bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic factors in ovarian cancer patients with brain metastases: Results of a German multicenter study
Authors: El Khalfaoui K. , Oskay-Ozcelik G. , Richter R. , Pietzner K. , Harter P. , Münstedt K. , Mahner S. , Hasenburg A. , Wimberger P. , Sehouli J.
Published: August 2020

e16527

Background: Ovarian cancer is one of the leading causes of mortality in women with gynaecological malignancies. Brain metastases from ovarian cancer are rare. Up to this point there are only few data about prognostic factors for this patient collective. Methods: Within a period between 1981 and 2008 we analyzed 4,277 women with histologically confirmed ovarian cancer from six different German hospitals. Overall 72 women with brain metastases and two cases of meningosis carcinomatosa were identified, these resulting in an incidence of 1.73%. Results: The median age at the diagnosis of central nervous system (CNS) metastases was 58 years (range, 33–83). The median interval between the time of the first diagnosis of ovarian cancer and the occurrence of CNS metastases was 28.8 months (range, 3.6 -133.1). The median overall survival time after diagnosis of CNS metastases was 6.1 months (range, 0.2 -41.5). Multiple brain metastases were observed in 58 women (78.4%). Headache (36.5%), vomiting and nausea (17.1%) were the most frequent clinical symptoms. According the multivariate analysis following clinical parameter reached statistical significance: multiple lesions (hazard ratio (HR): 4.1, 95% confidence intervaI (CI): 1.9 to 8.9), grading I und II (HR: 2.8, 95% CI: 1.6 to 5.0) were associated with a negative impact on overall survival. Platinum sensitivity (HR: 0.28, 95% CI: 0.15 to 0.52) and the application of multimodal therapy strategies (surgery, radiotherapy and chemotherapy) (HR: 0.51, 95% CI: 0.28 to 0.92) and the good performance (HR: 0.52; 95% CI: 0.25 to 1.08) showed a positive impact on overall survival. Tumour histology, ascites and age at the CNS diagnosis were not significant for the survival. Conclusions: Next to the presence of multiple brain lesions and the performance status, the sensitivity to platinum based chemotherapy has an important positive impact on overall survival. This should be considered in the conduction of multimodal therapy strategies for brain metastases from ovarian cancer.

No significant financial relationships to disclose.
A pharmacogenetic UGT1A1 dose-escalation study for recurrent and refractory gynecologic cancer patients treated with combination therapy of irinotecan and cisplatin
Authors: Takano M. , Kato M. , Yoshikawa T. , Hirata J. , Takahashi M. , Yokota H. , Kino N. , Goto T. , Konno R. , Fujiwara H.
Published: August 2020

e16536

Background: In addition to polymorphisms of UGT1A1*28, UGT1A1*6 has been recognized as a risk factor for severe irinotecal-related toxicities. We have conducted an UGT1A1 genotype-based dose-escalation study for recurrent and refractory gynecologic cancer patients (pts) treated with combination with irinotecan and cisplatin (CPT-P). Methods: Pts eligible for this study had histologically confirmed uterine cancer or ovarian cancer, who received CPT-P; a course of therapy consisting of 40–80 mg/m2 of irinotecan on days 1, 8, and 15 and 60 mg/m2 of cisplatin on day 1, q4weeks. Polymorphisms of UGT1A1*28 and *6 were analyzed and the pts were categorized into three groups (wild-type, hetoro-type, and homo-type). Pharmacokinetics of CPT-11, SN-38, SN-38 glucuronide (SN-38G), and platinums were analyzed according to the UGT1A1 genotyping. Results: During August 2008 and December 2008, 17 pts were enrolled in this study; 12 ovarian cancers and 5 uterine cancers. Genotypes of UGT1A1 were wild in 9 pts (53%), *28 in 4 pts (24%), *6 in 3 pts (18%), *6/*6 in 1 pt (6%). At the starting doses of irinotecan (60 mg/m2 for wild-type and 40 mg/m2 for hetero-/homo-type), dose limiting toxicities were observed in two of six wild-type cases and one of six hetero-type cases. Pharmacokinetic analyses revealed hetero-type cases were associated with lower area under time-concentartion curve (AUC) SN-38G to SN-38 (AUCSN-38G/AUCSN-38) compared with wild-type cases (p = 0.02), however, there was no significant difference of AUCSN-38at the starting dose. Additionally, AUC of platinum was slightly higher in hetero-type cases in comparison with wild-type cases (p = 0.04). Pharmacokinetics of the drugs were similar between *28 and *6 cases. Conclusions: The present study indicated clinical significance of UGT1A1 genotyping upon pharmcokinetics of not only SN-38G/SN-38 but also platinum. In addition to UGT1A1*28, UGT1A1*6 was a key candidate to influence the pharmacokinetics of CPT-P regimen in gynecologic cancer patients.

