bluuebunny/crossref_metadata_2025 huggingface dataset:
The prognostic significance of supradiaphragmatic lymphadenopathy identified on preoperative computed tomography scan in patients undergoing primary cytoreduction for advanced stage epithelial ovarian cancer
Authors: Kolev V. , Mironov S. , Mironov O. , Moskowitz C. , Ishill N. M. , Gardner G. J. , Levine D. A. , Hricak H. , Barakat R. R. , Chi D. S.
Published: August 2020

e16512

Background: It has been hypothesized and shown in animal studies that the supradiaphragmatic lymph nodes serve as the principal nodes for lymphatic drainage of the entire peritoneal cavity. The purpose of this study was to determine the prognostic significance of enlarged supra-diaphragmatic nodes noted on preoperative computed tomography (CT) scan in patients with advanced epithelial ovarian cancer (EOC). Methods: We performed a retrospective chart review of all patients (pts) with FIGO stage III and IV EOC who had preoperative CT scans of the supradiaphragmatic region and primary cytoreductive surgery at our institution between 1997 and 2004. All scans were retrospectively reviewed by one board-certified radiologist (SM). To evaluate survival, Kaplan-Meier methods were used, with log rank Pvalues for comparisons. Results: A total of 212 eligible pts who underwent attempted primary cytoreduction followed by platinum-based systemic chemotherapy were identified for evaluation. With a median follow-up time of 52 mos, there were 135 deaths and a median overall survival of 48 mos (95% CI: 44–53). Of the 212 pts, 44 (21%) had supradiaphragmatic adenopathy with nodes >1 cm, while 168 (79%) did not have adenopathy in this distribution. None of the 44 pts with adenopathy had the enlarged nodes removed at primary cytoreduction. The median survival was 49 mos for pts with and 48 mos for patients without adenopathy (p = 0.46). In total, 155 (73%) patients underwent optimal cytoreduction (residual disease ≤ 1 cm). In the optimally cytoreduced pts, the median survival for the 125 pts without supradiaphragmatic adenopathy was 52 mos (95%CI: 45–59) compared to 51mos (95%CI: 41–58) for the 30 pts with supradiaphragmatic adenopathy (p = 0.33). Conclusions: Although a previous study has shown that supradiaphragmatic adenopathy was associated with poorer overall survival in EOC patients, our study did not confirm these findings. In our study, enlarged supradiaphragmatic nodes noted on preoperative CT scan did not have significant prognostic impact and therefore their clinical significance remains uncertain.

No significant financial relationships to disclose.
Molecular characterization of highly tumorigenic cell lines used in a xenograph model to investigate cellular therapy for the treatment of refractory ovarian cancer
Authors: Ingersoll S. B. , Yue P. , Ahmad S. , Turkson J. , Edwards J. R. , Holloway R. W.
Published: August 2020

e16516

Background: Because current therapies for ovarian cancer (OC) have little impact on the long-term survival, there is a compelling need to develop innovative strategies. Our aim was to characterize OC cell lines which can be utilized to test cellular therapy in combination with cytokines or chemotherapies to elicit a graph versus tumor response to treat refractory OC patients. Methods: SKOV-3-RFP, a red fluorescent protein (RFP) expressing line, was passaged through nude mice to create more tumorigenic lines compared to parental SKOV-3 cells. Three SKOV-3-derived lines were established and characterized for IFNα-2b sensitivity, E-cadherinand CCN1gene expression, and STAT3 activation. The cells were grown in the presence of IFNα-2b to determine proliferative effects. Tumors were harvested when mice became moribund; ascitic fluid (AF) and solid tumor (ST) tissue were snap-frozen. Expression of E-cadherinand CCN1, which have been implicated to play role(s) in OC pathobiology, were analyzed in ST harvested from the mice and from SKOV3-derived lines (SKOV3-RFP, AF1, AF2, and AF3). We investigated the activation status in the SKOV3-derived cells of STAT3, which has been associated with malignant transformation and tumor progression. Results: Parental SKOV3-RFP cells when injected at a dose of 5x106 gave a tumor incidence of 4/6 in 14 weeks. AF1 and AF2, when injected at a dose of 1x106 resulted in 100% tumor incidence in 5-weeks (n = 5). These two lines were also more resistant to IFNα-2b compared to RFP. All SKOV3-derived lines and ST expressed E-cadherin by RT-PCR. None of the SKOV3-derived lines expressed CCN1; however, one of the two AF1 ST tested expressed CCN1. Both AF2 ST evaluated showed weak expression of CCN1. In vitro DNA-binding with electrophoretic mobility shift assay (EMSA), showed AF1 and AF3 cells harbor constitutively-active STAT3, whereas the RFP line does not. Conclusions: The SKOV3-derived lines that we developed will be a better model to test novel OC treatment regiments because these lines exhibit increased resistance to IFNα-2b, are more tumorigenic in a xenograph model, show aberrant STAT3 activation, and tumors harvested from these lines express genes that make these lines more aggressive.

