bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for nodal metastasis in women with grade 3 endometrial cancer.
Authors: Clark Leslie Horn , Ko Emily Meichun , Bae-Jump Victoria Lin , Gehrig Paola A.
Published: March 2020

e15511

Background: No studies have reported on the association of nodal metastases and lower uterine segment (LUS) in grade 3 endometrial cancer. Our study aimed to determine the frequency of nodal metastasis in these high-risk patients stratified by LUS involvement. Methods: A retrospective analysis was conducted on grade 3 endometrial cancer cases from 2005-2010. Statistical analyses were performed using summary frequencies and multivariate logistic regression analysis, with two-tailed p values of <0.05 considered significant. Results: 329 cases were identified. 80.9% women underwent retroperitoneal node dissection, of whom 95.1% underwent pelvic (P) node dissection and 85.3% underwent periaortic (PA) node dissection. Of the women who had nodal dissection, mean age was 65.3 and BMI 31.1. Histology included 33.5% endometrioid, 49.3% serous or clear cell, and 15.4% carcinosarcoma. Stage distribution included 57.6% stage I, 8.0% stage II, 29.8% stage III, and 4.6% stage IV. Of LUS+ cases, 42% (56/132) had nodal metastases, in contrast to 12.7% (17/134) of LUS- cases. Sensitivity of + nodes by LUS was 76.6%, with a specificity of 60.6%, positive predictive value of 42.4%, and negative predictive value of 87.3%. Of LUS+ cases, 49/123 (39.8%) had +P nodes; 27/106 (21.8%) +PA nodes; and 21/100 (21%) had both +P/PA nodes. Of LUS- cases, 15/130 (11.5%) had +P nodes; 7/121 (5.8%) +PA nodes; and 4/121(3.3%) had both +P/PA nodes. Confirming the above findings, when adjusting for myometrial invasion and lymphovascular invasion, overall nodal status, +P nodal status and PA nodal status were independently associated with LUS (p<0.000; p=0.001; p=0.003 respectively). Conclusions: There is debate regarding the utility of lymph node assessment in women with endometrial cancer. However, women with grade 3 endometrial cancer are at high risk for nodal involvement. This information is critical in determining post-operative adjuvant therapy. This data suggests women with grade 3 endometrial cancer, particularly those with lower uterine segment involvement, should undergo routine lymphadenectomy due to the high risk of nodal involvement.
In vitro chemoresponse assay for patients with cervical cancer.
Authors: Del Priore Giuseppe , Grigsby Perry Wayne , Gan Christine M. , Tillmanns Todd D.
Published: March 2020

e15514

Background: Chemotherapy is used in cervical cancer as neoadjuvant, chemosensitization with radiation, and upon recurrence. This study reports the results of an in vitro chemoresponse assay (ChemoFx, Precision Therapeutics) in primary, metastatic, or recurrent cervical cancer. Methods: Between 8/8/06- 6/2/10, 557 tumor specimens were received and 353 (63%) were successfully assayed. Status (primary, metastatic or recurrent) and histology (squamous 58%; adenocarcinoma 20%; adenosquamous 6%; neuroendocrine 5%; and other12%) was confirmed in 273 for this report. Single agents tested included: carboplatin, cisplatin, paclitaxel, docetaxel, epirubicin, fluorouracil, 4-hydroxy ifosfamide, SN-38, topotecan, and vinorelbine. Doublets included carboplatin/paclitaxel (Carbo/Tax) and cisplatin/topotecan (Cis/Topo). Tumor response was determined from dose response curves and scored as responsive (R), intermediate response (IR), or nonresponsive (NR). Chemoresponse is reported as R+IR. Results: 273 tumor specimens were evaluable for response. Chemoresponse of primary cancers (n=151) to single agents was SN-38-75%; 4-hydroxy ifosfamide-71%; topotecan-62%; epirubicin-58%; and cisplatin-58%. Chemoresponse of primary tumors to doublets was 73%-carbo/Tax and 56%-Cis/Topo. Chemoresponse of metastatic cancers (n=66) to single agents was irinotecan-54%; ifosfamide-51%; epirubicin-44%; topotecan-41% and fluorouracil-40%. Chemoresponse of metastatic tumors to doublets was 53%-Carbo/Tax and 30%-Cis/Topo. Chemoresponse of recurrent cancers (n=56) to single agents was epirubicin-44%; ifosfamide-41%; vinorelbine-39%; paclitaxel-39%; and topotecan-36%. Chemoresponse of recurrent tumors to doublets was 46%-Carbo/Tax and 35%-Cis/Topo. Conclusions: In vitro chemoresponse analysis is feasible in cervical cancer. Overall chemoresponsiveness was greater in primary cancers (58%) than in recurrent cancers (35%); (p<0.0001). Chemoresponse to single agent cisplatin was lower than most other single agents in all three patient groups. Since many recurrent patients have prior platinum exposure, a chemoresponse assay will have further study possibilities in this setting.
Impact of the third and subsequent lines of chemotherapy in the cure rate of patients with high-risk gestational trophoblastic neoplasia (HR-GTN).
Authors: Jankilevich Gustavo , Bianconi Maria Ines , Otero Silvina , Alvarez Lucia , Storino Claudio
Published: March 2020

e15521

Background: Successful chemotherapy is the backbone of the treatment of patients with HR-GTN. However a percentage of this patients will recur to first treatment attempt. It is not defined how many lines of chemotherapy are required to achieve complete reponse and wether to continue with different chemotherapy regimens is beneficial for achieving the cure. Methods: We performed a review of medical records of consecutive patients with diagnosis of gestational trophoblastic disease (GTD) and HR-GTN by FIGO-OMS criteria between 1990-2011. All were treated in our hospital. Results: 365 patients were registrated with GTD diagnosis. Thirty-four patients had HRNTG, 23 patients (67.6%) had complete reponse with first and second line chemotherapy (EMA PE and EMA CO). Eight of eleven patients had complete reponse with additional regimens. Three patients died, one due toxicity. The reponse rate of third and more lines was 72%. Overall disease free survival was 91%. Conclusions: In patients with HRNTG three or more lines of treatment achieves the cure in a high percentage of patients. In this setting the therapy should always be with curative intent, regardless of the number of lines required to achieve this objective.
Prognostic value of epithelial cell adhesion molecule (EpCAM) in patients with primary epithelial ovarian cancer.
Authors: Woopen Hannah , Pietzner Klaus , Richter Rolf , Fotopoulou Christina , Joens Thomas , Braicu Ioana , Mellstedt Hakan , Darb-Esfahani Silvia , Denkert Carsten , Sehouli Jalid
Published: March 2020

