bluuebunny/crossref_metadata_2025 huggingface dataset:
Endometrial cancer recurrence: Adjuvant high-dose rate vaginal brachytherapy (HDR) versus HDR with whole pelvic radiation.
Authors: Villella Jeannine A , Palaia Thomas , Chalas Eva , Patrick Patricia , Haas Jonathan A.
Published: March 2020

e15504

Background: Investigators hypothesize that patients with endometrioid carcinoma of the endometrium treated with adjuvant high-dose-rate vaginal brachytherapy (HDR) alone vs. HDR with whole pelvic radiation (WPXRT) have similar recurrence patterns. Methods: Patients reated with any adjuvant HDR between March 2005 and January 2011 were included retrospectively. Demographic, pathologic and treatment data was extracted from the medical record. These clinical data were compared among subjects receiving HDR only vs. HDR with 4500 cGy whole pelvic radiation using t-tests, Mann-Whitney tests, and chi-square analyses as appropriate. Results: One hundred eighty-six patients received adjuvant HDR. Fifty eight were excluded from analyses (46 based on non-endometrioid histology; 12 lost to follow-up). Among the sample of 128 subjects, 56 were treated with HDR only vs. 72 with HDR and WPXRT (43.8% vs. 56.2%, respectively). Subjects were similar in age, body mass index, and the existence of medical co morbidities. Of the 72 patients receiving HDR and WPXRT, 28 (38.9) were staged IA-IC, 28 (38.9) were staged as IIA-IIB, 11 (15.4%) were staged as IIIA-IIIC, 1 was staged as IVA-IVB (1.4%) and 4 (5.5%) was unstaged at diagnosis. Complications were similar between the groups. A total of 5 subjects experienced a recurrence, 1 who received HDR only vs. 4 who received HDR and WPXRT (1.8% vs. 5.6%, respectively, p=0.27). The subject treated with HDR was diagnosed with a grade 1 endometrioid carcinoma and had recurrence in the lung. Of the 4 subjects treated with HDR and WPXRT, 3 had recurrence in the vaginal cuff and 1 had recurrence in the peri-aortic lymph nodes. Conclusions: Recurrence was low among all subjects and did not differ among those who received HDR therapy only compared to HDR therapy with whole pelvic radiation. Investigators plan to conduct additional studies with a larger sample size to determine whether a difference in recurrence exists while adjusting for disease stage and total treatment dosage. If such confirmatory evidence is found, HDR brachytherapy alone may be a viable alternative to the additional radiation exposure of WPXRT in treating patients with endometrioid carcinoma of the endometrium.
Combinatorial treatment using CTO with paclitaxel or paclitaxel orotate in sc-implanted human OVCAR-5 ovarian tumor model.
Authors: Maxuitenko Yulia , Gorman Greg , Karmali Rashida A.
Published: March 2020

e15515

Background: Paclitaxel (PXL) was converted to paclitaxel orotate (PXLO). Different combinations of Carboxyamidotriazole orotate (CTO) and PXL or PXLO were first evaluated in female non-tumored athymic NCr-nu/nu mice to determine the tolerance of the combinations. The antiproliferative and antimetastatic effects of CTO are related to inhibition of receptor-operated calcium channel-mediated calcium influx. CTO can inhibit calcium sensitive signal transduction in the VEGF and the PI3K pathways, and inhibit FGF-2-induced tyrosine kinase. Methods: The antitumor effect of combinations was tested for: i) PXLO compared to PXL, ii) combinatorial effect of low (342mg/kg/dose) and high (513mg/kg/dose) doses of CTO (Q1Dx14, PO) with low (11.6 and 10mg/kg/inj, Q2Dx3/2 weeks, IV) and high (23.2 and 20mg/kg/inj, Q2Dx3/2 weeks, IV) respectively, doses of PXLO or PXL, against sc-implanted human OVCAR-5 ovarian tumor xenografts. Results: Results obtained in non-tumored mice show high PXLO plus CTO was better tolerated than high PXL plus CTO. In tumor bearing mice, oral CTO at doses of 513 or 342mg/kg/dose Q1Dx14 given alone resulted in slight inhibition of tumor growth, reaching statistical significance only when administered at a low dose (two tumor mass doubling: p=0.036 for 342mg/kg/dose). PXLO at 23.2 and 11.6mg/kg/inj. given alone inhibited tumor growth (p<0.001, 0.029, respectively). PXL at 20 and 10mg/kg/inj inhibited tumor growth (p<0.001 and 0.011, respectively). Since body weight loss was less with the orotate form of PXL, PXLO should be the preferred drug over PXL. Addition of oral CTO 513 or 342mg/kg/dose to PXLO 23.2 or PXL 20mg/kg/inj resulted in comparable tumor inhibition to PXLO or PXL alone. However, combination of PXLO 11.6 and PXL 10mg/kg/inj with CTO 513 or 342mg/kg/dose resulted in tumor inhibition suggesting that a low dose of PXL or PXLO may be combined with CTO to achieve tumor inhibition and to allow the use of the lower doses of PXL to reduce toxicity. Conclusions: Results suggest that PXLO is less toxic than PXL and CTO influences the sensitivity of PXL suggesting a role for combinatorial therapy with low doses of PXL and CTO in this ovarian tumor model.
A regimen of weekly nab-paclitaxel with weekly carboplatin in recurrent ovarian cancer: A retrospective analysis.
Authors: Rauthan Amit , Patil Poonam , Somashekhar S. P. , Zaveri Shabber
Published: March 2020