No significant financial relationships to disclose.
Neoadjuvant transarterial chemoembolization (TACE) using cisplatin with the combination of dose-dense intravenous administration of paclitaxel for the locally advanced cervical adenocarcinoma
Authors: Tsubamoto H. , Wada R. , Kanazawa R. , Komori S. , Maeda H. , Hirota S. , Adachi S.
Published: August 2020

e16518

Background: Adenocarcinoma (including adenosquamous carcinoma) of the uterine cervix has a tendency to early lymph node metastasis and is resistant to radiation therapy, thus results in poor prognosis compared with squamous cell carcinoma. Neoadjuvant chemotherapy (NAC) followed by radical hysterectomy (RH) for bulky cervical adenocarcinoma seems to be an alternative therapy to primary radiation. Methods: P2 at the single institution. Eligible criteria were as follows: Histologically diagnosed cervical adeno or adenosquamous carcinoma with FIGO stage IB2-IVA, Age < or equal to 75, PS 0–2, given informed consent. The NAC regimen consisted of paclitaxel (60mg/m2, iv, D1, D8, D15) and cisplatin (70 mg/m2, trans-uterine arterial infusion followed by embolization using the gelform, D2) repeated every 3 weeks for 2–3 cycles, followed by RH. Primary endpoints were clinical and pathological responses, and secondary endpoints were toxicities, relapse free survival (RFS) and overall survival (OS). Results: Enrolled patients: 22 (1998–2006), Age: median 51 (33–75), FIGO stage: IB2 (9), IIA-IIB (8), IIIB (3), IVA (2), adeno/adenosquamous: 16/6. Toxicities during NAC (CTCAE ver.3) were as follows: G3/G4 neutropenia 18% (4/22), G3/G4 anemia 14% (3/22), G3/G4 thrombocytopenia 0%, G2/G3 sensory neuropathy 0 %, G3/G4 creatinine elevation 0%, G2 alopecia 100%. Clinical response rate (RR: CR+PR) of the patients with stage IB2-IIB was 100%. 16 of 17 received RH, and no residual malignant cells were found pathologically (pCR) in 3. RR of the patients with stage IIIb-IVa was 80%, three patients completed RH with either modified anterior or posterior exenteration, and pCR was found in one patient. The rate of radiation therapy following either NAC or surgery among enrolled patients were 18% (3/17) with stage IB2-IIB and 40% (2/5) with IIIB-IVA. 5 year RFS/OS were 69%/68% with stage IB2-IIb and 60%/60% with stage IIIb-IVa. All 15 alive patients had RH. One patient with stage IVa had urostomy, and other 14 patients have no trouble in urination function. Conclusions: TACE with cisplatin and dose dense paclitaxel in the neoadjuvant setting is feasible and effective for cervical adenocarcinoma.

[Table: see text]
The relevance of rising CA-125 levels within the normal range in predicting recurrence in patients with advanced stage ovarian cancer: A validation study
Authors: AbuShain F. , Escobar P. , Shahabi S. , Michener C. , Drake R. , Rose P. G. , Schwartz P. E.
Published: August 2020

e16521

Background: Small published series suggested that three progressively rising CA-125 values, doubling of CA-125, and an absolute rise of 5 U/mL from the nadir, all while remaining in the normal range were highly associated with disease recurrence. This study aims to validate these proposed criteria in a larger population. Methods: We conducted a retrospective review of the records of patients with stages IIIC and IV epithelial ovarian cancer treated with primary surgery and adjuvant chemotherapy between 1994 and 2006. Only patients who had a complete response to chemotherapy verified by normal CT scan, CA-125 and physical examination were included. Nadir CA-125 level was defined as the first CA-125 measurement after completing chemotherapy. Available CA-125 values from diagnosis to recurrence or to last follow up were collected and evaluated for meeting any of the criteria above. Results: 91 patients with a median age of 59 (42 - 88) met the inclusion criteria. 82 patients had stage IIIC (90%) and 9 patients (10%) had stage IV. 86 patients (94.5%) had papillary serous histology and 88 patients had grade 3 (96.7%) disease. Median follow up was 43.7 months (12.6 - 156). Table 1 shows the number of patients who met any of the above CA-125 criteria in total and divided by the presence or absence of recurrence. There was no statistically significant difference in meeting any of the CA-125 criteria between the recurrence and no recurrence groups. Meeting at least one of the CA-125 criteria had 50% sensitivity, 65% specificity, and 86% positive predictive value for recurrence. The median time to recurrence in patients who met at least one CA-125 criteria was 3.8 months (0.2 - 12.4) and the median follow up time after meeting one of the CA 125 criteria in patients who did not recur was 88.5 months (10.4 - 188) Conclusions: Rising CA-125 levels within the normal range that meet any of the above criteria are highly predictive (86%) of recurrence within 12 months and closer observation is warranted. [Table: see text]