No significant financial relationships to disclose.
Clinical outcome in patients with endometrial papillary serous and endometrioid carcinomas as related to WT-1, Pax-2, and p16 immunohistochemical expression profiles
Authors: Rollins-Raval M. , Byler Dann R. , Edwards R. P. , Chivukula M.
Published: August 2020

e16547

Background: Endometrial papillary serous carcinoma (EPS) can be difficult to differentiate histologically from high grade endometrial endometrioid carcinoma (EE). Both of these tumors often present with solid growth pattern with few papillary features. Recurrences have been found to be more frequent in EPS than high grade EE. These differences were found despite the same preoperative and postoperative radiotherapy and chemotherapy, indicating more aggressive tumor biology. To date, there are no well defined immunophenotypic or molecular methods to differentiate these two tumors or their clinical behavior. Methods: Eleven cases of EE and twenty-three cases of EPS were retrieved from our departmental archives and stained using Pax-2, WT-1 and p16 antibodies. For all three antibodies, a strong nuclear staining is considered positive. The intensity and proportion of cells positive are noted. Seven cases from each group were further examined for their staging and clinical outcome in terms of recurrence, metastasis and treatment. Results: WT-1 is negative in 100% of EE cases. p16 is positive in 95% of EPS cases, and only 55% of EE cases. In addition, out of the seven EPS patients whose clinical information was obtained, the three EPS patients who had strong Pax-2 staining are still alive more than two years status post surgical intervention, while four other EPS patients are deceased. The three patients with the strongly staining PAX-2 EPS tumors all had varying tumor characteristics, recurrence and adjuvant therapies. This finding is now being evaluated in the additional cases. Conclusions: WT-1, Pax-2 and p16 are useful to differentiate high grade EE and EPS cases. Strong Pax-2 staining in three cases of EPS with better outcome is an interesting finding that deserves further investigation.

No significant financial relationships to disclose.
Experience with endometrial carcinoma (EC): A population-based study in Tarragona Province (Spain)
Authors: Arenas Prat M. , Rovirosa A. , Sabater S. , Ameijide A. , Henríquez I. , Servitja S. , Cabezas I. , Mur E. , Gumà J.
Published: August 2020

e16550

Background: To evaluate outcome, failure patterns, prognostic factors and radiotherapy (RT) toxicity after postoperative RT for EC in Tarragona Province (Spain). Methods: A retrospective population-based review on 232 patients (pts) between 1997 and 2000 from different gynaecological Dpt. and in a single oncologist institution with RT Units. Multivariate analysis of disease-free survival (DFS), overall survival (OS), adjuvant RT, RT toxicity (RTOG), prognostic factors for survival, and the distance in Km to the RT Units. Results: Mean age: 64 years (35–88). Distance to RT Units >70 Km in 15% pts. Median follow-up: 70 months (2–132). FIGO Stage (S): 8.2% IA; 36.2% IB; 19% IC; 7.8% IIA; 6.5% IIB; 7.3% IIIA; 1.3% IIIB; 3.4% IIIC; 2.6% IVA; 2.2 IVB. Pathology: endometrioid 74.5%, papillary 3.9%, serous 3.4%, clear-cell 2.2%, squamous cell 3%, adenosquamous 1.3%, mixed 3.9%. Grade (G): 35.7% G1, 45.3% G2, 19% G3; miometrial invasion: 44.1% >50%, 46% <50%, 9.9% not invasion. Treatment: 1) Surgery in 93.5%, 49.6% lymph nodes dissection. 2) RT in 73.5%: 47% external beam radiotherapy (EBI) and brachytherapy (BT), 9.4% BT alone, 17.1% EBI alone. 3) Chemotherapy in 11.1% and hormonal treatment in 6.9%. 3). Grade 3 and 4 toxicity: 12 (9%) pts, 6 early and 6 late. Relapses: 26/232 (11.6%), S-I: 11/26 (42%), S-II: 1/26 (3.8%), S-III: 5/26 (19.2%), S-IV: 3/26 (11.5%). Metastasis: 28/232 (12.5%). Survivals at 5 years: 1) OS in all stages was 78.8% and 83%, 89.6%, and 76% for SI, SII, and SIII, respectively. 2) DFS was 76.5% for all pts and 82.3%, 86.22%, and 68.24% for SI, SII, and SIII, respectively. Multivariate analysis: significant prognostic factors for poor outcome were age (p < 0.01), lymph nodes dissection (p < 0.001), pathologic subtype (p < 0.001), grade of differentiation (p < 0.001), and deep myometrial invasion (p < 0.005). Conclusions: Survivals, RT toxicity and relapse sites were similar to the other reported series. Predictors of poor outcome were age, lymph nodes dissection, pathology subtype, grade of differentiation, and deep myometrial invasion. Patients of Tarragona Province are in need of a better accessibility to the radiation units.

No significant financial relationships to disclose.
Phase II trial of imatinib mesylate (I) in combination with docetaxel (D) in the treatment of patients (pts) with recurrent or persistent epithelial ovarian carcinoma (EOC)
Authors: Usha L. , Larson M. L. , Kazmi N. , O'Brien T. , Winkelman L. A. , Rotmensch J.
Published: August 2020

e16552

Background: D has a known single-agent activity in advanced EOC with the response rate of at least 10%. I is a multi-targeted tyrosine kinase inhibitor shown in preclinical studies to decrease interstitial pressure in the tumor and facilitate influx of chemotherapeutic agents into the tumor. Methods: A single-institution trial was conducted in pts with advanced EOC in 2005–2007. The primary endpoint of the study was to determine a tumor response to the study combination. Pts were required to have received 1 or 2 prior chemotherapeutic regimens including a platinum compound and have performance status 0–2. Pts were to receive D 60 mg/m2 IV every 3 weeks and I 400 mg/day by mouth continuously. Planned target accrual for the first stage of the study was 15 pts with the preset minimum of 3 responses to proceed to the second stage. Tumor response was evaluated by RECIST criteria after every 3 cycles of D. Treatment was continued until disease progression or unacceptable toxicity. Results: Study was terminated early due to lack of response and significant toxicities. A total of 10 pts were enrolled. The age range of the pts was 55–79 with the mean age = 64. Five pts were evaluable for response and in all of them, cancer progression was observed after 3 cycles of combination therapy (0 responses). Five pts were taken off the study after 1 cycle of treatment either due to serious adverse events (SAEs) or disease progression. Among grade 3 and 4 SAE's observed in the study were 4 cases of hematological toxicity, 1 case of rash, 1 case of dizziness, and 1 case of deep venous thrombosis. The median progression-free survival for pts on the study was 7.5 weeks. Conclusions: Although the sample size of this study was small, the combination of I and D at the above doses appears ineffective in the population of moderately-pretreated women with advanced EOC. The majority of grade 3 and 4 SAE's were due to myelosuppression likely caused by D rather than I.