e15516

Background: The standard of care for patients with recurrent platinum resistant ovarian cancer is treatment with non cross-resistant drugs. Carboplatin retreatment is usually not an option in the platinum resistant population. Weekly paclitaxel has been tried in recurrent patients. But paclitaxel can cause hypersensitivity reactions due to its Cremophor based solvent. nab-paclitaxel being a nano-particle albumin bound paclitaxel is devoid of this toxictity. Also, it is thought that nab-paclitaxel may have a higher intratumoral uptake leading to enhanced anti-tumor action. We looked at a regimen using weekly carboplatin with weekly nab-paclitaxel in platinum resistantrelapsed carcinoma ovary who had failed multiple lines of treatment. Methods: We treated 10 patients with recurrent platinum resistant ovarian cancer with measurable disease with nab-paclitaxel 100mg/m2 on days 1,8,15 with carboplatin at AUC 1.5 on days 1,8,15 intravenously, repeated every 28 days for 4 cycles. All patients had received 3 or more lines of chemotherapy for recurrent disease. We looked for response rate, progression free survival and toxicities. Results: Three patients had complete response, 5 patients had partial response and 2 patients had disease progression. Median PFS was 6 months. There were no instances of paclitaxel induced hypersensitivity reactions. Two patients developed grade 3 neutropenia. One patient developed grade 3 thrombocytopenia. Three patients required blood transfusions. One patient developed grade 3 neuropathy. Conclusions: Weekly combination of nab-paclitaxel with weekly carboplatin is a safe and potentially active treatment in recurrent platinum resistant ovarian cancers who had failed multiple lines of treatment. Considering the efficacy and favorable toxicity profile, this weekly combination needs to be tested in a larger number of patients.
Engrailed protein: A cancer-specific marker in epithelial ovarian cancer.
Authors: McGrath Sophie , Annels Nicola E. , Madhuri Thumuluru Kavitha , Haagsma Ben , Larbi Emmanuel Douglas , Pandha Hardev S. , Michael Agnieszka
Published: March 2020

e15517

Background: Ovarian cancer is a common malignancy, accounting for 4% of all cancers and 5% of all cancer deaths in women in the Western world. Engrailed-2 (EN2) is a homeodomain–containing transcription factor that is essential during early development. It is dysregulated in a number of cancers and its presence in urine is diagnostic of prostate cancer. We have investigated its role as a cancer-specific marker in epithelial ovarian cancer (EOC). Methods: Ovarian tumours and normal tissue were collected from patients with epithelial ovarian cancer (EOC) and tested by semi-quantitative RT-PCR as well as by immunohistochemistry. EN2 expression relative to B-actin was calculated using the Livak comparative Ct method (2-DDCt). All slides were scored on a 0-3 scale based on intensity, by two independent assessors. Results: We examined 118 EOC specimens, of which 64 were tested by immunohistochemistry and 54 by RT-PCR. 89 (75.42%) were serous, 18 (15.25%) endometroid, 7 (5.93%) mucinous, and 4 (3.39%) clear cell tumours. Normal ovarian tissue was used as a control. 104 (88.14%) tumours expressed EN2 whilst 14 (11.86%) were negative. Of the EN2 positive tumours examined using immunohistochemistry, 28 (51.85%) strongly expressed the antigen (score of 2-3), whereas 26 (48.15%) were weakly positive (score of 1). Normal tissue did not express EN2 and this difference was statistically significant (p<0.05). There was no correlation with tumour type, grade and stage. EN2 expressing mucinous tumours showed improved overall survival (p=0.0253). There was no correlation for survival or PFS for other histological subtypes. Conclusions: EN2 is a cancer-specific marker in epithelial ovarian cancer. Further work is currently ongoing to evaluate its significance in ascites, blood and urine. We plan to further evaluate its role as a diagnostic biomarker by examining blood, urine, and ascites.
Uterine sarcomas: Analysis of clinicopathologic factors and treatment outcomes—A single institution experience in long-term disease control.
Authors: Go Mylene Sy , Wang Le , Styler Michael , King Stephanie
Published: March 2020

e15522

Background: Uterine sarcomas behave aggressively and are associated with poor prognosis. Carcinosarcomas was re-classified as more akin to endometrial adenocarcinomas. The objective was to analyze the survival outcomes of all uterine sarcomas treated with various combinations of chemotherapy, radiation, and lymph node dissections. Methods: 60 patients with proven uterine sarcomas were treated at Hahnemann Hospital from 2002-2011. Survival analyses in each treatment group were performed by Kaplan- Meier method Results: Among the 60 women examined, 51% were carcinosarcoma, 25% leiomyosarcoma, 20% endometrial stromal sarcoma, and 4% adenosarcoma. 27% presented with stage I disease, 20% stage II, 13% stage III, and 40% with metastatic disease at diagnosis. One third of the leiomyosarcomas and endometrial stromal sarcomas have advanced disease at diagnosis. Median survival of all patients was 26 months, 20 months for carcinosarcoma, 25 months for high grade endometrial stromal sarcoma, and a trend toward superior overall survival at 73 months for leiomyosarcoma. After surgery, 51% of patients mostly carcinosarcomas received carboplatin and paclitaxel as adjuvant chemotherapy and 66% of leiomyosarcomas received gemcitabine and docetaxel. However, the survival analysis showed no statistically significant benefit in disease progression free survival. On the other hand, 50% of patients were also treated with adjunctive pelvic external beam radiation and 21% received additional vaginal brachytherapy. Our results demonstrated a small but clear survival benefit after pelvic radiation therapy. Pelvic lymphadenectomy was performed in 55% of these patients and lymph node involvement was found in 30% of uterine sarcomas mostly carcinosarcomas. Survival analysis indicated that pelvic lymphadenectomy was associated with significant survival benefit. Conclusions: Size, stage, nodal involvement, and histology are independent prognostic factors. Complete cytoreduction followed by lymph node dissection, and radiation therapy offered a survival advantage than surgery alone. However, the role of adjuvant chemotherapy remains uncertain.
Outcomes of young patients (age younger than 40) with cervical cancer treated with (chemo) radiotherapy: A Japanese multi-institutional study.
Authors: Ariga Takuro , Niibe Yuzuru , Toita Takafumi , Kazumoto Tomoko , Eto Hidehiro , Suzuki Osamu , Kinoshita Rumiko , Tsujino Kayoko , Takemoto Mitsuhiro , Kodaira Takeshi , Yamashita Hideomi , Hayakawa Kazushige
Published: March 2020