e15531

Background: EpCAM, a well known cancer antigene is currently experiencing a renaissance in its use as a binding site for targeted oncologic therapy and prognostic marker in various epithelial carcinomas such as breast cancer or carcinomas of the oral cavity. Goal of this retrospective study was to identify EpCAM as a potential prognostic marker for patients with primary epithelial ovarian cancer (EOC). Methods: EpCAM expression was assessed in tumor tissue by immunohistochemistry using the Avidin-Biotin-Complex method on paraffin-embedded ovarian cancer tissue samples. EpCAM overexpression was defined as an expression of EpCAM as high as 76-100%. Clinical data as well as tumor tissue samples were collected within the validated “Tumor bank Ovarian Cancer Network (TOC)”. Results: Seventy-four patients with the primary diagnosis of EOC between 01/1994 and 12/2009 were included in this study. Median age at diagnosis was 56 years. The vast majority of the patients (75.4%) presented an advanced stage disease (FIGO III/IV). Forty-one (55.4%) patients were diagnosed with a serous, 19 (25.6%) a endometrioid and 14 (19%) a mucinous histology. EpCAM was overexpressed in 87.7% of the patients. Serous tumors expressed EpCAM in significantly higher rates than mucinous tumors ( p=0.045). EpCAM overexpression correlated in univariate analysis with a significantly better overall survival. Multivariate analysis including histological subtype identified EpCAM expression of 76-100% to be independently associated with a significantly better overall survival compared to a lower EpCAM expression of ≤50% (p=0.008). Conclusions: EpCAM overexpression in EOC appears to be associated with significantly higher overall survival rates. Larger, prospectively assessed multicenter studies are warranted to further evaluate and confirm these novel findings and possibly establish EpCAM as a potent therapeutic target in EOC.
Analysis of time from initial imaging study to definitive surgical diagnosis in patients with epithelial ovarian malignancies.
Authors: Bickley Thomas , Clegg Eericca , Nash John , Yan Xiaowei (Sherry) , Gogoi Radhika
Published: March 2020

e15536

Background: It is well established that women diagnosed with advanced stage ovarian cancer have a significantly lower five-year survival rate. Often multiple imaging modalities are used in the initial evaluation. This is costly, often unnecessary, and may be a contributing factor to a delay in diagnosis. We sought to evaluate the time from initial imaging study to diagnosis. Methods: After IRB approval, a retrospective chart review was performed utilizing data from the electronic medical record at an integrated health care system. All patients who underwent surgery with a diagnosis of primary peritoneal, ovarian, or fallopian tube cancer between 7/2006 and 8/2011 were included. Data collected included age at time of surgery, number and dates of imaging studies performed within 180 days prior to surgery, primary cancer site, stage, and histology. Patients were excluded for recurrent disease, studies without dates, or imaging studies performed greater than 180 days prior to diagnosis. Statistical analysis was performed using the Cox Proportional Model. Results: A total of 146 patients were included in the study. The average number of imaging studies was 1.7 and the average time to diagnosis from initial imaging was 33.5 days. Time to diagnosis was shorter if patients ever had a CT scan (29.3 vs 73.3 days; P<0.001), and longer if patients ever had an ultrasound (40.4 vs 27.8 days; P=0.02). There was no difference in the overall number of imaging studies performed when controlling for stage <3C vs >3C. However, time to diagnosis was significantly less (29.1 vs 45.1 days; P=0.01) for more advanced stage disease. There was no difference in time to diagnosis or overall number of imaging studies performed when controlling for primary cancer site or age. Conclusions: The data suggest that performing a CT scan as the only imaging modality results in a significantly shorter time to diagnosis than when ultrasonography is included in the initial evaluation. Of patients who initially got an ultrasound most ultimately went on to have a CT scan, likely increasing the interval to diagnosis. We suggest that implementing an adnexal mass algorithm may allow patients quicker access to definitive diagnosis and treatment.
Radiation with cisplatin or carboplatin for locally advanced cervix cancer: The experience of a tertiary cancer center.
Authors: Au-Yeung George , Mileshkin Linda R. , Bernshaw David , Kondalsamy-Chennakesavan Srinivas , Rischin Danny , Narayan Kailash
Published: March 2020

e15541

Background: Definitive treatment with concurrent cisplatin and radiation is the standard of care for locally advanced cervical cancer. The optimal management of patients with a contraindication to cisplatin has not been established. We conducted a retrospective audit of the impact of concurrent chemoradiation in a cohort of patients (pts) with locally advanced cervical cancer. Methods: All pts with locally advanced cervical cancer treated with definitive radiation were entered into a prospective database. Information regarding their demographics, stage, histology, recurrence and survival were recorded. Pharmacy records were reviewed to determine concurrent chemotherapy use. The primary endpoint was overall survival, and secondary endpoints were disease free survival and rates of primary, nodal or distant failure. Univariate and multivariate analyses were performed, incorporating known prognostic factors of age, FIGO stage, uterine body involvement, tumour volume on MRI and nodal involvement. Results: 442 pts were treated from Jan 1996 to Feb 2011. Median age was 59 (range 22-94); 89% had squamous histology and 64% node-negative disease. 269 pts received cisplatin, 59 received carboplatin because of a contraindication to cisplatin and 114 received no concurrent chemotherapy (most prior to 1999). Overall survival adjusted for other prognostic factors was significantly improved with use of concurrent cisplatin compared to radiation alone (HR 0.53, p=0.001), as was disease free survival and the rate of distant failure. Use of concurrent carboplatin was not associated with any significant benefit compared to radiation alone in terms of overall survival or disease free survival on univariate or multivariate analyses. Conclusions: The results of this audit are consistent with the known significant survival benefit with concurrent cisplatin chemoradiation. However, there did not appear to be any significant benefit associated with concurrent carboplatin although there are potential confounding factors in this small cohort. The available evidence in the literature favors the use of non-platinum chemotherapy rather than carboplatin in pts with contraindications to cisplatin.
Platinum-based combinations as first-line chemotherapy in advanced, persistent, or recurrent cervical cancer.
Authors: Limareva Svetlana Vladimirovna , Khokhlova Svetlana Victorovna , Odintsova Anastasiya Sergeevna , Cherkasova Marina Valerievna , Vinogradova Liliya Igorevna , Gorbunova Vera A.
Published: March 2020