No significant financial relationships to disclose.
The expression and clinical significance of clusterin and ki67 in cervical cancer
Authors: Shrestha E.
Published: August 2020

e16554

Background: To explore the expression pattern and clinical significance of the CLU and proliferation indices ki67 in cervical cancer. Methods: 59 cases treated at Cancer Center Sun Yat-sen University during 1989–2006 were enrolled in the study group. The relationship was analyzed for the expressions of CLU and Ki67 with clinical factors. Results: In this study positivity of CLU in cervical SCC, 10% (3/31) cases weak positive, adenocarcinoma 21% (4/19) weak positive in small cell carcinoma 11% (1/9) moderate positive. Control groups, CLU weak positive expression, 21% (3/14) CIN 2–3 and 14% (2/13) normal squamous epithelium.CLU expression found 100% (31/31) normal endocervical glands.The Ki67 in SCC 13% (4/31) cases weak positive and 5% (1/19) adenocarcinoma. All cases small cell carcinoma revealed negative. No significant difference of the CLU expression rate between normal cervical epithelium, CIN II-III and SCC (p = 0.561). No significant difference of CLU expression rate between normal endocervical gland and adenocarcinoma (p = 0.119) as well. In Ki67, there was no significant difference of Ki67 rates between CIN 2–3 and normal squamous epithelium (p = 0.585). No significant difference of Ki67 expression rates between adenocarcinoma and normal squamous epithelium (p = 0.341). The expression of CLU and Ki67 had no correlation with FIGO stage, SCC antigen level, grade of differentiation, deep stromal invasion, and lymph node metastasis. Finally, the expression of CLU and Ki67 was not related to the 5-years DFS rates, and CLU expression was not correlated with Ki67 expression (rs = 0.500, p = 0.391). Conclusions: CLU and Ki67 was in lower rates in cervical cancer, and was not associated with any clinicopathological features. It is suggested that CLU and Ki67 have no distinct role in carcinogenesis. The further larger studies are needed to verify the results of this study.

No significant financial relationships to disclose.
Treatment of advanced chemo-refractory epithelial ovarian cancer with aromatase inhibitor
Authors: Shaharyar A. , Shami N. , Zia N. , Hafeez M. , Rasheed H. , Saleem T. , Zulfiqar S. , Masood A. I.
Published: August 2020

e16561

Background: In advanced epithelial ovarian cancer non-steroidal antiestrogens yields clinical responses in a significant number of patients. This raises the possibility of therapeutic effectiveness of aromatase inhibitors in epithelial ovarian cancer in post menopausal women. Therefore this study was carried out to document the effectiveness of an aromatase inhibitor, in advanced epithelial ovarian cancer patients with unknown hormone receptor status. Methods: From January 2006 to April 2007, a total of 38 patients were enrolled. Patients with histopathologically confirmed advanced epithelial ovarian cancer were included. Other eligibility requirements were: postmenopausal women, failure of third-line chemotherapy, age between 50–70 years, bidimensionally measurable disease, and CA-125 of more than 100 u/mL. An adequate hematologic, hepatic, and renal profile, and ECOG performance of 0–2 was required. Tablet letrozole 2.5 mg orally once daily was given for 03 months. CA-125 and Miller criteria were used for response evaluation. Results: No patient showed the evidence of complete or partial clinical response. Four patients had stable disease for 8 weeks. All patients showed progressive disease on week 12. Conclusions: In this small series no evidence of effectiveness of aromatase inhibitor letrozole in chemo refractory epithelial ovarian cancer is documented in patients with unknown hormone receptor status. It is, therefore, recommended that further study should only be carried out in the selected patient population with documented positive ER/PR hormone receptors.

No significant financial relationships to disclose.
Capping the dose of paclitaxel in endometrial cancer patients: Does this affect clinical outcome?
Authors: Hanna R. K. , Shafer A. , Van Le L.
Published: August 2020

e16563

Background: Various protocols recommend capping chemotherapy dosing of paclitaxel at 2m2 while other protocols dose paclitaxel according to actual body weight (ABW). In endometrial cancer where a significant portion of patients are obese this dosing difference may affect clinical outcome. We performed a retrospective review of patients with endometrial cancer who received paclitaxel and carboplatin after surgical staging. We compared patients who received paclitaxel dosed according to ABW with patients whose dose was capped at 2m2 to determine if differences in dosing affected progression free survival (PFS). Methods: Patients with endometrial cancer undergoing adjuvant treatment with paclitaxel and carboplatin from January 2000 to January 2008 were identified. Patient age, endometrial histology, stage, BSA, and paclitaxel treatment dose were collected and progression free survival was determined. Differences in outcome were compared and evaluated using student's t test. Results: 109 women were identified of whom 70 were treated according to their ABW (<2m2) and 39 obese patients received paclitaxel dose capped at 2m2. 95% of all the patients received the complete course of chemotherapy. PFS for both groups were 21.4±2.2 and 23.2±2.2 months with no significant difference in PFS (p = 0.62). When evaluating patients with endometrioid histology alone, no difference between patients receiving dosages according to ABW compared to those whose dosages were capped at 2m2 (25 patients vs. 19 patients, PFS 19.3±3.7 and 27.0±3.7 respectively, p = 0.16). However for patients with serous histology, PFS was significantly greater in those patients treated per their ABW when compared to patients capped at 2m2 (45 patients vs. 20 patients, PFS 30.2±3.2 and 19.6±3.5 months respectively, p = 0.05). Conclusions: There was no difference in PFS for patients with endometrioid cancer who were treated with ABW vs. capped doses of paclitaxel. However patients with serous histology experienced longer PFS when receiving paclitaxel dosed per ABW as compared to patients whose dose was capped at 2m2. This difference may reflect increased sensitivity of serous cancers to chemotherapy or other unknown biologic variables. Capping paclitaxel dosing in patients with serous endometrial cancers may affect their PFS.