e15533

Background: To analyze treatment outcomes of young patients (age: <40 years) with uterine cervical cancer treated with definitive (chemo) radiotherapy in Japanese institutions. Methods: The records of 118 patients (age: <40 years) with cervical cancer were reviewed retrospectively. The median age was 35 years (range: 24-39 years). Clinical FIGO stages were as follows: Stages 1b1/1b2/1b/2a/2b/3a/3b/4a/unknown in 6/9/2/6/40/2/49/3/1 patients, respectively. Median maximum tumor diameter was 5.5 cm (range: 2-9.2 cm). Forty-six patients (39%) had enlarged pelvic nodes (>10 mm in the shortest diameter). One hundred five patients had squamous cell carcinoma, and 13 patients had non-squamous cell carcinoma. Definitive radiotherapy consisted of high-dose rate intracavitary brachytherapy and whole-pelvis external beam radiation therapy. The cumulative linear quadratic equivalent dose (EQD2) was 64 Gy (range: 30-80 Gy) prescribed at point A. Concurrent chemotherapy was delivered in 95 patients (81%). Results: Within a median follow-up time of 35 months, 44 patients developed recurrence. Thirty-nine patients (33%) had pelvic recurrence only, four patients (3%) had distant metastasis only, and one patient had both pelvic and distant metastasis. The 5-year overall survival rate (OS) and local control rate (LC) of all patients were 62 % and 64 %, respectively. The 5-year OS for patients with disease stages 1b1/1b2/2a/2b/3/4a were 80%/89 %/100 %/75 %/40 %/0 %, respectively. The 5-year LC for patients with disease stages 1b1/1b2/2a/2b/3/4a were 100%/78%/50%/75%/51%/0%, respectively. Twelve patients (10%) suffered grade 3 or higher late radiation morbidity. Conclusions: Our results suggest that young patients (age: <40 years) with cervical cancer, especially in locally advanced stages (stage III and IVA), might have a worse prognosis than older patients when treated with definitive (chemo) radiotherapy.
Small cell carcinoma of the female genital tract: A single institution experience.
Authors: El-Gehani Faraj , Sun Julia , Kamal Muna , Pertschy Danielle , Joseph Kurian , Tonkin Katia , Ghosh Sunita , Pervez Nadeem
Published: March 2020

e15540

Background: Small cell carcinomas (SCC) of the female genital tract (FGT) are rare and there is no standard treatment strategy for managing these patients (pts). The objectives of this study are to report the clinical experience and management of pts with SCC of the FGT, treated at the Cross Cancer Institute, Edmonton, AB, Canada from 1982 to 2009. Methods: A retrospective chart review of all pts diagnosed with SCC of the FGT between 1982 and 2009 was undertaken. Data was collected on demographics, clinical and pathological characteristics, and patient outcomes. Results: Twenty-seven pts were identified with primary sites as follows: cervix 16 (59%), endometrium 7 (26%), ovary 3 (11%) and vagina 1 (4%). Median age at diagnosis was 53 years. Seventy-eight percent (21/27) had pure SCC; the rest had mixed histology. Seventy percent (19/27) were positive for at least one neuroendocrine marker. Overall, thirty percent (8/27) had limited stage (LS) disease; Seventy percent (19/27) had extensive disease (ES). Treatment of limited stage pts was 3/8 (38%) concurrent chemotherapy with radiation, 3/8 (38%) surgery, 1/8 (12%) chemotherapy alone and 1/8 (12%) radiation alone. For extensive stage pts, 6/19 (31%) treated with surgery with or without adjuvant chemotherapy, 4/19 (21%) concurrent chemotherapy with radiation, 2/19 (11%) palliative chemotherapy and 7/19 (37%) supportive care only. For relapsing pts brain was the site of first distant recurrence in three pts. Median survival for the entire cohort was 7.4 months (25.9 months for limited stage disease and 4.8 months for extensive; p < .0001). Conclusions: SCC of the FGT tract is aggressive with an overall poor prognosis. There is no standard of care for these pts and they are often treated according to local protocols based on data extrapolated from SCC lung cancer. Incidence of brain metastasis as the site of first relapse is relatively lower in FGT SCC, suggesting unclear benefit to prophylactic cranial irradiation.
Pelvic irradiation versus pelvic irradiation with concurrent chemotherapy followed by extrafascial hysterectomy in the treatment of locally advanced cervical cancer in Honduras.
Authors: Henriquez Cooper Hoover Rodyl , Chuang Linus T. , Cardenas Joel , Zelayas Pedro Guillermo
Published: March 2020