e15543

Background: Platinum compounds are the most active agents in cervical carcinoma. The aim of this study was to evaluate the activity and toxicity of platinum-based chemotherapy as first line treatment in patients with advanced/recurrent cervical cancer. Methods: Since 2005 to 2011years 68 pts were include in the pilot study. Patients with histological proven primary carcinoma, measurable tumors, age ≥ 18, PS of 0-1, adequate bone marrow, renal and hepatic functions were eligible for this trial. Prior chemotherapy was allowed only in the context of radiosensitization. Treatment consisted of 2 modes: PC - paclitaxel 175 mg/m2 3-h I.v. + cisplatin 75 mg/m2 or carboplatin AUC-6 ( 6 pts)- d1x 21d; IC – irinotecan 65 ìg/m2 + cisplatin 40 mg/m2 on d 1 and 8 x 21 d. Responses were assessed using RESIST. Results: 68 pts were identified. There were no differences between the groups in terms prior radiation or radiochemotherapy. Group PC: 28 pts were included. Efficacy and toxicity was available for 27. Two pts continue treatment. Median age 43,5 years (range 28-69). The ORR was 55.5% (CR - 5(18.5%) and PR -10(37.0%)). 8 pts (29.6%) SD and 4 (14.8%) PD. The median TTP was 7 months. Overall, 148 cycles were administered with a median of 5 (range 2-8) cycles. Major toxicities were as follows: GIII and GIV neutropenia in 22.2% and 11.1% pts; GIII anemia - in 2 pts; GI-II neuropathy in 45.9% pts. G III nausea/vomiting were in 3 pts (11.1%). Group IC: 40 pts were included, 38 were available for efficacy. Median age 49,8 years (range 25-67). The ORR was 47.3% (5 CR(13.2%) and 13 PR (34.2%)). 13 (34.2%) pts had SD and 7 (18.4%) - PD. The median TTP was 6 months. All 40 pts receved 254 cycles ( median 6.3 (range 1-11) cycles. GIII and IV neutropenia were in 40% and 10% pts; GIII anemia in 20% pts. G I-II neuropathy and G I-II diarrhea in 15% pts and 30%pts. G IV of diarrhea observed in 1 pt. GIII-IV nausea and vomiting were in 20% and 15%pts. There were no statistical differences in clinical outcome (OR(p= 0,69) and TTP(p=0,65)) between these 2 platinum-based regimes. Conclusions: Our data indicate that both regimes had high efficacy and well tolerated as first line treatment in patients with advanced/recurrent cervical cancer. The randomized study is necessary.
Use of liposome encapsulated doxorubicin citrate (LEDC) as a valid drug in patients affected by ovarian cancer suffering from chemotherapy side-effects.
Authors: Angelucci Michela , Plotti Francesco , Muzii Ludovico , Terranova Corrado , De Cicco Nardone Carlo , Montera Roberto , Damiani Patrizio , Cafà  Ester Valentina , Dugo Nella , Guzzo Federica , Ricciardi Roberto , Aloisi Alessia , Luvero Daniela , Miranda Andrea , Capriglione Stella , Lopez Salvatore , Scaletta Giuseppe , Linciano Francesca , Benedetti Panici Pierluigi , Angioli Roberto
Published: March 2020

e15547

Background: Doxorubicin had a wide spectrum of cytotoxic activity in gynecological cancer. Moreover, this drug is associated with chronic cardiac toxicity, often irreversible, which limits lifetime dose. A new liposomal formulations has been developed in the past decades to limite side-effects of doxorubicin: liposome encapsulated doxorubicin citrate (LEDC). In this study we report our experience with LEDC in patients affected by advanced/recurrent gynaecological cancer, suffering from chemotherapy side effects. Methods: From 2000 to December 2008, 43 patients who showed palmoplantar erythrodysesthesia (PPE) during adjuvant or palliative setting treatment of metastatic/recurrent epithelial ovarian cancer. All patients enrolled in the study were treated with liposomal encapsulated doxorubicin citrate (LEDC), administered at the dose of 50 mg/mq every 3 weeks until disease progression or adverse effects. Results: We have enrolled 43 patients who suspended previously chemotherapy treatment for severe PPE. A total of 32 patients completed planned 6 cycles of chemotherapy. After 6 cycles of chemotherapy 3 out of 43 patients (6%) continued to show a complete response, 9 patients (20%) maintained partial response, 16 patients (37%) showed stable disease and 4 patients (9%) suffered disease progression. No severe G3–G4 hematologic toxicity was showed, but neutropenia and anemia continued to be the most common side effects. No cutaneous toxicity were reported. Conclusions: LEDC is a well tolerated drug and a valid alternative in patients affected by ovarian cancer suffering from cutaneous toxicity by other drugs.
Advanced endometrial cancer: Is there a benefit to neoadjuvant therapy?
Authors: Czok Sarah , Zechmeister Jenna R. , Jewell Andrea , Boyd Leslie R.
Published: March 2020