No significant financial relationships to disclose.
Dysgerminoma of the ovary 35 years on: A single institutional experience
Authors: Vicus D. , Beiner M. , Klachook S. , Le L. , Ginsburg O. , Laframboise S. , Mackay H.
Published: August 2020

e16523

Background: Ovarian dysgerminomas are rare but are relatively more common in women under 20 years of age in whom fertility is likely to be an issue. The aim of this study was to review our institutional experience in treating patients (pts) diagnosed with pure dysgerminoma. Methods: We performed a retrospective chart review of all pts diagnosed with ovarian dysgerminoma at the Princess Margaret Hospital, Toronto, between 1970 and 2005. Results: 65 pts were diagnosed with ovarian dysgerminoma, median age 21.9 years (range 8.1–64.1 yrs). 40 pts (62.5%) presented with FIGO stage IA disease; 3 (4.7%) stage IB; 6 (9.4%) stage IC; 2 (3.1%) stage II; and 13 (20.3%) at stage III, 1 unknown. Initial management was surgical for all pts: unilateral oopherectomy 47 pts (72.2%), 14 (21.5%) bilateral oophorectomy ± hysterectomy (12 pts), 3 (4.6%) cystectomy alone. 17 pts received chemotherapy, 15 adjuvant and 2 for residual disease (all post 1988); 8 for stage I, 1 for stage II, and 8 for stage III. 12 pts received etoposide and cisplatin (EP); 4 bleomycin, etoposide, and cisplatin (BEP); and 1 vincristine and cisplatin. 20 pts received adjuvant radiotherapy (all prior to 1985); 14 stage I; 1 stage II; and 5 stage III. 1 pt received a combination of adjuvant chemotherapy and radiation. 6 (9.2%) pts recurred all within 19 months of initial diagnosis. 5 of the 6 pts that recurred had stage IA disease treated with a unilateral oophorectomy, 1 received adjuvant EP. 1 pt with stage IIIC disease recurred following bilateral oophorectomy + hysterectomy and radiotherapy. Treatment of recurrent disease was by salvage surgery and chemotherapy (3 pts), radiotherapy (2 pts), and EP (1 pt). All pts who recurred responded to treatment and were alive at last follow up, median follow up 22.5 yrs (range 9.3–31.4 yrs). Median follow up, all pts, was 10.5 yrs (range 1.1 to 31.9 yrs). 15 pts attempted to conceive posttreatment; 6 had received adjuvant treatment; 4 EP; and 2 whole abdominal radiotherapy. 13 successful pregnancies and 13 live births were reported in 9 women (3 had received adjuvant EP). Conclusions: The long-term outcome of patients with an ovarian dysgerminoma is excellent. Recurrences occured within 2 years of diagnosis and are treatable. Patients can be treated with fertility sparing surgery and can expect good reproductive outcomes.

No significant financial relationships to disclose.
Chemoradiation in locally advanced cervical carcinoma: An analysis of cisplatin administration and other clinical prognostic factors
Authors: Nugent E. , Case A. S. , Zighelboim I. , DeWitt L. , Thaker P. H. , Massad L. S. , Powell M. A. , Mutch D. G. , Trinkhaus K. , Rader J. S.
Published: August 2020