e15556

Background: Because of the lack of brachytherapy in Honduras, patients with locally advanced cervical cancer underwent extrafascial hysterectomy after upfront pelvic irradiation or pelvic irradiation with concurrent chemotherapy. Methods: We compared the effect of pelvic radiotherapy with that of pelvic radiation and concurrent chemotherapy with cisplatin in women with advanced cervical cancer. Between 2008 and 2011, 165 women with advanced cervical cancer confined to the pelvis (stages IB2 through IIIB) received either 70 Gy of radiation to the pelvis alone or with concurrent weekly cisplatin. Patients underwent subsequently extrafascial hysterectomy six weeks after completion of radiation therapy. Results: Of the 165 eligible patients, 90 (54.5%) patients received only pelvic radiation therapy, and 75 (45.5%) patients received pelvic radiation and chemotherapy. Squamous cell carcinoma was identified in 135 (82%) cases and adenocarcinoma in 30 (18%) cases. On the final hysterectomy specimen, 69 (77.8%) patients who received pelvic radiation had a complete clinical response with no residual diseases; there were 40 (53.3%) patients who received pelvic radiation and chemotherapy achieved a complete response (p<0.001). In the group of patients that were treated with pelvic radiation and chemotherapy, only 25 out of 75 (33.3%) patients received the required cisplatin on schedule. The complete clinical response rate of the 25 patients who received the complete course of pelvic radiation and chemotherapy was 80%. Conclusions: Treatment of locally advanced cervical cancer in low-resource settings is met with challenges including the lack of brachytherapy, and unpredictable availability of chemotherapy. Only 33% of patients that were treated with the intention of concurrent chemo-radiation were able to receive cisplatin on schedule. This resulted in a significantly lower response in the patients who were treated with pelvic radiation and chemotherapy. In settings where the availability of chemotherapy is not always available, primary pelvic radiation for advanced cervical cancer resulted in a better treatment response.
Neuroendocrine tumors of uterine cervix in Mexican women.
Authors: Flores Lucia Edith , Green Dan , Morales-Espinosa Daniela , Cetina Lucely
Published: March 2020

e15569

Background: Neuroendocrine tumors of the uterine cervix are rare, aggressive, and carry a poor prognosis. Most are small cell (SCNEC) and large cell (LCNEC). The limited knowledge of this neoplasm is based on small series due to the rarity of the diagnosis.There is a lack of information about NEC in Latin America. We describe both demographic and clinical characteristic of Mexican patients; and their multidisciplinary management in a reference center. Methods: We studied retrospectively clinical and histopathological variables of 33 women treated at the National Cancer Institute of Mexico from 1991 to 2010 with NEC. Patients were allocated into groups according to staging (Group 1 FIGO stages IB1 and IB2; Group 2 IIA-IVA, and Group 3 IVB). Results: Mean age at diagnosis was 50 y.o.; mean tumour size was 4.9 cm. There were 59.4% SCNEC and 40.6% LCNEC. Stage at diagnosis: IB1 15% (n=5), IB2 3% (n=1), IIA 18.2% (n=6), IIB 27.3% (n=9), IIIA 6% (n=2), IVB 27.3% (n=9). Common sites of metastases were lung and liver. The most common presenting symptom was transvaginal bleeding. In Group 1, 6/7 patients received multimodal management with surgery, chemoradiotherapy and induction or adjuvant chemotherapy. In Group 2, 12/17 patients received three modalities, 3/17 received only 2, due to comorbidty. In Group 3, 8/9 received 2 modalities. Patients with one treatment modality were those with disease progression. Cisplatin was used concurrently with radiotherapy; paclitaxel and carboplatin or etoposide and cisplatin were used for either induction or adjuvant settings. Disease free survival in months was: 50.3 (group 1); 23.1 (group 2), and 3.5 (group 3). Overall survival was: 68.5, 46.3, and 17.2 months, respectively. Main sites of recurrence were pelvis, mediastinum, lung, liver, central nervous system, pancreas, adrenal gland, bone and soft tissue. Conclusions: TheNational Cancer Institute of Mexico offers multidisciplinary treatment emphasizing local control after systemic therapy in both early and locally advanced disease; providing the most favourable disease-free survival and overall survival described. To our knowledge, this is the first report of NEC in the Mexican population, where carcinoma of uterine cervix represents yet an important public health issue.
Integration of neuropathy-sparing multimetronomic bevacizumab and multibiochemical modulation followed by regional consolidation and maintenance therapy for refractory ovarian cancer.
Authors: Bruckner Howard , Brandeis Alison Emily , Radjabi Amir Reza , Mull Ruslan , Stega Jeanetta , Hirschfeld Azriel
Published: March 2020

e15576

Background: In vitro disease models predicted advantages for use of 1/2-1/4 standard cytotoxic doses and selection of drugs each of which simultaneously interact with multiple drugs. Methods: Treatment (rx) combined 10mg/kg bevacizumab (B) q 2 weeks, cyclophosphamide (Cy) 400mg/m2 modified AC (Garcia Gyn Onc 05) with low dose GFLIP (carboplatin=P) P -/+ docetaxel (D) (Bruckner, ASCO 08). Regional therapy followed: +/- intraperitoneal, target directed or D+cisplatin, +/- or empirical HIPEC. To prevent further neuropathy, present in 8 of 10 pts, D was reserved for late addition (as needed) to create less than 0.5cm or otherwise “eligible for reduction surgery” tumors. Results: Overall S is 8/10 and 4/6 @ 6 and 12 mos. Two lead pts S at 18+ mos. 10/10 tumor marker responses (R); 9/10 objective R all with benefit. Patients (pts) had failed a median of 3 prior regimens and all had large rapidly worsening tumors during prior rx; 6/10 were considered “entirely untreatable.” There were no grade 4 complicated AEs, other than anemia. Epistaxis and HTN were minor, easily controlled AEs. Three deaths due to disease: One pt, PS3, refused surgery for a preexisting bowel obstruction and one, PS3, required weekly paracentesis and had sb obstruction. She relapsed after four mos OR. The third, PS4, pt was paracentesis and thorocentesis dependent and had a 6 mos OR. Median PFS is not yet reached. The lead pt, a 33yo third line, twice operated achieved a pCR in 4 mos, now stoma reversed, unmaintained for 14+ mos, following vaccine rx. Seven had OR without D; brief addition of D; brief addition of D produced 3/3 OR, a pCR, CR and PR. IRB provided prospective oversight of consent. Conclusions: This is an active multi-drug, in theory, anti BRCA rx, for very high risk and some otherwise “untreatable” pts. Simultaneous modulation of multiple drugs, both metronomically, six ways, (Cy-GFIC-D) and biochemically, up to five ways "each," 15 ways (5+4+3+2+1), is safe. Algorithms can offer cost savings (for B) by selecting a finite, short, “best” period for rx and then definitive, B free, consolidation rx. B driven response can create new windows of opportunity for test worthy multidisciplinary rxs.
Docetaxel, cisplatin, and 5-fluorouracil-based induction chemotherapy followed by concurrent chemoradiotherapy with cisplatin in locally advanced stage III and IV nasopharyngeal cancer.
Authors: Dane Faysal , Atasoy Beste Melek , Akgun Zuleyha , Yumuk Fulden , Cabuk Devrim , Teomete Mehmet , Basaran Gul , Turhal Serdar , Abacioglu Ufuk
Published: March 2020