e15548

Background: The majority of endometrial cancers present as early stage tumors, yet those that are advanced at diagnosis are associated with poor outcomes. The role of radical debulking surgery for endometrial cancer is not clear. However, the use of neoadjuvant chemotherapy is also unproven. We sought to evaluate if utilizing neoadjuvant chemotherapy for advanced endometrial cancer affected outcomes. Methods: A retrospective review from two hospitals served by one academic center from 2002 to 2011 was performed. All patients with stage 3 or 4 disease were identified. Patients with non-epithelial cell types, including carcinosarcoma, were excluded. Patients who received neoadjuvant treatment prior to surgery were identified. A case-control design was utilized matching patients 1:3 or 1:4 stratified by age, stage, grade, histology and performance status. Descriptive statistics and nonparametric analyses were utilized. Results: A total of 115 patients with advanced endometrial cancer were identified. 19 were excluded due to wrong cell type and 1 due to stage 3 disease based on positive cytology. 6 patients had a neoadjuvant treatment approach (NAs). 20 patients were identified as matched controls (CTRLs). The average age was 61 for the NAs, and 63 for the CTRLs. The average BMI was 26.9 for the NAs, and 27.4 for the CTRLs. NAs were more likely to have stage 4 disease—5/6 NAs versus 5/20 CTRLs. Both groups had a high proportion of grade 3 tumors—4/6 NAs versus 15/20 CTRLs. The performance status was similar in both groups. The median number of chemotherapy cycles was 11 in the NAs, and 4 in the CTRLs. 18/20 CTRLs received adjuvant treatment, and 17 included systemic chemotherapy. In the NAs, with a median follow-up of 17 months, 4 were alive with disease (AWD) and 2 were dead of disease (DOD). In the CTRLs, with a median follow-up of 14 months, 7 patients were NED, 8 were AWD, and 5 were DOD. Conclusions: Despite a small sample size, our results indicate that primary surgery remains the preferred strategy for patients with advanced endometrial cancer. However, prospective data is needed to determine to what extent neoadjuvant chemotherapy affects outcomes.
Use of carboplatinum as neoadjuvant setting for patients affected by locally advanced cervical cancer.
Authors: De Cicco Nardone Carlo , Plotti Francesco , Angelucci Michela , Montera Roberto , Damiani Patrizio , Cafà  Ester Valentina , Guzzo Federica , De Oronzo Maria Antonietta , Montone Eva , Ricciardi Roberto , Aloisi Alessia , Luvero Daniela , Portuesi Rosa Alba Valentina , Scaletta Giuseppe , Capriglione Stella , Lopez Salvatore , Miranda Andrea , Gennari Paolo , Benedetti Panici Pierluigi , Angioli Roberto
Published: March 2020

e15553

Background: The aim of this study is to evaluate the efficacy and safety of the combination of carboplatin and paclitaxel as neoadjuvant chemotherapy (NACT) in patients affected by locally advanced cervical cancer. Methods: Between June 2007 to May 2009, all patients with diagnosis of IB2-IIB cervical cancer were considered eligible for this protocol. All enrolled patients received 3 cycles of carboplatin (AUC6) and paclitaxel at 175 mg/mq in neadjuvant setting. The chemotherapy induced toxicity and response to the treatment were evaluated according to World Health Organization criteria. Results: We have enrolled 23 patients with diagnosis of locally advanced cervical cancer. A total of 22 patients completed planned 3 cycles of neoadjuvant chemotherapy. After 3 cycles of chemotherapy 9 out of 23 patients (42%) showed a complete response, 7 patients (35%) partial response, 5 patients (16%) stable disease and 2 patients (11%) showed disease progression. The most common toxicity was haematologic (43%), extra haematologic toxicities were nausea/vomiting, neuropathy and alopecia, that occurred in 45%, 13% and 25% respectively. No renal and grade 3 and 4 haematologic toxicities were registered. Conclusions: Our results suggest that the use of carboplatin, in neadjuvant setting, is a well tolerated drug, produces manageable toxicity with a response rate similar to standard cisplatin. Then, it rappresents a valid alternative in patients affected by locally advanced cervical cancer.
Lower-limb drainage mapping for lymphedema risk reduction after pelvic lymphadenectomy for endometrial cancer.
Authors: Bats Anne-Sophie , Nos Claude , Bensaid Cherazade , le Frere-Belda marie-Aude , Collignon Marie-Anne , Faraggi Marc , Lecuru Fabrice
Published: March 2020

e15558

Background: Pelvic lymphadenectomy is associated with a significant risk of lower-limb lymphedema. In this proof-of-concept study, we evaluated the feasibility of identifying the lower-limb drainage nodes (LLDNs) during pelvic lymphadenectomy for endometrial cancer. Secondary objectives were to map lower-limb drainage and to assess the diagnostic value of our mapping technique. Methods: Prospective study of patients with endometrial cancer requiring pelvic lymphadenectomy, with no neoadjuvant radiotherapy or chemotherapy and no history of lower-limb surgery. A radiopharmaceutical was injected into both feet on the day before surgery. LLDNs were identified using preoperative lymphoscintigraphy and intraoperative isotopic probe detection then removed before complete pelvic lymphadenectomy. LLDNs and pelvic lymphadenectomy specimens underwent separate histological analysis. Results: Of the 12 patients with early-stage endometrial cancer, 10 underwent preoperative lymphoscintigraphy, which consistently identified inguinal, femoral and pelvic LLDNs. The intraoperative detection rate was 83% (10/12). The 2 patients with no LLDNs detected intraoperatively had lymphoscintigraphy-detected LLDNs. Median number of hot nodes per patient was 5 (3-7) on the right and 3 (2-6) on the left. Of 107 LLDNs, 106 were in the external iliac area, including 38 in the lateral group and 45 in the intermediate and medial groups. None of the patients had node metastases at any site. No early complications related to the technique occurred. Conclusions: Our mapping technique appears feasible, safe, and associated with a high LLDN identification rate. LLDN mapping may allow the preservation of LLDNs, thereby decreasing the risk of lower-limb lymphedema and improving quality of life.
A proteomic analysis of surgical cytoreduction in patients with advanced ovarian cancer.
Authors: Lesnock Jamie L , Hood Brian L , Sun Mai , Bhargava Rohit , Conrads Thomas P , Krivak Thomas C.
Published: March 2020