No significant financial relationships to disclose.
Gestational trophoblastic disease in Nepalese women managed in B. P. Koirala Memorial Cancer Hospital
Authors: Pariyar J.
Published: August 2020

e16570

Background: Gestational trophoblastic disease (GTD) is potentially curable disease. Its incidence varies in different countries with high incidence reported in Japan (2/1000 pregnancies) and Mexico (2.5/1000 pregnancies). No studies have been reported regarding epidemiology, management and outcome of GTD in Nepal. Methods: The study was a descriptive case series. Case records of GTD patients attending B.P. Koirala Memorial Cancer Hospital, Nepal from 2001 to 2007 were analyzed. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and follow-up. Results: A total of 45 cases of gestational trophoblastic disease (GTD) were received from 26 districts of Nepal. The age of the patients ranged from 16 to 50 years with a mean age of 29.1 years (SD 9.4 years). Out of 45 cases 19 (43%) were of Tibeto-Burmese ethnic group and 15 (33%) belonged to Indo-Aryan ethnic group. There were 17 cases (37.8%) of hydatidiform mole, 6 were invasive mole (13.35%), 4 of persistent gestational trophoblastic tumour (8.8%) and 22 patients (48.8%) of choriocarcinoma. In 7 cases (15.5%) molar pregnancy had occurred in the first conception, another 7 cases (15.5%) had previous molar pregnancy and in 16 (35.5%) cases GTD had occurred following abortion. The most common presenting symptom was vaginal bleeding and 26 (57.8%) patients had anaemia. Theca Leuteal cyst was present in 11 (24.5%), 17 (37.8%) cases had lung metastasis, 4 (8.9%) had brain metastasis and another 4 (8.9%) had disseminated disease detecteted radiologically. Among the 45 cases 6 (13.3%) were treated with suction evacuation only; 9 (20%) underwent hysterectomy for uterine perforation, excessive hemorrhage and invasive mole. 28 (62.2%) cases underwent adjuvant chemotherapy among which 12 (26.6%) received single agent chemotherapy and 15 (33.3%) received EMA-CO regimen. Brain irradiation was required in a case with brain metastasis. Five (11.1%) cases with disseminated disease and high WHO risk score left the hospital against medical advice. There were 3 (6.7%) mortalities. 37 (82.1%) cases are in remission and follow-up. Conclusions: Early diagnosis of disease and proper management strongly influences the outcome of GTD. Even in disseminated state GTD can be cured.

No significant financial relationships to disclose.
Surgical treatment for early cervical cancer: Experience at a cancer hospital in Nepal
Authors: Dangal G.
Published: August 2020

e16575

Background: The purpose of this study was to find out the clinocopathologic characteristics, post-operative findings and complications of patients with early (up to stage IIA) cervical carcinoma who underwent radical hysterectomy. This study concentrates on the evaluation of our early experience in radical hysterectomy for cervical cancer in Nepal. Methods: This was a retrospective analysis of 48 patients who had radical hysterectomy with bilateral pelvic lymphadenectomy for early cervical cancer at the BP Koirala Memorial Cancer Hospital (BPKMCH) from September 2002 through September 2005. Characteristics such as chief complaint, disease staging and duration, intraoperative and postoperative complications, histopathological findings, need for blood transfusion, and duration of hospital stay were considered for analysis. Results: Patients’ age ranged from 28–67 years. Age group of 40–49 had highest number of patients (58.3%). Majority (62.5%) were premenopausal women who presented with abnormal vaginal bleeding (73%) as the chief complaint. More than half of them (56%) had FIGO stage IIA disease. Thirty-three percent had intraoperative and postoperative complications such as urinary problems, wound infection and vessel injury/ureteric injury. All needed blood transfusion, 42% needing four pints. The average duration of hospital stay was 11 days. Forty-four had squamous cell carcinoma and four had adenocarcinoma. Pelvic lymph node metastasis was found in 10 patients. Resected margins were adequate in 42 patients. Majority (62.5%) of the women were premenopausal and 56% of them had stage IIA disease. Conclusions: Although the primary treatment of early-stage cervical carcinoma involves either surgery or radiation therapy with or without chemotherapy, surgery (radical hysterectomy) was used for lower-stage disease and smaller lesions in fit and young patients in our resource-poor set-up. The complication rate seems to be higher in Nepal; however, it will decrease as more experience is gained.