e16015

Background: Concomitant chemoradiatiotherapy (CRT) is the standard treatment in locally advanced nasopharyngeal cancer (LANPC). We studied the activity and tolerability of docetaxel, cisplatin and 5-fluorouracil-based induction chemotherapy (IC) followed by concurrent CRT with cisplatin in LANPC. Methods: Between 2004 and 2010 a total of 33 (15 stage III, 18 non-metastatic stage IV) patients were included into this retrospective analysis. Median age was 51 (range, 19 to 75) years. Twenty-five patients were male. IC was planned for three courses in all patients. IC was consisted of docetaxel and cisplatin (DC) in 11 patients and fluoropyrimidine, dosetaxel and cisplatin (DCF) in 22 patients. G-CSF and ciprofloxacin were given prophylactically to all patients received DCF. 3D conformal radiotherapy (RT) was administered in conventional fractionation (2Gy/fr, 5 fraction per week) using 6-18MV photon energy and appropriate electron energies. Therefore, nasopharynx, level I-V and supraclavicular lymph nodes received 46 Gy (phase I) whereas, nasopharynx and clinically positive or initially bulky lymph nodes received 70 Gy (phase II). Cisplatin (75 mg/m2/21days) was administered during RT concomitantly. Results: Median follow up for surviving patients was 48 months. There was no progression after IC. Complete (CR) and partial responses (PR) were achieved in 6 and 23 patients in nasopharynx, respectively. We observed CR and PR in 19 and 13 patients in neck, respectively. All patients were given 3 cycles of IC. The dose of chemotherapy was reduced in 8 patients during IC. Sixty-six percent of the planned cisplatin dose could be given in the concomitant setting. In 11 patients, cisplatin was either reduced or permanently stopped. Thirty-one patients completed RT as planned. Five years PFS and OS rates were 65.5% and 72.2% respectively. Conclusions: In our LANPC patients, induction DC(F) chemotherapy followed by concomitant CRT was promising. This strategy should be evaluated in prospective studies.
Palliative chemotherapy in head and neck cancers: A tertiary care center experience with weekly paclitaxel and cetuximab.
Authors: Prabhash Kumar , Noronha Vanita , Joshi Amit , Patil Vijay , Juvekar S , Muddu Vamshi
Published: March 2020

e16028

Background: The concept of combination of paclitaxel and cetuximab is an intersesting prospect as both these agents have single agent acitivity, minimal toxicity and hold a biological rationale for combination. The aim of our study was to see the safety,efficacy and feasibility of administration of this combination in a outpatient setting. Methods: This was a retrospective analysis of the prospectively collected data, of patients offered weekly paclitaxel and cetuximab from May 2010-May 2011. The standard schedule of cetuximab along with 80 mg/m2 of weekly paclitaxel was administered till either disease progression or withdrawl of patient's consent. The toxicity profile was noted in accordance with CTCAE version 4.02 and response in accordance with RECIST criteria. SPSS version 16 has been utilized for analysis. Descriptive statistics are been presented and analyis of estimation of overall and progression free survival has been done with Kaplan-Meier survival method. Results: 42 patients with a median age of 52 years (35-81 years) were included. The KPS score was 60 in 1 (2.4%),70 in 11 (26.2%) and 80 in 30 patients(71.4%). Nearly half of our patients 22 (52.4%) had a primary in oral cavity. Except 3 (7.1%) patients rest all had received some form of previous treatment. The median event free period(EFP) from previous first line treatment was 231 days, it was below 180 days in 38.5% of patients. Best response observed was CR in 1 patient (2.4%), PR in 11 (26.2%), SD in 17 (40.5%) and PD in 13 (30.9%). Grade 3-4 skin changes were seen in 3 patients, grade 3-4 neuropathy was seen in 3 patients and there were no episodes of grade 3-4 gastrointestinal or haematological toxicity. The overall estimated median PFS and OS were 128 and 256 days. The median estimated PFS for patients with EFP less than 6 months versus more than 6 months was 115 and 165 days respectively (p = 0.132). Conclusions: The combination of paclitaxel and cetuximab was found to be safe, feasible and appears to be clinically beneficial.
Excellent long-term control in locoregionally recurrent radioactive iodine-refractory papillary thyroid cancer with the addition of external beam radiation therapy to maximal surgical resection.
Authors: Wilson William A. , Valentino Joseph , Gal Thomas , Sloan David , Ain Kenneth B. , Arnold Susanne M. , Brill Yolanda , Kudrimoti Mahesh R.
Published: March 2020