e15560

Background: Optimal surgical cytoreduction (<1 cm residual tumor) has been shown to improve overall survival compared to suboptimal (>1cm) debulking as primary treatment for advanced stage epithelial ovarian cancer (EOC). Molecular descriptions of optimally and suboptimally debulked ovarian tumors are lacking. We have performed a global, quantitative proteomic analysis of optimally and suboptimally debulked EOC tumor samples. Methods: A cohort of 16 optimally (8) and suboptimally (8) debulked patients with archival formalin-fixed, paraffin-embedded tumor specimens was identified. Homogenous tumor cell populations were collected and protein digests were prepared and analyzed by high resolution mass spectrometry for identification and quantification by spectral counting. Immunohistochemistry (IHC) was performed and slides were scored using a semi-quantitative method (H-score). Results: An average of 1,110 proteins were identified within each cohort, of which 21 possessed significant (p<0.05) differential abundances. Specifically, three proteins (annexin A1, S100-A11, and synuclein-gamma, or SNCG) which have significant roles in cell migration and cancer biology were identified. Although no H-score was statistically significant, comparison of positively-staining cells for SNCG showed a trend toward increased expression in suboptimally debulked patients, p=0.08. Conclusions: Overexpression of SNCG has been shown to be predictive of worse prognosis in papillary serous uterine cancer cell lines, and increased expression of SNCG in breast cancer correlates with advanced stage and aggressiveness of disease. Our data suggest SNCG may have similar predictive value in EOC, as tumors with elevated levels of this protein may be less amenable to optimal cytoreduction.
Expression of ERCC1 protein (excision repair cross complementing group 1) in patients with invasive carcinoma of the uterine cervix (CC) undergoing definitive chemoradiation (CR).
Authors: Caires Inacelli Queiroz de Souza , Caires-Lima Rafael , Colombo Renata , Ramos Clarissa CA , Machado Karime Kalil , Siqueira Sheila Aparecida Coelho , Carvalho Heloisa de Andrade , Fukushima Julia Tizue , Adra Thais Rodrigues , Hoff Paulo M. , Estevez-Diz Maria Del Pilar
Published: March 2020

e15562

Background: CC is the leading cause of cancer death among women in developing countries. ERCC1 protein participates in DNA repair through the nucleotide excision repair pathway, involved in resistance to platinum-based chemotherapy. Its value as a predictive marker of tumor response to treatment, progression or death is still unknown. We evaluated ERCC1 protein expression and clinical variables as a predictive marker of progression-free survival (PFS) and overall survival (OS) in patients (pts) with CC submitted to CR. Methods: Retrospective data analysis of pts with histological diagnosis of CC, treated with CR between 2004-2009. Platinum-based chemotherapy was administered weekly (x6) concurrent to external beam radiotherapy (EBRT) to the pelvis (39.6 – 45.0 Gy), parametrial boost (14.0 – 20.0 Gy) when indicated and high-dose rate brachytherapy (HDR) (28.0 – 30.0 Gy). ERCC1 expression was assessed by immunohistochemistry (IHC). Results: We analyzed 75 pts, median age was 55 years (range 24-76), the performance status (PS) was 0 or 1 at baseline in 50 pts (66%) and 63 had squamous histology (84%). Thirty-two were stage IIB (43%) and 19 were IIIB (25%). Sixty-five patients received cisplatin 40mg/m2/w (87%) and 9, carboplatin AUC2/w (12%), median of 6 cycles (range 2-9). Median RT and HDR doses were 59.4 Gy (range 40.4 to 60.3) and 28.0 Gy (range 14.0 – 37.5), respectively. Thirty-two pts were available by ERCC1 IHC and all expressed the marker. Median PFS and OS were 35.5 (95% CI – 13.8 - 57.6) and 81 (95% CI- 21.2 - 140.8) months, respectively. In multivariate analysis, receiving < 6 chemotherapy cycles and baseline Hb <10.0 were correlated with disease progression and death, HR 0.302; p 0.011 (95% CI- 0.012-0.762) and HR 0.6; p 0.00 (95% CI- 0.474 – 0.760), respectively. PS at baseline did not correlate with PFS or OS, HR 0.985; p 0.614 (95% CI 0.930 – 1.044). Conclusions: In this population, since all pts expressed the protein, ERCC1 expression couldn't discriminate patients who most benefit from CR. Interestingly, a minimum of 6 chemotherapy cycles and a baseline Hb ≥ 10.0 seem to have a prognostic value.
Anticancer efficacy of the combination of low-dose cisplatin and trichostatin A or 5-aza-2’-deoxycytidine in ovarian cancer cells.
Authors: Meng Fanliang , Sun Guigin , Zhong Mei , Yu Yanhong , Brewer Molly
Published: March 2020