No significant financial relationships to disclose.
Acute toxicity to the skin and mucosa of radiotherapy alone versus radiotherapy in combination with cetuximab or chemotherapy in patients with head and neck cancer
Authors: Garcia-Huttenlocher H. I. , Timke C. , Jensen A. D. , Huber P. E. , Debus J. , Muenter M. W.
Published: August 2020

e17007

Background: To evaluate acute toxicity of the skin and mucosa in patients with head and neck cancer who received Radiotherapy alone (RT) or in combination with cetuximab (IRT) or chemotherapy (CRT). Methods: We retrospectively analyzed 204 patients with head and neck cancer, treated between 2006 and 2008. RT was combined with cetuximab (n = 57), or with platinum-based chemotherapy (n = 99), 48 patients received RT alone. We included 149 male and 55 female patients with a median age of 62 years (range 22–92). Median radiation dose was 66 Gy (range 26.4–71.6Gy). 126 patients received intensity modulated radiotherapy (IMRT), 78 patients had conventional RT. Toxicity was assessed according to CTCAE Version 3.0. Results: Median follow-up was 9 months (range 1–34). Acute grade 3 toxicity of the skin was observed in 26% of IRT, 0% of RT, and 7% of CRT patients. Typical appearance of grade 3 skin toxicity in IRT was a massive confluent epitheliolysis of the RT field. Grade 3 mucositis appeared in 21% of IRT-, 12.5% of RT-, and 16% of CRT-patients. Rates of skin toxicity grade 3 were 8% in patients with IMRT and 15% in patients with conventional RT. Grade 3 mucositis was seen in 22% of the IMRT-patients and 8% of the patients with conventional RT. Cetuximab did not lead to a higher rate of RT interruptions as compared to RT and CRT. Early intervention and supportive care in case of high grade toxicity was performed for all patients. 8 weeks after RT all patients showed recovery from toxicity. Conclusions: Higher toxicity to the skin and to the mucosa occurred in the IRT group, and seems to be a specific side effect in the treatment of head and neck cancer patients with concomitant cetuximab and RT. But severity of toxicity may also be influenced by other factors such as RT technique. IRT patients need close observation and early intervention in case of therapy induced toxicity in order to prevent RT interruption, which might limit the advantage of cetuximab. Longer follow-up is needed to evaluate outcome and late toxicity of the different treatment groups.

[Table: see text]
Impact of interobserver variability in delineating clinical target volumes (CTV) for head and neck intensity modulated radiation therapy (IMRT): Potential for a geographical miss
Authors: Chilukuri S. , Surana S. , Mohanty P. P. , Kuppuswamy R.
Published: August 2020

e17013

Background: Despite modern day imaging techniques and guidelines for delineation of the clinical target volume, there remains significant inter-observer variability in delineating the CTV. With the use of IMRT, the target volume receives a significant tumoricidal dose while the regions just outside the target receive unpredictable doses. In this report, the dose to the region just outside the planning target volume (PTV) (defined as volume of uncertainty [VOU]), presumed to represent the regions subject to maximum inter-observer variability, was studied. Methods: The IMRT plans of 12 patients with head and neck cancer were used to determine the dose just outside the high-risk CTV by growing volumes around CTV with 3 mm, 5 mm, and 7 mm margins. These volumes were edited at regions close to skin/air and bone. PTVs were subsequently grown using the same margins as used in the original plans. With the Boolean operations, each of these volumes was subtracted from the existing PTV to generate the volumes of uncertainty (VOU) in 3 dimensions. The dose to these VOUs was analyzed. D95, D90 and median dose which are the doses received by 95%, 90%, and 50% of the target volume respectively were studied. Results: The median prescribed dose was 68 Gy (60 Gy-72 Gy). The median percentage D95 for 3mm, 5mm and 7mm VOU was 82.5% ± 4.95, 77.25% ± 5.53, and 69% ± 6.93, respectively. The median percentage D90 for these VOU's was 87.7% ± 3.53, 83.2% ± 4.61, and 79% ± 4.5, respectively. The median dose to each of these VOU”s was 96% ± 1.6, 94.5% ± 1.95, and 92.5% ± 1.85 respectively. Conclusions: This study documents that the volumes of uncertainty surrounding the PTV, which could contain subclinical disease, in fact receive a significant amount of RT dose. Hence, despite a large amount of evidence for inter-observer variability in target delineation for head and neck cancer,the majority of locoregional recurrences are within the high dose region and not marginal failures.

No significant financial relationships to disclose.
Correlation of global expresssion of ERCC1 in head and neck squamous cell carcinoma with prognosis
Authors: Saada E. , Thariat J. , Ettore F. , Sudaka A. , Chamorey E. , Italiano A. , Poissonet G. , Bensadoun R. , Dassonville O. , Peyrade F.
Published: August 2020

e17016

Background: The overexpression of excision repair cross-complementation group 1 (ERCC1), element of the Nucleotid Excision Repair (NER) pathway has been associated with resistance to platinum-based chemotherapy. We studied the correlation of ERCC1 immunohistochemical expression with overall survival and cancer-specific survival in patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) treated with cisplatin-based chemotherapy. Methods: Using a monoclonal antibody against ERCC1 (clone 8F1, Neomarker), we analyzed its immunohistochemical expression in pretherapeutic samples of 142 HNSCC patients treated in our center from 2000 to 2006. Forty-three patients were treated with surgery followed by adjuvant radiochemotherapy, 86 with concomitant radiochemotherapy with or without neoadjuvant chemotherapy and 13 with cisplatin-based chemotherapy for metastatic disease. Two independent observers blinded to clinical data evaluated ERCC1 expression using the H-score protocol (ranging from 0 to 3). Survival rates were estimated using the Kaplan-Meier method. Survival univariate analysis was performed using log-Rank test. Results: ERCC1was expressed intensively and diffusely in the nuclei 89% of the tumor samples had an H-score at least equal to 2. Treatment type and metastatic status were predictive of overall survival (respectively, p = 0.003 and p = 0.005). Higher expression of ERCC1 tended to be correlated with longer overall survival (p = 0.08). Conclusions: Our observations are at variance with recently published data about the predictive role of ERCC1 (Handra Luca CCR 2008). Overexpression of ERCC1 has also been associated with better outcome of operated NSCLC. Such differences may be due to inherent biological differences between study populations and certainly attributable to different roles of ERCC1 through oncogenesis.These controversial correlative results among studies and the intense and diffuse patterns of ERCC1 expression might also indicate a central role of ERCC1 in HNSCC oncogenesis and then provide a potential target. Further investigations about the role and predictive value of ERCC1 protein in anticancer treatments including cisplatin are warranted.