e16035

Background: Locoregionally recurrent radioactive iodine (RAI) refractory papillary thyroid cancer represents a small percentage of papillary thyroid cancers but is an aggressive disease with significantly lower survival rates. This retrospective review is our experience with these cancers treated with maximal surgical resection followed by external beam radiotherapy. Methods: 26 patients treated from 2001-2011 were eligible for review. After obtaining IRB approval, medical records were reviewed for clinical outcome. All patients had histologically proven recurrences that were negative on I-131 scans. All patients were maximally resected. All patients received external radiotherapy to the thyroid bed, bilateral cervical lymph node levels II-IV, level VI, and superior mediastinal nodes. 15/26 patients received intensity modulated, 9/26 patients received 3-D conformal, and 2/26 patients received Tomotherapy radiation treatment. The mean dose was 5790 cGy (range 5280-6800 cGy). Results: All histologies were papillary thyroid cancer with 4/26 exhibiting tall cell features and 1/26 diffuse sclerosing features. All patients had locoregional relapse in the cervical nodes (16/26) or in the mediastinum (5/26) or both areas (5/26). The mean pre-treatment thyroglobulin was 5.2 (range <0.1 to 599.1). The mean post-treatment thyroglobulin was 1.0 (range <0.1-5.2). Median follow-up was 55 months (range 7-123 months). 0/26 patients failed locoregionally. 2/26 patients failed distantly (lungs). 20/26 patients (77%) of patients had undetectable thyroglobulin at last follow-up. 4/26 patients had detectable thyroglobulin (2.5-16.9), but had not recurred on imaging. 2/26 required PEG placement during treatment, but 0/26 patients were PEG-dependent on long-term follow-up. 1/26 patients experienced grade III osteoradionecrosis of the mandible. Conclusions: External beam radiotherapy provides excellent locoregional control for locoregionally recurrent radioactive iodine-refractory papillary thyroid cancers. Long-term grade III and IV toxicities are uncommon.
A prospective phase II study of induction chemotherapy and nimotuzumab for resectable locally advanced head and neck squamous cell carcinoma.
Authors: Zhao Xiaoying , Guo Ye , Zhu Yongxue , Wang Yu , Zhu Guopei , Hu Chaosu , Ji Qinghai
Published: March 2020

e16039

Background: We incorporated nimotuzumab, a humanized monoclonal antibody against the epidermal growth factor receptor (EGFR), into the induction chemotherapy for resectable locally advanced head and neck squamous cell carcinoma (LAHNSCC), aiming to evaluate the efficacy and toxicity of this novel combination. Methods: In this single-institute, prospective phase II study, patients with histologically confirmed and potentially resectable (T2-4, N0-3, M0) LAHNSCC were treated with induction therapy of nimotuzumab (400 mg day 1, cisplatin 75 mg/m² day 1, and 5-FU 750 mg/m² days 1-5) for 2 cycles. Radical surgery or radiotherapy/chemoradiotherapy was used as subsequent local therapy. The primary endpoints were overall response rate and pathological complete response (pCR). Results: Of 40 enrolled patients, 25 had stage IV disease and 20 had N2-3 node involvement. The most common tumor primary was hypopharynx (40%) and 9 patients had an oropharyngeal carcinoma. After induction therapy, the overall response rate was 87.2% and 24 patients got a T or N downstage. Twenty-seven patients underwent radical surgery and pCR was found in 4 patients (14.8%). After surgery, 25 patients received adjuvant radiotherapy or chemoradiatherapy depending on the risk factors. For responding patients after induction, radiotherapy, usually concurrently combined with high-dose cisplatin was given to 12 patients as local therapy with a median dose of 60 Gy. One patient with stable disease after induction refused surgery and was treated with second-line chemotherapy in an attempt to pursue organ-preservation. There were no more than 10% of grade 3/4 toxicities induced by induction therapy. Only one patient experienced with mild rash. One patients developed grade 2 renal dysfunction after first cycle and chose immediate surgery. With a median follow-up time of 13.9 months (3.8-29.9), 1-year progression-free and overall survival rate were 80% and 83.3%, respectively. Conclusions: For resectable LAHNSCC, nimotuzumab plus chemotherapy as an induction therapy is highly effective with tolerable toxicities.
Base of tongue squamous cell carcinoma susceptibility: Novel candidate genetic polymorphisms identified in genome-wide association study.
Authors: Lima Carmen Silvia Passos , Carvalho Benilton , Pellegrino Renata , Khater Leticia , Chone Carlos Takahiro , Costa Fernando Ferreira , Lourenco Gustavo Jacob
Published: March 2020

e16041

Background: Inherited genetic alterations, such as single nucleotide polymorphisms (SNPs), were described in association with oropharyngeal cancer risk in few reports with restrict number of SNPs analyzed. Base of tongue (BT) squamous cell carcinoma (SCC) is a common tumor of oropharynx; however, the association of SNPs and BTSCC risk is not clarified and, therefore, this was the aim of this study. Methods: DNA from 49 BTSCC patients and 49 controls was extracted using the QIamp kit (Qiagen). Each sample was genotyped individually using DNA high-resolution microarrays containing 500.568 SNPs (SNP array 5.0, Affymetrix). Further sample processing, including digestion, adaptor ligation, amplification, fragmentation, labeling, hybridization, washing and scanning was assayed according to the standard protocol. Genotype data were acquired by genotyping calling of samples using crlmm algorithm provided by Bioconductor software. The differences between groups were analyzed by the logistic regression model. The SNPs localized in genes of interest were selected by data base analysis in DAVID and NCBI websites. The validation of selected SNPs was performed by RT-PCR, using TaqMan SNP Genotyping Assays (Applied Biosystems) in all samples studied. Results: We observed 6.609 SNPs with distinct frequencies between BTSCC patients and controls. Fifty-two SNPs (0.8%) were located in coding sequence (CDS), 51 (0.8%) in 3’ and 5’- untranslated regions (UTR), 3.461 (52.4%) in up or downstream regions (DWS) and 3.045 (46.0%) in introns. Ten SNPs were selected and validated in study, including those localized in genes related to cell cycle (3’-UTR: ERP29, rs7114; MCC, rs7033; DWS: LEF1, rs2107028 and rs4245926; PTCH1, rs16909856 and rs16909859), transcription process (CDS: IKBKAP, rs3204145; 3’-UTR: ZNF415, rs3814), and cell adhesion (CDS: COL22A1, rs2292927; DWS: LY6K, rs1995467). Conclusions: Our preliminary results suggest that SNPs in genes involved in tumor development may predispose individuals to BTSCC. However, these results should be confirmed by functional protein studies and validated in larger epidemiological studies. Financial support: FAPESP and FINEP.
Induction chemotherapy with docetaxel, cisplatin, and 5FU (TPF) in unresectable advanced head and neck squamous cell carcinoma: Retrospective analysis of 300 cases and proposal for a prognostic index.
Authors: Bozec Alexandre , Fakhry Nicolas , Dupuis Charlotte , Lallemant Benjamin , Alfonsi Marc , Benezery Karen , Righini Christian , Guelfucci Bruno , Beltran Michel , Borchiellini Delphine , Poissonnet Gilles , Dassonville Olivier , Schori Clara , Giovanni Antoine , Peyrade Frederic
Published: March 2020

