrs). At univariate analysis, parameters achieving significance were: age at diagnosis ≥ 45 yrs (p = 0.001, OR 0.04, 95% CI 0-0.72), microcarcinoma (p < 0.001, OR 0.02, 95% CI 0-0.39), multifocality (p < 0.001, OR 4.3, 95% CI 1.88-9.84), HT (p = 0.018, OR 0.33, 95% CI 0.13-0.86), and RAI (p = 0.002, OR 19.43, 95% CI 1.16-323.3). At multivariate analysis, only multifocality (p = 0.042, OR 2.52, 95% CI 1.03-6.16) and HT (p = 0.036, OR 0.34, 95% CI 0.12-0.93) revealed as independent prognosticators. Conclusions: Our data show that multifocality and HT should be considered as the main parameters for the decision-making of low risk PTC. Further studies are required. Note: We acknowledge Umberto Veronesi Foundation for granting Vincenzo Marotta with Post-doctoral Fellowship year-2017 Award.
Diagnostic performance of thyroid multimodal-imaging comprehensive risk stratification scoring (TMC-RSS) system in characterising thyroid nodules.
Authors: Mahajan Abhishek , Vaish Richa , Arya Supreeta , Sable Nilesh , Pande Shilpa , Paul Peter , Kane Shubhada , Chaukar Devendra , Chaturvedi Pankaj , Pai P. S. , Pantvaidya Gouri , Thakur Meenakshi , D'Cruz Anil
Published: September 2018

e17588

Background: A univocal ultrasound (US) classification system for characterising thyroid nodules is still lacking. The aim was to create an algorithm (TMC-RSS) using US features in combination with Color Doppler (CD), TIRADS, elastography (ES) and test its diagnostic performance. Methods: Analysis of prospectively collected data over 10 months. All studies were performed on single equipment using standard US protocol with TIRADS scoring. Gold standard was pathology. 340 nodules in 260 patients of which 316 nodules included for final analysis. 148 (46.8%) benign and 168 (53.2%) Malignant. TMC-RSS Multiple Logistic Regression Model. Malignant characteristics:Plus (+) 3 points for: ES score 3/4, malignant nodes. (+) 1 point for: Taller than wider, microcalcification, hypoechogenicity, solid composition, ill-defined margins, central +/- peripheral vascularity. (+) 0.5 point for: irregular halo, size > 1 cm. Benign characteristics:Minus (-) 3 points for: Purely cystic, ES score-1; (-) 1 point for: spongiform, comet tail artefact, complete halo. (-) 0.5 point for: peripheral vascularity. Final TMC-RSS Score calculated by addition of all the points. Results: Mean age was 47.3 yrs. Mean size was 2.3 +/- 1.5 cm. Diagnostic performance of combined US, ES, TIRADS and CD (sensitivity: 96%, specificity: 95%, PPV: 95%, NPV: 96%, kappa: 0.911) was significantly higher (p < .001) than either combination of US, TIRADS, ES, CD. On multivariate analysis all US features except taller than wider were independent predictor of malignancy (p < .01). TMC-RSS Model had 90% sensitivity, 89% specificity and 91% accuracy for characterising nodules. On the ROC curve the cut-off for best performance of TMC-RSS score was 5.75. The cumulative risk of malignancy based on TMC-RSS score was 2.4% for score < 3, 18% for score ≥ 3 - < 6 and 80% for score ≥ 6. Conclusions: The proposed TMC-RSS is easy-to-use, robust, reproducible and provides higher degree of confidence to a non-expert radiologist. It can be the first step in standardization of reporting lexicon to allow effective communication between the radiologists, pathologists, and clinicians; helping avoid unnecessary interventions.
Implementation of molecular testing for EGFR mutations and ALK rearrangement in lung adenocarcinoma in Brazil.
Authors: Palacio Sofia , Lopes Gilberto , Prado Edna
Published: September 2018

e18002

Background: Lung cancer is the leading cause of cancer death worldwide. In Brazil, cancer is the second most common cause of death and there were an estimated 27,330 new cases of lung cancer in 2014. Targeted therapies have changed disease prognosis and current clinical guidelines advocate for EGFR/ALK molecular testing for all patients with advanced-stage lung adenocarcinoma. Access to this testing is often limited in the developing world. In the case of Brazil, there is limited data regarding the frequency of testing and the changes in patterns of testing overtime. Methods: De-identified data was obtained from a commercial database that surveys approximately 2,000 cancer physicians in Brazil regarding practice patterns. On average 300 physicians responded to the survey, which is conducted every 6 months, and provided information on about 18,000 patients. Subsequently, we identified patients with lung cancer and calculated the frequency of testing for EGFR mutations and ALK rearrangement from 2011 to 2016. Results: 11,684 patients with lung adenocarcinoma were analyzed from 2011 to 2016. The frequency of testing for EGFR mutations increased significantly: 12.8% (287/2,228) in 2011, 34.4% (738/2,142) in 2012, 39.2% in 2013 (822/2,092), 43.9% in 2014 (866/1,972), 53.3% (1165/2,184) in 2015, and 58% (626/1,066) for the first semester of 2016. Testing for ALK rearrangement also increased noticeably over the same period: 0% in 2011 (0/2,228) and 2012 (0/2,142), 0.9% (19/2,092) in 2013, 2.99% (59/1,972) in 2014, 5.5% (121/2,184) in 2015, and 4.8% (52/1,066) for the first semester of 2016. Conclusions: To our knowledge this is the largest data analysis regarding changing practice patterns of molecular testing for lung adenocarcinoma over time in Brazil and Latin America. The frequency of testing for EGFR mutations and ALK rearrangement has increased over the last 5 years but is still below the current guidelines recommending that all patients with advanced disease be tested. Further understanding of the barriers to testing, will hopefully lead to national strategies for universal implementation of molecular testing.