No significant financial relationships to disclose.
Concurrent chemoradiotherapy with weekly docetaxel and cisplatin for locally advanced head and neck cancer: Phase I study
Authors: Kim H. S. , Park K. , Ahn M. J. , Park Y. , Lee S. , Baek C. , Son Y. , Jeong H. , Ahn Y. , Park B.
Published: August 2020

e17026

Background: This phase I study was performed to determine maximum tolerated dose of docetaxel when administered concomitantly with radiotherapy and cisplatin in patients with locally advanced head and neck cancer. Methods: Fifteen patients were treated at varying levels of docetaxel (level 1: 0 mg/m2, level 2: 10 mg/m2, level 3: 15 mg/m2, and level 4: 20 mg/m2, once per week for a total 6 weeks) with a fixed dose of 20 mg/m2 cisplatin weekly on an outpatient basis. Radiotherapy was delivered as a standard regimen (1.8–2.0 Gy/day, 5 fraction/week) to a total dose of 66–72 Gy. Results: One out of six patients presented with dose-limiting toxicity at the 10 mg/m2/week dose of docetaxel (grade 4 febrile neutropenia which results in treatment-related death). No DLTs was noticed at the 15 mg/m2, and 20 mg/m2 dose level. Thus, the weekly docetaxel dose of 20 mg/m2 was considered as the maximum tolerated dose. Radiotherapy was completed in all patients except one, and more than 95% of the scheduled cisplatin and docetaxel were given in 93% of patients. Acute grade 3–4 toxicities were dominated by anorexia (26.7%), xerostomia (13.3%), and febrile neutropenia (6.6%). Eight (57.1%) and six (42.9%) patients had complete response and partial response. The 2-year actuarial overall survival rate and local control rate were 93.3%, and 87.5%, respectively. With a median 17.5 months (1.25–23.6) of follow-up, 13 out of 14 patients are still alive without evidence of diseases, and only one is alive with evidence of diseases. Conclusions: We determined the MTD of docetaxel to be 20 mg/m2 administered once weekly concurrently with combined with conventionally fractionated RT and weekly 10 mg/m2 CDDP. This chemoradiotherapeutic regimen serves as a promising treatment modality, in which level 3 is the recommended dose for a phase II study.

No significant financial relationships to disclose.
Assessment of phosphatidylinositol-3 kinase (PI3K) as a prognostic marker in head and neck squamous cell carcinoma (HNSCC)
Authors: Pectasides E. , Founztilas G. , Sasaki C. , Burtness B. , Psyrri A.
Published: August 2020

e17028

Background: Deregulated signaling through phosphatidylinositol 3’-kinase (PI3K) pathway is common in several cancers, including HNSCC. In the present study we investigated the relationship between PI3K protein expression and outcome in patients with HNSCC. Methods: A tissue microarray composed of 122 specimens from primary HNSCC cases treated with either external beam radiotherapy (EBRT) or gross total surgical resection and EBRT was constructed. Protein expression levels for PI3K were analyzed using an immunofluorescence-based assay that provides an automated, quantitative analysis of expression within subcellular compartments (AQUA). Primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed by Kaplan-Meier method with log-rank test for assessing statistical significance. Results: Mean follow-up time for the cohort was 40 months. Ninety-seven of 122 cases had sufficient tissue for analysis and continuous AQUA scores were divided into quartiles. Survival analysis showed that patients in the top and bottom quartile had a significantly shorter OS (p = 0.015). In multivariable analysis, adjusting for well-characterized prognostic variables, PI3K expression retained its prognostic significance. Conclusions: Our study suggests that in situ quantitative measurement of PI3K stratifies HNSCC into four expression levels where both low and high levels are associated with a worse outcome. We speculate that transmission of growth factor receptor signals that promote tumor aggression in these low expressers may occur via PI3K/Akt independent mechanisms. It is possible that activation of such alternate pathways in some tumors results in the down-regulation of PI3K expression via a feedback mechanism, producing aggressive tumors bearing a PI3K-low phenotype.

No significant financial relationships to disclose.
Prognostic value of the expression of tumor necrosis factor-alpha (TNFa) and its receptors in head and neck cancer (HNC) patients: A pilot study
Authors: Clatot F. , Picquenot J. , Cornic M. , Hamidou H. , Tennevet I. , Choussy O. , François A. , Hong L. , Laberge-Le- Couteulx S. , Blot E.
Published: August 2020