e15563

Background: We investigated the combination of low dose cisplatin with histone deacetylase inhibitor trichostatin A and methyl transferase inhibitor 5-aza-2’-deoxycytidine to determine if these agents could improve the sensitivity of ovarian cancer cell lines to cisplatin. The goal was to improve efficacy and decrease the toxicity of conventional chemotherapy in human ovarian cancer. Methods: Two chemoresistant ovarian cancer cell lines HEY, SKOV3 and one immortalized cell line IOSE were were treated with increasing doses of each drug alone and in combination to determine optimal cytotoxicity at the lowest dose. Markers of adhesion, metastasis, proliferation, self renewal, and measures of epigenetic regulation were measured. Spheroids, treated with single and combination drugs, were measured for cell viability. SCID mice were injected with pretreated cells and with untreated cells and then treated sequentially. Results: TSA or 5-aza-2’-deoxycytidine combined with Cisplatin had a marked reduction in E-cadherin and N-cadherin (adhesion and migration), proliferation protein Akt and Akt-1, self-renewal markers Oct4/Nanog/Sox2, and the drug transporter ABCG2. DNA methylase, DNMT3a/3b, histone deacetylase HDAC1/2 and histone demethylase LSD1, measures of epigenetic regulation, were suppressed with combined treatment. Histone methylation markers H3K4 and H3K9 were regulated differentially, with the trimethyled-H3K9 significantly suppressed, suggesting bivalent chromatin regulation. Cisplatin/TSA suppressed spheroid formation, growth, and viability. Cisplatin/TSA suppressed tumorigenesis in SCID mice when cells were pretreated. Animals treated after tumor formation with epigenetic modifiers followed by cisplatin achieved significant tumor regression, suggesting that both approaches enhance anticancer effects. Conclusions: Our research suggests the combination of low dose cisplatin with epigenetic modifiers administered together or sequentially may be promising treatments for ovarian cancer with reduced toxicity and may reverse platinum resistance.
Serum concentration of VEGF, sFLT-1, and CD105 in patients with endometrial carcinoma.
Authors: Maenpaa Johanna , Saarelainen Sami Kristian , Peltonen Nina , Lehtimaki Terho , Vuento Maarit
Published: March 2020

e15564

Background: Preoperative evaluation of the risk for metastases in endometrial carcinoma is challenging. The aim of this study was to compare preoperative serum levels of angiogenetic markers VEGF, sFLT-1, and CD105 (endoglin) in predicting a metastasized disease. Methods: Preoperative sera from 100 consecutive patients diagnosed for endometrial carcinoma were collected. The serum concentrations of VEGF, sFLT-1, and CD105 were assessed by enzyme-linked immunosorbent assay (ELISA). The results were correlated to the presence of metastases, presence of deep (≥50%) myometrial invasion and histologic grade of the tumor. Cases with other than endometrioid histology were excluded from the study. Results: Eleven patients had a metastasized disease (≥Stage IIIA, FIGO 2009 classification). The serum concentration of VEGF was higher in the group with metastases (median [range] 394 pg/mL [31-1524 pg/mL] vs. 801 pg/mL [631-1183 pg/mL], p=0.001). The concentrations of sFLT-1 and CD105 did not show statistical difference between the two groups. In the multivariable analysis, the concentration of VEGF was the sole independent factor for the presence of metastases (OR 1.003, 95% CI 1.000-1.005, p=0.019). Conclusions: Preoperative serum VEGF concentration correlates with the presence of metastases in endometrioid endometrial carcinoma.
Primary debulking surgery (PDS) for stage IIIc ovarian cancer: Quo vadis?
Authors: Garrett Leslie A. , Growdon Whitfield Board , Boruta David M. , del Carmen Marcela G , Priebe Anna M. , Goodman Annekathryn , Bradford Leslie , Clark Rachel Marie , Schorge John O.
Published: March 2020

e15568

Background: The efficacy of PDS for advanced ovarian cancer has recently been challenged by data suggesting equivalent clinical outcomes for neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS). The strongest known predictor of prolonged survival in either group is the ability to achieve complete resection (CR) to no residual disease. PDS that results in a CR is associated with the longest overall survival of any sequence of treatment. The aim of this study was to determine what type of surgical approach is required to successfully perform PDS. Methods: All women with newly diagnosed stage IIIC epithelial ovarian carcinoma treated at our institution from 2000 to 2010 were identified. Pathology was prospectively reviewed by a faculty gynecologic pathologist. Treatment planning was discussed and documented at our weekly multidisciplinary tumor board conference. Data was retrospectively extracted from computerized medical records. Results: 344 (86%) of 401 women underwent PDS. Optimal debulking was achieved in 278 patients (81%): 35% had CR while 46% had 0.1-1.0 cm residual disease. 56 stage IIIC pts (19%) had a suboptimal surgical outcome with ≥ 1.0 cm. Compared to those having a CR, patients with 0.1-1.0 cm residual were more likely to require splenectomy (17 v 5%; P = 0.002) and transverse colectomy (19 v 10%; P = 0.042), with comparable rates of rectosigmoid resection (41 v 39%; P = 0.712) and en bloc pelvic resection including total peritonectomy (26 v 30%; P = 0.050). Patients undergoing CR were more likely to have diaphragmatic surgery (31 v 20; P = 0.068) and lymphadenectomy (67 v 33%; P < 0.001). Conclusions: PDS is the preferred treatment of stage IIIC epithelial ovarian cancer at high-volume centers demonstrating >75% rates of optimal cytoreduction. Tumor biology may lead to the need for more aggressive upper abdominal procedures in patients with 0.1-1.0 residual. Diaphragm resection, stripping or ablation is more often required in order to achieve CR. Since subclinical macroscopic nodal metastases are often present, lymphadenectomy is also frequently performed to ensure that all possible disease has been resected.
Diagnostic value of FDG-PET/CT for peritoneal carcinomatosis (PC) before hyperthermic intraperitoneal chemotherapy (HIPEC) in ovarian cancer.
Authors: Razzouk-Cadet Micheline , Zwarthoed Colette , Desantis Mariangela , Viau Philippe , Mahamat Abakar , Mounier Nicolas , Bereder Jean Marc
Published: March 2020