e16055

Background: Phase III studies have demonstrated that induction chemotherapy with TPF followed by cisplatin-based chemoradiation (CRT) is a valid option for the treatment of advanced unresectable head and neck squamous cell carcinoma. These studies have been done in highly selected patients. The aim of our study is to confirm these data in unselected patients and to identify prognostic factors of tolerance and survival. Methods: Between October 2005 and June 2010, 300 patients from 5 institutions with locally advanced neck and head cancer received at least one induction cycle, followed by locoregional radiotherapy (R) associated or not with platinum (P) or cetuximab (C)-based chemotherapy. Results: Mean age was 56 years old (range 31-76). Performance status was 0 or 1 in 97% of patients and 50 % of them presented current alcohol intoxication. 69% (n=208) received 3 cycles of TPF, and 91% (n=268) underwent R associated or not with P (n=167) or C (n=51). 52% of patients (n=156) received the conform treatment (ie 3TPF + RP or RC). Grade 3-4 toxicities have been reported in 19% (n= 57), including 3% febrile neutropenia (n=9) and 7% kidney failure (n=22). Grade 3-4 toxicity, during TPF induction, led systematically to permanently discontinuation of the chemotherapy. Overall response rate after TPF induction was of 88% with 23% of complete response. After a median follow-up of 21 months, median progression-free survival and cause-specific survival (SS) were not reached. Median overall survival (OS) was 49 months (95% CI 31.2-66.8). SS and OS were significantly improved (p<0.0001) in patients who received the conform treatment. In multivariate analysis the probability of death related to cancer or to toxicities induced by treatment was increased for hemoglobin level ≤ 12.6g/dl or GGT level ≥ 77U/I [HR = 3.45 (95% CI: 1.50-7.93) p=0.0029]. Conclusions: We propose to use a biological index based on baseline hemoglobin and GGT levels to select patient for induction therapy in SCCHN. This simple index, predictive of treatment conformity and specific survival, needs further prospectives investigations.
Induction chemotherapy with weekly cetuximab, carboplatin, and paclitaxel in the treatment of locally advanced head and neck cancer: The University of Pennsylvania experience.
Authors: Bauman Jessica R , Langer Corey J. , Quon Harry , Algazy Kenneth M. , Desai Arati Suvas , Mutale Faith , Lin Alexander , Weiss Jared
Published: March 2020

e16062

Background: Although Tax 324 demonstrated superior survival for induction docetaxel, cisplatin, and 5-fluorouracil (TPF) compared to PF in the management of locally advanced head and neck cancer, TPF is associated with serious toxicities and logistical challenges leading many institutions to seek alternative regimens. One promising regimen, piloted by Kies and Wanebo, combines weekly cetuximab with carboplatin and paclitaxel, which the University of Pennsylvania adopted in 2008. Methods: We retrospectively evaluated all LA-SCCHN patients treated with this regimen from May 2008 to December 2011, during which time it was the only one used. Most commonly, cetuximab was dosed at 400mg/m2 IV alone week one, followed by 250mg/m2 weekly in combination with weekly carboplatin AUC 2 and paclitaxel 90 mg/m2 over eight weeks. Our primary endpoint was feasibility. Results: Thirty patients were included. Median follow-up was 13.7 months (range, 5.0-38.7). Median age was 58.3 (range, 37.4-83.6). All but one had Stage IV SCCHN. 77% had oropharyngeal carcinoma. 70% were smokers. p16 staining as a surrogate for HPV positivity was available on 13 patients, of whom 10 were positive. For induction, high tolerability was observed based on 90% of patients receiving all planned cycles or missing only one cycle. Grade 3-4 toxicities included rash (7%), neutropenia (7%), and infusion reaction (3%). Only 10% were hospitalized at some point during induction therapy. All patients subsequently received definitive chemoradiotherapy (29) or surgery (1). All completed their full treatment course. At the time of post-treatment imaging, 19 (63%) had a complete response and 11 (37%) had a partial response. Of p16 positive patients, 8/10 (80%) had a CR. Of p16 negative patients, 1/3 (33%) had a CR. At the time of last follow-up, 30% of patients had recurrent disease. Median overall survival and progression free survival have not yet been reached; Kaplan-Meir curves will be shown. Conclusions: Induction chemotherapy with weekly, outpatient, cetuximab, carboplatin, and paclitaxel is feasible and well tolerated in LA-SCCHN. Preliminary efficacy results are promising.
Interventions to reduce racial and ethnic disparities in colorectal cancer care: A systematic review.
Authors: Ward James Edward , Naylor Keith , Polite Blase N.
Published: March 2020