e17029

Background: TNFa was initially described as an inductor of apoptosis in cancer cells. In vitro data showed that TNFa can also activate anti-apoptotic signaling in cancer cells. We analyzed the prognostic value of the expression of TNFa and its receptors TNFR1 and TNFR2 in HNC patients. Methods: Twenty-four patients treated for HNC were retrospectively analyzed for TNFa, TNFR1, and TNFR2 expression by real-time PCR (RT-PCR). Tissue samples were collected at the time of initial diagnosis. Total RNA was reverse-transcribed with TaqMan quantitative RT-PCR (Applied Biosystems). Results were recorded as average threshold cycle, and relative expression was determined using Normalized Expressions method. Expression of TNFa, TNFR1, and TNFR2 was related to survival after 3 years of follow-up. Results: In the 24 patients, expression of TNFa (mean value 7.8, median 2.4, range 0.02–62.3), TNFR1 (mean value 58, median 49, range 0.02–246.9) and TNFR2 (mean value 4.8, median 3.3, range 0.8–18.9) demonstrated a great variability between patients. After a 3-year follow-up, 14 patients were alive without evolution of cancer (group A) and 10 were dead because of cancer evolution (group D). In group D, median level of TNFa was 8.8 whereas it was 1.1 in group A (p = 0.02). Median level of TNFR1 was 71.8 in group D and 28.5 in group A (p = 0.01). In contrast, median level of TNFR2 was 3.3 for both groups. Patients with high level of TNFa or TNFR1 expression had a worse survival (p = 0.01 and p = 0.009, respectively). There was also a strong correlation between high expression of TNFa and of TNFR1 (p = 0.0007). Conclusions: In this small series, TNFa and TNFR1 expression seem to have significant prognostic value to predict survival of HNC patients. This result needs to be confirmed in larger series and compared with usual prognostic factor. It suggests that TNFa expression could have a dual effect in HNC and that TNFR1 expression may play a role in this process.

No significant financial relationships to disclose.
Analysis and utility of pretreatment and posttreatment total body iodine-131 scans in patients with thyroid carcinoma
Authors: Billan S. , Nasrallah H. , Abdah-Bortnyak R. , Kuten A.
Published: August 2020

e17031

Background: The purpose of this study was to evaluate the efficacy of post-I-131 treatment total body scans. Methods: The records of 108 consecutive patients with thyroid carcinoma treated by surgery and postoperative I-131 were reviewed. All patients underwent a postoperative diagnostic total body I-131 and post I-131 therapy scintigraphies .83% of patients were considered low risk according to AMES (age, metastasis, extracapsular extension, size) criteria. Results: The postoperative diagnostic total body I-131 scintigraphy revealed uptake in the neck in 95 out of 108 patients (88%). Three patients had lung and mediastinal uptake in known sites of metastatic disease. Additional foci of neck, mediastinal and lung uptake were revealed in the post-131 therapy total body scintigraphies in ten patients ( 9.3%). Variables found to correlate significantly with additional uptake on the post-I131 therapy total body scintigraphies were tumor size >4cm, lymph-node involvement and extracapsular extension. Conclusions: Post- I-131 therapy scans yielded additional information in 9.3% of the patients treated by postoperative I-131 for well differentiated thyroid carcinoma. The value of posttreatment scintigraphies is questionable in low risk patients.

No significant financial relationships to disclose.
Treatment-related toxicities in patients with squamous cell carcinoma of the head and neck (SCCHN)
Authors: Ulcickas Yood M. , Feng Wang P. , Hensley Alford S. , Oliveria S. , Wells K. , Phillips S. , Ali H. , O’Malley C. D.
Published: August 2020

e17041

Background: Although treatment effects and toxicities have been reported from randomized clinical trials of patients with squamous cell carcinoma of the head and neck (SCCHN), little information is available from real-world clinical practice where heterogeneous treatment patterns and patient populations may lead to different estimates than those observed in clinical trials. Methods: Using a population-based tumor registry at a large, Midwestern integrated health system, we identified all cases of stage III or IV SCCHN diagnosed 2000–2006. The incidence/severity of acute and late toxicities associated with SCCHN treatment was obtained from detailed medical record review of health system encounters, including physician notes. Grading of toxicities (using CTCAE3 criteria), distinction between acute and late toxicity, and analyses by treatment are ongoing. The incidence and severity of toxicities will be presented by treatment regimen, tumor location and tumor stage. We presented here an interim analysis. Results: Among the target population of 194 patients that will ultimately be included in this study, 137 medical record reviews have been completed to date. The percentages of patients with toxicities, including 95% confidence intervals are presented in the table , below. Conclusions: Toxicity in patients with advanced SCCHN is common. Data from clinical practice quantifying the incidence are lacking, these data from an observational real-world study provide important baseline information on the incidence of toxicities in patients with advanced SCCHN and also call for safer effective treatment for SCCHN.

[Table: see text]

[Table: see text]
Paclitaxel in relapsed squamous cell carcinoma of head and neck (SSCHN): Retrospective study of a single institution
Authors: Fayette J. , Montella A. , Bachelot T. , Pommier P. , Girodet D. , Racadot S. , Montbarbon X. , Favier B. , Zrounba P.
Published: August 2020