e15574

Background: Evaluate FDG-PET/CT utility for the detection of peritoneal carcinomatosis from ovarian cancer treated by chemotherapy by using surgical and histopathological findings as the standard of reference. Methods: 38 patients (46 to 68 years) with recurrent (n=35) or primary (n=3) ovarian cancer were reviewed for the presence of peritoneal lesions on FDG-PET/CT before cytoreductive surgery and HIPEC treatment. 30 had adenocarcinomas (13 papillary serous, 7 moderately differenciated, 6 poorly differentiated, 3 serous and 1 serous cystadenocarcinoma) and 2 endometrioid tumors. 9 had psammomatous calcifications. All were suspected cases of PC. 35 patients had received adjuvant chemotherapy and 3 neoadjuvant chemotherapy (primary cancer). FDG-PET/CT results were reinterpreted by two experienced nuclear medicine physicians who knew that PC was suspected. The FDG uptake was determined as SUVmax in the most active lesion in all abdomino-pelvic quadrants (average SUVmax= 6.1; range 1.1- 25). SUVmax in the liver was also measured (average SUVmax=2.9). All PET/CT exams were realised on the same machine. Results: FDG PET/CT diagnosed 18 in 32 patients with peritoneal metastases. There was no suspicious site of abnormal FGD uptake in the supradiaphragmatic regions. The sensitivity, specificity and accuracy of FDG PET/CT were respectively 59,100, 66%. The positive and negative predictive value of FDG PET/CT were 100 and 31%. 13 false negative PET/CT findings were due to millimetric or infracentimetric perihepatic, mesenteric and omental implants (unseen on PET/CT) and to nodules less than one centimeter with no significant FDG uptake (SUVmax lower than hepatic uptake). The true negative findings were found after chemotherapy. Conclusions: FDG-PET/CT can be considered as a useful tool for the selection of patients for HIPEC treatment in the absence of distant metastasis. It showed excellent results for the positive diagnosis and tumor burden for lesions more than 1 cm (PPV 100%). The sensitivity was low in the presence of millimetric disease with or without prior chemotherapy before HIPEC.
Metastatic parathyroid carcinoma: Treatment modalities illustrated with a case report.
Authors: White Alison Marie , Bowyer Samantha Elizabeth , Davidson John Andrew , Ransom David
Published: March 2020

e16004

Background: We report a case of inoperable metastatic parathyroid carcinoma with life-threatening hypercalcaemia. We achieved rapid control of calcium with denosumab. Methods: Our patient presented with complications of hyperparathyroidism. He underwent a partial parathyroidectomy and hemithyroidectomy. Parathyroid carcinoma was confirmed. There was no metastatic disease. A year later he was hypercalcaemic, 4.15 mmol/L (2.15-2.60 mmol/L), with elevated PTH and creatinine. FDG activity was seen on PET at the thyroid bed and retrocrural space. Extensive pleural metastases limited resection to debulking. The calcium and PTH remained elevated. Hydration and zoledronic acid had little effect. Cinacalcet 90mg QDS led to no improvement in calcium. Weekly zoledronic acid was used to keep his calcium below 4 mmol/L. Two cycles of cyclophosphamide, 5-flurouracil and dacarbazine led to no decline in the calcium. Denosumab is a fully human monoclonal IgG2 antibody with a high affinity and specificity to bind RANK ligand, mimicking Osteoprotegerin, competitively blocking the binding of RANK to its ligand to inhibit osteoclast activation. Results: 120mg was given subcutaneously. By day 8 the calcium had dropped to 2.66 mmol/L. After a second dose, the calcium was 2.33 mmol/L. Bone turnover markers were rapidly suppressed. The calcium was in the normal range for four months with improved renal function. Further denosumab will be guided by serum calcium. Conclusions: Parathyroid carcinoma is rare. The mainstay of treatment is resection, even in metastatic disease. Often the disease is refractory to medical management leading to complications of hypercalcaemia. There is limited evidence for chemotherapy and few strategies to manage resistant hypercalcaemia have been published. In this case refractory hypercalcaemia dramatically responded to denosumab. Denosumab does not require dose adjustment for renal impairment, a common finding with hypercalcaemia. In this case denosumab offered prolonged control of serum calcium. We propose that denosumab should be considered for patients with hypercalcaemia due to parathyroid cancer.
Assessment of the life quality in head and neck cancer patients.
Authors: Atasever Akkas Ebru , Yucel Birsen , Kilickap Saadettin , Okur Yillar , Kacan Turgut , Eren Mehmet Fuat , Babacan Nalan Akgul
Published: March 2020

e16005

Background: In this study, we aimed to investigate the effect of radiotherapy on the life quality in head and neck cancer patients. Methods: Between 2007 and 2010 years, 82 head and neck cancer patients who had taken radiotherapy at Cumhuriyet University Department of Radiation Oncology were assessed at the beginning, midline of the treatment and 1 and 6 months after radiotherapy with European Organization for Reseach and Treatment of Cancer Ouality of Life Questionnaire Head and Neck Module (EORTC QLQ-H&N35). Wilcoxon sign test were used in the statistical analysis in SPSS version 15.0. Results: Seventy two (%88) men, 10 (%12) women; were analyzed. The median age of the patients was 57 (20-80). Squamous cell carcinoma was the most frequently seen case in 69 (%84) patients. The distribution of the patients according to the localization: larynx carcinoma in 37 (%45) patients, oral cavity tumor in 21 (%26) patients, nasopharynx carcinoma in 14 (%17) patients, paraphypopharynx in 8 (%10) patients and primary unknown in 2 (%2) patients were present. All the symptom scores were affected negatively at the midline, the end, 1 mount after radiotherapy than before the radiotherapy. Pain, swallowing, speech, social eating, social contact, less sexuality, feeling ill, weight loss, weight gain of the symptoms scale scores showed significant improvement at 6 months after the radiotherapy (p<0,05). However it was seen that senses, teeth problems, dry mouth, sticky saliva were affected negatively in the 6th month of radiotherapy than the beginning. Conclusions: In radiotherapy, the life quality of the patients has significantly degraded during the treatment and 1 month after the treatment. However after six months, all the symptom scales were measured as in the beginning. [Table: see text]
Experience of cetuximab in the salvage treatment for recurrent/metastatic oral squamous cell carcinoma.
Authors: Lin Jin-Ching , Liu Shih-An , Wang Chen-Chi , Wang Ching-Ping
Published: March 2020