e16525

Background: The standard treatment for locally advanced cervical cancer is combination weekly cisplatin and radiotherapy (RT). Toxicity and compliance issues often result in failure to complete the recommended six cycles of weekly chemotherapy. Our objective was to retrospectively evaluate the effect of number of chemotherapy cycles and other clinical and pathologic factors on progression-free (PFS) and overall survival (OS). Methods: Between January 2004 and May 2007 we identified 118 patients at our institution with locally advanced cervical cancer (stage 1B2-IVA) treated with combined weekly cisplatin (40 mg/m2) and RT from chemotherapy log records. PFS and OS were evaluated for associations with number of chemotherapy cycles as well as other clinical and pathologic factors. Kaplan-Meier and Cox proportional hazard models were utilized for statistical analyses. Results: The median age and BMI were 51 years (25–86) and 29.2 kg/m2 (15–69). The majority of patients had stage IB2 or II disease (70%), squamous histology (91%), and size <6 cm (65%). Median RT duration was 50 days and 95% received brachytherapy. 30% of patients completed fewer than 6 cycles of chemotherapy and estimated PFS and OS were 63% and 75% respectively. 32 recurrences were detected with a median time to progression of 27 months. In multivariate analyses, number of chemotherapy cycles was independently predictive of PFS and OS. Patients that received <6 cycles of cisplatin had a worse PFS (HR 2.65; 95%CI 1.35–5.17; p = 0.0045) and OS (HR 4.47; 95% CI 1.83–10.9; p = 0.001). Additionally, advanced stage, longer time to RT completion, and absence of brachytherapy were associated with decreased OS and PFS (p < 0.05). Higher grade was associated with decreased PFS (p = 0.03) but not OS. Age, race, BMI, tumor size, smoking, histology, and IMRT were not statistically significant for OS or PFS. Conclusions: Number of cisplatin cycles, stage, grade, time to radiotherapy completion, and brachytherapy, are prognostic of PFS and OS in patients with cervical cancer undergoing treatment with combined cisplatin and RT. Efforts to decrease toxicity and improve compliance allowing for completion of six cycles of cisplatin may be associated with increased progression free and overall survival.

No significant financial relationships to disclose.
Prognostic significance of obesity in high-grade serous carcinoma of the ovary
Authors: Schlumbrecht M. , Urbauer D. , Gershenson D. , Broaddus R.
Published: August 2020

e16528

Background: Obesity is an epidemic public health problem in the United States. In gynecologic oncology, obesity is an established risk factor for endometrial cancer. However, its role in the pathogenesis and survival in ovarian cancer is debated. Recent studies have attempted to elucidate a possible relationship, but variations in design and heterogeneity in patient characteristics make it difficult to draw definitive conclusions. The purpose of our study was to determine if body mass index at the time of treatment initiation for high grade serous ovarian carcinoma has an effect on patient outcome. Methods: Nine-hundred four patients treated for ovarian cancer at M.D. Anderson Cancer Center were identified between 2002 and 2007. Patients were excluded for low grade or non-serous histology, neoadjuvant treatment, or if presenting with recurrent disease. Clinicopathologic data were extracted by retrospective chart review. Patients were stratified by body mass index (BMI) as normal (BMI<25), overweight (BMI 25-<30), or obese (BMI>30). All were treated with primary cytoreduction and standard platinum/taxane chemotherapy. Chemotherapy was dosed using adjusted body weights. Outcomes included time to recurrence, overall survival, success of surgical debulking, and chemotherapeutic toxicities. Statistical analysis was performed using Fisher's exact test, Wilcoxon test, and Kaplan-Meier estimates. Results: A total of 127 patients were included for analysis. Patients were followed for a mean of 37 months (range 3–86 months). Twenty-one patients were obese (16.5%), and 35 were overweight (27.5%). Diabetes was more prevalent in the obese cohort (p = 0.0038). There was a trend towards greater likelihood of suboptimal debulking in obese patients, but this did not reach statistical significance (p = 0.06). BMI had no effect on recurrence-free survival (HR 0.69 [CI 0.39–1.23], p = 0.21) or overall survival (HR 0.95 [CI 0.68–2.43], p = 0.91). There was no difference in chemotherapy side effects or chemoresistance across BMI strata. Conclusions: Body mass index has no effect on survival in women with high grade serous ovarian cancer. Effectively managing comorbidities and ensuring adequate chemotherapy dosing in the obese patient is crucial for optimizing outcome.

No significant financial relationships to disclose.
Sequential or combination therapy in the management of recurrent ovarian carcinoma: Clinical experience beyond clinical trials
Authors: Gueth U. , Wight E.
Published: August 2020

e16530

Background: There is a vast amount of literature on the effect of systemic therapy in patients with recurrent ovarian carcinoma (ROC) enrolled in clinical trials. However, there are only a few reports that focus on the treatment during the entire course of disease and its changes and development over time. Methods: We investigated the entire treatment course (all agents administered, number of treatment lines, cumulative time of therapy in relation to survival time) in a population-based cohort of 133 ROC patients. In study group A (n = 63), ROC was diagnosed between 1998 to 2006; in group B, ROC was diagnosed between 1990 to 1997 (n = 70). Results: 7.9% of the patients in group A and 8.6% in group B did not receive any chemotherapy in the palliative setting. Comparison between sub-study groups A and B showed similar overall survival (recurrent disease-specific survival): 19 months (A) vs. 18 months (B); p = 0.549. Compared to group B, the patients in the more recent subgroup A received significantly fewer combination therapies (12% vs. 24.1%, p = 0.0057) but more therapy lines (≥3 lines in 56.1% vs. 31.1%, p = 0.005) and also had significantly longer times of treatment in relation to survival time (mean ratio 57.5% vs. 47.5%, p = 0.014). The distribution of the main agents administered in the course of disease was as follows (A vs. B): carboplatin 31.0% vs. 34.7%; pegylated liposomal doxorubicin (PLD): 19.7% vs. 2.0%; gemcitabine 19.2% vs. 3.0%; paclitaxel: 10.7% vs. 14.6%; topotecan: 9.1% vs. 2.5%; others: 10.3% vs. 43.2%. Conclusions: In the current study group, a similar outcome could be achieved with less aggressive treatment regimens, i.e. with fewer combination therapies and with longer treatment periods. Currently, in a palliative treatment setting, the primary goals of surveillance of ROC patients are maintenance and/or an enhancement of quality of life, which can be achieved using less toxic agents such as gemcitabine and PLD.