e17047

Background: For relapse or metastatic SCCHN the standard treatment is the combination of cisplatin and 5FU that showed higher response rate than methotrexate but similar overall survival. Cetuximab demonstrated in a phase III (N Engl J Med. 2008;359:1116) its efficacy and paclitaxel showed efficacy in a phase II study (Cancer. 1998;82:2270). The objective of this study was to evaluate paclitaxel (P) in our institution in various situations. Methods: We retrospectively reviewed 56 pts with relapse or metastatic SSCHN treated with P in a single institution in Lyon (France) between June 2002 and February 2008. P was administered in first line for locally advanced disease, in first line for relapsed or metastatic disease, or in second or more line. P was administered q1w or q3w, alone or in combination with carboplatin or cetuximab. Results: Median age was 59 years (36–84) at the beginning of paclitaxel. Localizations of primitive tumor: oral cavity (14%), oropharynx (30%), hypopharynx (39%) larynx (7%), rhinopharynx (4%), or other (6%). All patients received adequate initial treatment with surgery and/or radiotherapy, 47% had have neoadjuvant chemotherapy (71% with cddp-5fu, but 5 pts received P). Five patients received P as neoadjuvant treatment. Among 52 evaluable patients, 33 received P in first line of treatment after relapse, 12 in second line. Monotherapy was administered to 20 patients and 22 received P combined with carboplatin, and 1 with cetuximab. For all patients, objective response rate (OR) was 30.8% (95% CI 18.7–45.1%). In first line of relapse, OR was 39.4% (95% CI 22.9–57.9%) and 16.7% (95% CI 2.1–18.4%) in second line. In monotherapy OR was 30.0% (95% CI 11.9–54.3%) and 36.4% (95% CI 17.2–59.3%) in combination with carboplatin. The overall survival (OS) of all patients was 6.3 months (95% CI 3.9–7.9 m), and 7.7 m (95% CI 3.9–11 m) and 5.2 m (95% CI 2.8–7.9 m) in first and second line, respectively. There is no difference in OS between monotherapy and combination: 6.1 m (95% CI 3.9–7.9 m) and 5.3 m (95% CI 3.9–7.9 m), respectively. Conclusions: P did not improve overall survival but showed interesting response rate in relapsed patients who are often symptomatic. Recent studies suggest high potentialities in combination with EGFR inhibitors.

No significant financial relationships to disclose.
Pattern of head and neck cancers in a Nigerian tertiary health center: A 10-year review
Authors: Alabi S. , Rahman G. , Badmos K.
Published: August 2020

e17054

Background: Cancer is a rising health problem worldwide, Nigeria inclusive. A variety of different tumour types may arise at a host of sites within the head and neck region. This 10-year review is to assess the various sites of primary lesion, gender and age distribution and histopathological types, so as to update data with an earlier study done in our centre between 1997–2001. Methods: This 10 year review of patients with head and neck cancers was carried out at the University of Ilorin teaching, Ilorin, North central Nigeria between January 1997 and December 2006.The hospital is one of 2 teaching hospitals in the zone of 6 constituent states out of 36 states in Nigeria, with an average population of 5 to 6 million (2003 Nigerian census). Information extracted from the case notes of patients with histological results included: Age, sex, clinical features, site of tumour, and the histological types of tumour. The International classification of disease oncology (ICDO) ninth version was used to categorize the sites of the tumour. Results: A total of 138 cases of head and cancers were seen over the 10 year period with an average occurrence of 14 cases/year, male/ female ratio of 1.1 to 1.0, age range of 1.5 years to 85 years with a mean age of 45.23 years, the peak age incidence of fifth to sixth decades of life being 47.2%.The commonest histological type was carcinoma (78.3%), then lymphomas (12.3%), blastomas (5.1%), sarcomas (4.3%). The commonest site were the nose, paranasal sinuses and ears (23.9%), eye (15.2%), nasopharynx (13%), neck (13% -metastatic unknown primary 4.3%), thyroid (12.3%), larynx (10.2%), oral cavity and oropharynx (6.5%), salivary glands (3.6%), mandible (1.4%), and skin (0.74%). Conclusions: This result shows that head and neck cancers occur among Nigerians with no sex differentiation in their prime of life, the histological types are similar to the previous series, however the site seems to have changed with the nose and paranasal sinuses, eye, and nasopharynx being the commonest sites. The metastatic unknown primaries in the neck are much lower. The devastating effects on the individual, family and the community are enormous in a setting with late presentations at the hospital and a strong belief in traditional medicine. Emphasis on prevention of these cancers is stressed.

No significant financial relationships to disclose.
Actual proportion of patients (pts) receiving chemotherapy or cetuximab for head and neck squamous carcinoma (HNSC)
Authors: Grau J. J. , Caballero M. , Verger E. , Blanch J. L.
Published: August 2020

e17058

Background: With the new indications of chemotherapy or cetuximab in HNSC, the rate of pts receiving these therapies nowadays is unclear. Methods: This retrospective study identified all consecutive pts with HNSC from January 1, 2006, to December 31, 2007, presented in a multidisciplinary team to decide further treatment in a single institution. ASCO guidelines for larynx preservation were followed to select surgery or chemoradiotherapy (ChRt). We classified the intention-to-treat as palliative, adjuvant or induction therapy. In the last case, always with concomitant radiotherapy (Rt) or prior to concomitant ChRt. Cetuximab was indicated with Rt as induction therapy for pts with problems to receive platin-based chemotherapy. Results: : A total of 350 pts were identified, 320 were male (91%), and 30 female (9%), with mean age 60.4 (range 41–90). Primary tumor was located in glottis (41%), supraglottis (19%), hypopharynx (11%), oropharynx (20%), or mouth (9%). Staging was I (27%), II (22%), III (16%), or IV (35%). Surgery alone was performed in 136 pts (39%) and chemotherapy or cetuximab in 214 other pts (61%). The intention-to-treat was palliative in 69 (32%), adjuvant in 51 (24%), or induction 94(44%) of the pts respectively. Rt plus cetuximab was administered to 31/97 (33%) and Rt plus chemotherapy in 63/97 (67%) pts as induction therapy. During this 2-year period, some pts received both induction/adjuvant and palliative chemotherapy. Conclusions: Chemotherapy or cetuximab is indicated as part of treatment in more than a half of pts with HNSC. Induction therapy is the most frequent indication.

No significant financial relationships to disclose.