e16006

Background: We investigated the efficacy, toxicity, and prognostic factors of salvage chemotherapy plus cetuximab in patients with recurrent/metastatic oral squamous cell carcinoma (OSCC). Methods: A total of 30 patients with recurrent/metastatic OSCC were treated by an outpatient weekly multi-drug combination chemotherapy plus cetuximab 400 mg/m2 loading in day 1, then 250 mg/m2 every week. The major chemotherapy regimen consisted of MEMOCLUB (methotrexate 30 mg/m2 d1, epirubicin 30 mg/m2 d1, alternating with mitomycin-C 4 mg/m2 d8, oncovin 1 mg/m2 d8, cisplatin 25 mg/m2 d8, leucovorin 120 mg/m2 d8, 5-fluorouracil 1000 mg/m2 d8, and bleomycin 10 mg/m2 d8) or GV (gemcitabine 1000mg/m2 d1, and vinorelbine 25 mg/m2 d8). Results: Baseline characteristics are as followings: median age=45 (range 32-73); male/female=28/2; Karnofsky performance status 80%/70%/60%/50%=7/18/3/2. Most patients had heavily treated history — first recurrence in 11 cases, second recurrence in 6, and third or more recurrence in 13. The disease extent consists of 25 (83.3%) locoregional recurrences, 3 (10.0%) distant metastasis, and 2 (6.7%) locoregional + metastatic diseases. Grade 3/4 toxicity included leucopenia (46.7%), anemia (33.3%), thrombocytopenia (6.7%), mucositis (6.7%) and skin rashes (20.0%). We obtained a high overall response rate of 66.7% (7 CR, 13 PR, 6 SD, 3 PD, and 1 unevaluable). So far, there are 22 deaths and 8 alive. The overall survival time ranges from 48-1365 days with a median of 312 days. One-year overall survival rate is 49%. Two favorable prognostic factors were found by univariate analysis- disease extent (locoregional vs. distant disease, HR=0.1509, 95%CI=0.0008-0.0592) and tumor response (CR+PR vs. SD+PD, HR=0.2255, 95%CI=0.0277-0.2984). Conclusions: Cetuximab plus weekly outpatient multi-drug chemotherapy has a high response rate and encouraging survival with acceptable toxicity in recurrent/metastatic OSCC patients.
Recombinant adenoviral human p53 gene combined with chemoradiotherapy in treatment of advanced unresectable head and neck cancer.
Authors: Shu Jihong
Published: March 2020

e16011

Background: In head and neck cancer, p53 mutations are present in up 60% of head and neck cancers. Studies indicated p53 gene could increase both radio- and chemo-sensitivities. In this study, we investigate the effectiveness of recombinant adenoviral human p53 gene (rAd-p53) combined with chemoradiotherapy in treatment of advanced unresectable head and neck cancer. Methods: From May 2008 to Dec. 2011, 48 patients with an advanced unresectable head and neck cancer, 29 males and 18 females with an average of 61.3 years old, were included this study. Those patients were treated with intratumoral injection of rAd-p53 at a dose 1-3 ×1012 viral particles (VP) , once every 3 days for 6 times. Chemotherapy regimen consisted of cisplatin 60 mg/m2 on d1 and 5-Fu 600 mg/m2 on d1-5, given intravenously every 3 weeks for 3 cycles. Radiation were given at a dose of 2Gy/f, five fractions a week for a total dose 50~70Gy. Patients were monitored for response, long-term efficacy and adverse events. Results: The median follow-up time was 21.2 months (6~39 months). Overall response rate was 91.7% (44/48), 47.9% (23/48) of complete responses and 43.8% (23/48) of partial responses. One-year overall survival was 79.2% and local progression-free survival was 70.8%. At the last follow-up, the overall survival was 72.9%. Forty-six patients experienced self-limited fever after administration of p53. Conclusions: rAd-p53 gene therapy as a component of comprehensive treatment for advanced unresectable head and neck cancer showed significant beneficial effects.
Identification of a new mutation in the EGFR ligand-binding domain: Predictive factor for cetuximab antitumor activity in head and neck carcinoma?
Authors: Rixe Olivier , Ya-Qin Li , Wise-Draper Trisha , Deng Li , Wang Jiang , Darnell Colleen Marie , Salkeni Mohamad Adham , Wilson Keith , Wells Susanne I , Stambrook Peter , Bahassi El Mustapha
Published: March 2020

e16017

Background: Cetuximab is an EGFR-blocking antibody that has been approved for the treatment of patients with head and neck squamous cell carcinoma (HNSCC) and metastatic colorectal cancer, but no predictive biomarkers of cetuximab activity have yet been identified. Methods: We report on a patient with HNSCC who had a complete tumor regression following treatment with cetuximab given as a single agent after initial surgery and radiation therapy. The EGFR protein expression level, gene copy number and sequence were assessed from both normal and tumor tissues from this patient. Results: Besides protein overexpression and gene amplification in the tumor tissue, sequencing of the EGFR gene from the patient revealed the presence of two somatic mutations, one in the kinase domain (R705G) and the other in the ligand binding domain (P546S). Cells that stably express these EGFR mutants were treated with cetuximab and their sensitivity to the drug was compared to cells expressing the wildtype gene. While the P546S mutation sensitized NIH-3T3 cells to cetuximab, R705G had a marginal effect. The double mutant (P546S/R705G) behaved the same as the P546S mutant, indicating that the mutation in the kinase domain does not contribute to the increased sensitivity to cetuximab. No mutations were found in K-RAS or B-RAF genes and there was no indication that the tumor was HPV-positive. Conclusions: Our results support a role for the P546S mutation in cetuximab sensitivity. To our knowledge, this is the first report of a somatic mutation in the EGFR ligand binding domain that may contribute to increased sensitivity to cetuximab. Other factors including EGFR copy number, EGFR over-expression and the immune response, as indicated by a very adverse side effect that correlated with the antitumor activity, may have also contributed to the observed response. It remains to be determined how frequently this mutation occurs in patients with HNSCCs and other cancers. Prospective evaluation of cetuximab anti-tumor activity in patients harboring P546S mutation needs to be clinically evaluated.