No significant financial relationships to disclose.
The predictive and prognostic value of serum CA 125 kinetics and CA 125 nadir during paclitaxel/platinum based chemotherapy in patients with advanced ovarian carcinoma
Authors: Tibau A. , Ojeda B. , Nadal R. , Pérez Altozano J. , Boguña I. , Artigas V. , Gallardo A. , Pérez C. , Lopez J. , Barnadas A.
Published: August 2020

e16534

Background: The tumor marker CA 125 is an accurate and reliable marker for monitoring the response to treatment and detecting early relapse in epithelial ovarian cancer (EOC). The aim of this retrospective study is to analyze the predictive and prognostic value of CA 125 kinetics and the implications of the different levels of CA 125 within the normal range after chemotherapy (CT). Methods: Between 1996 and 2008, 127 patients (pts) were treated with standard CT regimen for FIGO stage IIb-IV EOC. Median age was 64 years (24–87). Tumors were classified: 70 (55%) serous, 24 (19%) poorly differentiated, 14 (11%) endometrioid and 19 (15%) clear cell carcinoma. FIGO stage: 12 (9%) II; 95 (75%) III; and 20 (16%) IV. Tumor grade: 1 (1%) G1; 11 (9%) G2; and 115 (90%) G3. Residual disease after initial surgery: 52 (41%) optimal <2cm and 39 (31%) suboptimal. After surgery, 117 (92%) of the pts received a median of 6 cycles/patient with platinum based (cisplatin or carboplatin) CT in combination with paclitaxel. Median follow-up was 31 months. 93 (73%) pts achieved levels <35 U/ml after CT. Survival analyses for disease-free survival (DFS) and overall survival (OS) used univariate (Kaplan-Meier) and multivariate (Cox) model. Results: For 127 stage IIb-IV pts, 88 (69%) relapsed and 60 (47%) died from EOC. The median DFS for 3 groups 1, 2 and 3, was 34, 20, 14 months, respectively (p < 0.0001). The median OS for 3 groups was 7.5, 3 and 3 years, respectively (p < 0.0001). Pre-CT Ca 125 (p < 0.002), and time to negativization (p < 0.043) all had a univariate prognostic value for DFS and OS. In Cox models, FIGO stage (p < 0.0001) and nadir concentration (p < 0.0001) were the most powerful prognostic factors for DFS and OS. We found no differences in DFS and OS related to time to nadir. Conclusions: Serum CA 125 kinetics during early CT has a strong predictive and prognostic relevance for patients with advanced EOC. Within normal range, the differences between CA 125 levels could add prognostic information, stratify pts according to the risk of progression and would be a useful tool when performing consolidation CT in future clinical trials.

No significant financial relationships to disclose.
Pegylated liposomal doxorubicin in recurrent serous carcinoma of the uterus
Authors: Dizon D. S. , Stuckey A. , Schwartz J.
Published: August 2020

e16538

Background: Serous carcinoma of the uterus behaves in a much more aggressive fashion than endometrioid tumors of the uterus with risks almost equivalent to ovarian cancers. Given this, we were interested in seeing if pegylated liposomal doxorubicin had a differential benefit in serous cancers of the uterus when compared to endometrioid carcinomas. Methods: Patients with recurrent serous and endometrioid uterine cancer treated with pegylated liposomal doxorubicin between 1999 and 2007 were identified. Demographics, stage, grade, and prior lines of chemotherapy were collected. The primary objectives were to determine progression-free (PFS) and overall survivals (OS) in these subsets of women with recurrent endometrial cancer. Results: Twenty-three patients with recurrent serous histology and 24 with endometrioid histology were identified. The median age at diagnosis in the serous group was 70 (45–89) and 62 (37–94) in the endometrioid cohort. The majority of patients in both groups were Caucasian. There was no difference between the serous and endometrioid cohorts by stage with advanced disease in 65% and 73%, respectively (p = 0.95). The majority of patients had 2 prior lines of treatment. The most common prior chemotherapy was carboplatin and paclitaxel. The median number of pegylated liposomal doxorubicin cycles was 4 in both groups. The median PFS was 4.6 months in the serous cohort and 4.7 months in the endometrioid group (p = 0.47). The median overall survival in the serous group was 9.8 months and in the endometrioid group it was 9.6 months (p > 0.5). Conclusions: We did not find a difference in survival endpoints in women with serous versus endometrioid histologies. While pegylated liposomal doxorubicin appears to be equally active in these groups, survival is uniformly poor in the context of recurrent disease.