e16509

Background: Disparities in colorectal cancer (CRC) outcomes among underrepresented racial and ethnic minority patients continue to widen. We performed, and present here, the results of a systematic review of the literature evaluating interventions to reduce racial and ethnic disparities in CRC care. Methods: The MEDLINE, PsycINFO, CINAHL, and Cochrane databases were searched for articles that focused on interventions to reduce disparities in CRC screening, treatment, survivorship and end-of-life care from 1950 to 2010. Studies included were those that evaluated interventions in US populations that were composed of ≥50% racial/ethnic minorities (or that included a specific sub-analysis by race/ethnicity). Results: Following the electronic search, abstract and full text review, and reference reviews; a total of thirty-three studies were included in our final analysis. All of these were related to CRC screening; no studies evaluating the rest of the cancer care continuum were found. Nineteen studies (58%) were randomized controlled trials, nine (27%) were pre-test/post-test analyses, and five (15%) were cohort studies. Thirteen studies (39%) targeted African-American populations, eight (24%) targeted Hispanics, two (6%) targeted Asian populations, seven (21%) included a mixed population of ethnic minorities, and three (9%) were listed as “non-white” or included a subgroup analysis. The main results related to the magnitude of the effect of these patient-directed, patient navigator, and provider-directed interventions on CRC screening is outlined in the table below. Conclusions: Patient education involving personal contact, patient navigation services, and provider-directed education and reminder systems can modestly improve adherence to CRC screening among minority patients. Further studies targeting the rest of the colon cancer care continuum are needed. [Table: see text]
The impact of insurance health care on radiotherapy (RT) patterns of care in non-small cell lung cancer (NSCLC).
Authors: Lally Brian E. , Arsenault Daniel M.
Published: March 2020

e16518

Background: Access to surgical care and imaging modalities in NSCLC patients are well documented to vary by race/ethnicity. Little information regarding disparities of RT technology usage in NSCLC patients exists. We studied the impact of insurance type on the utilization of radiation technology to investigate this further. Methods: We used the Florida Cancer Data System (FCDS) to create a cohort of adult, pathology-confirmed NSCLC patients who received external beam radiotherapy. Cases of NSCLC were included if they had complete information on date of diagnosis, type of insurance, and race (white or black; others were excluded). Only patients whose radiation therapy codes were either conformal radiotherapy (CRT) or intensity modulated radiotherapy (IMRT) were included. The chi square test was used to statistically assess the differences between the groups examined. Results: Our cohort included 2759 (92.7%) white patients and 218 (7.3%) black patients. 3.4% of white patients were uninsured vs 7.8% of black patients (p=0.007). Moreover, there was a statistically significant difference in the utilization of IMRT vs. CRT with respect to race (p=0.003). Specifically, 59.8% of white patients receive IMRT vs 49.5% of black patients. Subset analysis of white patients did not reveal a significant difference in RT technology utilization with respect to insurance status: 53.1% of uninsured white and 61.6% of insured white patients received IMRT (p=ns). However, a similar subset analysis of black patients revealed that only 17.6% of uninsured black patients and 48.5% of insured black patients received IMRT (p=0.045). Conclusions: The utilization of RT technology varied significant with respect to insurance status in the black population. An uninsured black patient is less likely to receive IMRT when compared to an uninsured white patient. Longer follow-up and clinical correlation is needed to determine the clinical significance of this finding, but work is needed rectify any potential disparities with respect to radiation therapy.
Characterization of health care resource utilization and costs in women with metastatic breast cancer in Medicaid.
Authors: Wang Zhixiao , Li Xuan , Faria Claudio
Published: March 2020

e16521

Background: The costs of treating patients with metastatic breast cancer (mBC) have been examined in several studies, but there is very limited information regarding healthcare resource utilization (HCRU) and costs of mBC among Medicaid beneficiaries. The objective of this study was to characterize HCRU and costs in Medicaid among women with mBC. Methods: Women with mBC who were younger than 65 were identified using Thomson Reuters’ Medicaid claims data from 12-13 states (2005-2009). Overall HCRU and medical costs were estimated in those patients and compared to breast cancer (BC) patients without metastasis identified in the same population. Index date is the date of BC (or mBC) diagnosis and patients were followed to the date of disenrollment or the end of the study period, whichever occurred first. Mean (95% CI) cumulative healthcare costs were estimated using Kaplan-Meier Sample Average method. Results: 4,745 patients were included in the analysis. Among them, 3,767 were BC patients without metastasis and 978 with mBC. During an average of 14 months of follow up time, mBC patients on average incurred 1.56 hospital admissions, 9.01 inpatient days, and 1.97 emergency room (ER) visits, 25.54 physician office visits, 21.43 hospital outpatient visits, and 40.96 prescriptions. The total medical cost averaged at $63,068 (95% CI: $59,504, $66,624) per mBC patient, of which 33.0% were hospitalization costs, followed by hospital outpatient cost (27.4%) and physician office visit cost (14.8%). The average follow up time for BC patients was 18 months, during which BC patients on average incurred 0.69 hospital admissions, 3.79 inpatient days, 1.96 ER visits, 19.96 physician office visits, 12.27 hospital outpatient visits, and 40.89 prescriptions, and the total cost averaged at $29,776 (95% CI: $28,795, $30,762). Major cost drivers by type of service are similar to mBC. Conclusions: Overall HCRU and costs are substantially higher in mBC patients compared to BC patients of earlier stages in the Medicaid population, and the major cost drivers are similar in mBC and BC. Continuous Medicaid coverage is essential for BC/mBC patients in financial disadvantage to have access to quality medical care.