No significant financial relationships to disclose.
Role of an EpCAM auto-antibody in ovarian cancer patients with special regard to disseminated tumor cells in bone marrow
Authors: Heubner M. , Kasimir-Bauer S. , Errico D. , Herlyn D. , Kimmig R. , Wimberger P.
Published: August 2020

e16557

Background: EpCAM is a tumor associated antigen which is frequently expressed in ovarian cancer. Recently, an autoantibody (AAB) against EpCAM has been identified in ovarian cancer patients. Autoantibodies are immunogene factors and might be of prognostic importance. We showed that disseminated tumor cells (DTC) in bone marrow carry the EpCAM antigen on their surface and correlate with poorer progression free survival (PFS). Here, we evaluated whether EpCAM-AABs have an impact on clinical parameters or the presence of DTC in ovarian cancer patients. Methods: EpCAM-AABs were determined in sera of 28 healthy voluntary age matched females and 62 patients with primary epithelial ovarian cancer before and after platinum-based chemotherapy using a recombinant EpCAM-epitope for antibody- detection by ELISA technique. Mean follow up time was 13 months. DTC in BM were detected by immunocytochemistry applying the pan cytokeratin antibody A45-B/B3. All samples exceeding the mean antibody titer of healthy controls plus 2 standard deviations were considered positive. Results: The antibody titer of healthy controls was 0.061 + 0.015. Using a cut-off value of 0.091, we found 9/62 (15%) ovarian cancer patients to be positive for EpCAM-AABs after first-line treatment. Interestingly, no positive AAB-titers were seen before therapy. Using the paired T-Test, we noted a significant posttherapeutic increase of AABs (CI 0.95, p < 0.0001). Analysis of PFS, FIGO stage, resection status, grading, age, sensitivity to platinum based chemotherapy and DTC did not reveal significant associations with positive EpCAM-AAB titers. Conclusions: The clinical course of ovarian cancer patients and the prevalence of DTC were not altered by EpCAM-AABs. Interestingly, we observed an increase of antibody-levels after first-line treatment. For further validation, we intend to extend our patient collective. In future, it might also be interesting to investigate the impact of AABs on response to targeted therapies against EpCAM.

No significant financial relationships to disclose.
Impact of malnutrition on surgical outcome of patients with ovarian cancer: Results of a prospective study
Authors: Skowronek P. , Kuhberg M. , Chen F. , Schwarz J. , Lichtenegger W. , Sehouli J.
Published: August 2020

e16564

Background: The purpose of this study was to examine an influence of poor nutritional status on surgical outcome in patients with ovarian cancer. Methods: Data from 152 consecutive patients with histologically confirmed ovarian cancer were prospectively analyzed. Overall 79 suffered from primary and 73 from recurrent disease. All patients received a systematic nutritional assessment prior to cytoreductive surgery and postoperative all complications were analyzed in detail. The Nutritional Risk Score (NRS-2002) was used to identify patients at high nutritional risk (NRS≥3). Intraoperatively, a standardized documentation script (IMO) was applied including tumor localization, surgical interventions, and postoperative residual tumor mass. Results: 29 patients (19%) were classified as malnourished, including 19 (24%) with primary and 10 (14%) with recurrent disease. These patients showed a significantly poorer performance status preoperatively compared to patients with NRS<3 (p < 0.05), which was assessed according to the American Society of Anesthesiologists (ASA). Also an intra-operatively documented tumor spread was significantly more extended in group with NRS≥3 than among patients with NRS<3 (p < 0.05). In malnourished patients complete resection rate was significantly decreased (31% vs. 69%, p < 0.001) and they required more often a colo- or ileostoma (17% vs. 6%, p = 0.041). Malnourished patients suffered more often from post-operative complications (62% vs. 37%, p < 0.05), especially infectious like pneumonia or sepsis. All postoperative mortality events (3 cases) occurred in the malnourished group. Conclusions: Malnourished ovarian cancer patients have significantly more often post-operative complications. They suffer from more extended tumor spread and were less frequently postoperatively tumor-free. Based on our results further prospective trials of preoperative nutritional therapy to improve surgical outcome are warranted.

No significant financial relationships to disclose.
A second peritoneal cytology instead of the initial cytology as a prognostic factor in epithelial ovarian cancer
Authors: Sirop S. , Saha S. , Soni M. , Chkravarty B. , Korant A. , Dutt N. , Wilson D. , Ng P. , Arora M. , Singh T.
Published: August 2020

e16572

Background: Ovarian cancer (OvCa) is the most common gynecological malignancy causing death. Positive (+ve) peritoneal cytology is an important prognostic factor. The role of a repeat peritoneal washing after resection of the tumor at the time of surgery has not been evaluated in the past. Methods: A retrospective analysis of our prospective cohort database was undertaken. Patients (pts) diagnosed with OvCa between 2001–2007 were included in the study. All pts underwent debulking surgery with two peritoneal washings during surgery: one before and one after resection of the tumor. The primary outcome was overall survival. Exclusion criteria included second malignancy, refusal of chemotherapy, or non-surgical candidates. Only stage III andIV pts were included in the follow-up analysis. Results: Forty three pts were included in our study. Of these, 8 (gp A) had both peritoneal washings +ve for malignancy, 16 (gp B) had the first washing +ve and the second one negative (-ve) for malignancy, and 19 (gp C) had both washings -ve for malignancy. There was no significant difference in the demographics and grade of disease (Table). There was more serous histology in gp B as compared to gp A and gp C. The median length of stay was 13.2, 10.9, 9 days and the median CA 125 level at the time of diagnosis was 651, 440 and 445 in gp A, B and C respectively. Bowel was involved and required radical resection in 75%, 41.7%, and 26.3% in gp A, B, and C, however the rates of optimal cytoreduction were 75%, 84.6% and 90.9% respectively. The minimum follow-up was 12 months. The percentage of pts with persistent or recurrent disease was 62.5%, 41.7%, and 36.4% in gpA, B and C respectively. There was improved survival in gp C as compared to gp B and gp A. (42 months vs 23.5 months vs 13 months respectively). Conclusions: While preliminary, our study shows that at the time of debulking surgery of OvCa, a -ve peritoneal washing after resection of the tumor following an initial +ve washing is a possible independent prognostic factor. [Table: see text]

No significant financial relationships to disclose.
Low-dose methotrexate and cyclophosphamide in recurrent ovarian cancer
Authors: Scheusan R. , Curescu S. , Stanculeanu D. , Curescu P.
Published: August 2020

e16574

Background: Ovarian cancer continues to be the leading cause of death secondary to gynecologic cancers among women. Despite the fact that new chemotherapeutic drugs have been found effective, the prognosis of these women continues to be poor. Metronomic chemotherapy, chronic administration of chemotherapy at relatively low, minimally toxic doses on a frequent schedule with no prolonged drug-free breaks, is a potentially novel approach to the control of advanced cancer disease. It is thought to work primarily through antiangiogenic mechanisms and has, as an advantage, the property of significantly reducing toxic side-effects. Purpose: to evaluate the efficacy and toxicity of metronomic chemotherapy using low dose methotrexate and cyclophosphamide in patients with refractory pretreated ovarian cancer. Methods: From May 2007 to July 2008, 11 patients with refractory pretreated ovarian adenocarcinoma were included. Patient's characteristics: median age 51 years (range 41–64), ECOG 0–2, progression after more than two lines of chemotherapy for recurrent disease. Treatment: low-dose oral methotrexate 2.5 mg bd on days 1 and 2 each week and cyclophosphamide 50 mg/day administered continuously until disease progression. Follow-up: every month clinical examination, ECOG, blood test; every two months CA-125; every four months CT-scan. Results: All patients were evaluable for response and toxicity. There was no complete response; 2 pts (18.18%) - partial response and the overall clinical benefit rate was 54.54%. The median time to progression was 4.4 month. Main toxicities according to WHO criteria were: grade 1–2 gastrointestinal toxicities (nausea, vomiting) 4 pts (36.36%), grade 1–2 anemia 4 pts (36.36%), grade 1–2 neutropenia 2 pts (18.18%). No grade 3–4 toxicities was observed. Conclusions: Metronomic metotrexate-cyclophosphamide is minimally toxic and effective in heavily pretreated recurrent ovarian cancer. In conclusion, metronomic regimen could represent a potentially significant palliative treatment for these patients. A better understanding of mechanism of actions would help determine the optimal dose and schedule for metronomic chemotherapy regimens as antiangiogenic therapy.

No significant financial relationships to disclose.
Surgical and immunohistochemical (IC) risk factors for metastatic disease in stage IB1 cervical cancer (CC)
Authors: De La Mota J. , Thomas B. , Fengwei W. , Micaily B. , Yajue H. , Hernandez E.
Published: August 2020

e16578

Background: Stage IB1 CC is treated with radical abdominal hysterectomy (RH) and pelvic lymph node dissection (LND) because of presumed risk of parametrial and nodal involvement. We sought to identify surgical and IC risk factors for metastatic disease. Methods: Retrospective chart review of all stage IB1 CC patients who underwent RH and LND from 1996–2008. Results: Of the 35 patients identified, 25 (71%) had squamous cell, 9 (26%) adenocarcinoma, and 1 (3%) adenosquamous histology. Median tumor diameter of patients without lymphovascular space involvement (LVI), with LVI, and with positive LN was 1.2, 2.0, and 2.5 cm respectively. Median of 24 LNs was removed. LVI was noted in 13 (37%) patients of whom 5 (38%) had positive LN. None of the 22 patients without LVI had LN involvement. Only 2 of 35 (6%) had parametrial involvement, both of which had positive LN. All patients with positive LN received chemo-radiation. In addition six patients with LVI and deep cervical stromal invasion received adjuvant radiation therapy. Median follow-up was 14 months. Postoperatively 8 (23%) and 4 (11%) patients had early and late complications respectively. There was one (3%) vaginal recurrence in a patient with positive LN. The 5-year progression-free survival and overall survival was 95% and 100%, respectively. Immunohistochemical (IC) staining was performed on 29 cases (10 LVI, 4 positive LN) for bcl-2, p53, Ki-67. There was increased staining for Ki-67 in patients with LVI (61% vs. 44%, p = 0.01), and in those with positive LN (66% vs. 48%, p = 0.04). No correlation was found with p53 or Bcl-2. Conclusions: The rate of LN metastasis in patients with stage IB1 CC is significant (14 %), as is the rate of parametrial involvement (6%). However, it occurred only in patients with LVI. Staining for Ki-67 may help detect high-risk patient. RH followed by adjuvant therapy in high-risk patients resulted in 100% 5-year survival, but is associated with morbidity.

No significant financial relationships to disclose.
YKL-40 and CA 125 serum levels in patients with ovarian cancer
Authors: Chudecka-Glaz A. , Zielinska D. , Rzepka-Górska I.
Published: August 2020

e16579

Background: CA 125 is known and useful marker in diagnosis and follow up of patients with ovarian cancer. But there is only a few study about YKL-40 and its usefulness in these patients. The aim of our study was to compare the serum levels of YKL-40 and CA 125 in patients with active phase of ovarian cancer disease (during diagnosis and recurrence). Methods: We analyzed 58 women with ovarian cancer hospitalized and treatment in period from January 2006 to March 2008. Group I - 42 patients constituted women with actually diagnosed ovarian cancer and group II women with recurrence of ovarian cancer. Results: Mean value of YKL-40 in patients with just diagnosed ovarian cancer was 181 ng/mL (16.42–766.1 ng/ml). Mean value of YKL-40 in patients with the recurrent of ovarian cancer was 122.38 ng/mL (9.47–389.22 ng/mL). CA 125 respectively 729.58 U/mL (10.62–4882.1 U/mL) and 579.15 /mL (5.38–6000 U/mL). When the cut-off level for YKL-40 was set at 130 ng/mL we found elevated serum levels in 50% of group I and 38% of group II. Respectively in group I we found 73% elevated values of YKL-40 and 44% in group II when the cut-off level was set at 61 ng/mL. In patients with diagnosed ovarian cancer percentage of elevated CA 125 serum value was 90% and 55% in recurrent ovarian cancer (cut-off level -35 U/mL). Conclusions: Significance of YKL-40 tumor marker in ovarian cancer diagnosis seems to be less then known CA 125 antigen.

No significant financial relationships to disclose.
Primary squamous cell carcinoma of the oral cavity at presentation in Pakistan
Authors: Jamshed A. , Hussain R. , Rehman K. , Iqbal H. , Hameed S. , Majeed U. , Shah M. A. , Azhar R. , Ahmed Q. , Faruqui Z.
Published: August 2020

e17002

Background: Squamous cell carcinoma of oral cavity (SCCOC) is characterized by marked geographical differences in frequency and site distribution. Pakistan is situated within the high risk zone on the global oral cancer map. However, no reliable data exists on oral cancer in this area. Our aim was to determine clinicopathological features and patterns at presentation of primary SCCOC in a comprehensive cancer centre in Pakistan. Methods: Demographic, risk factors, pathological and AJCC staging data for SCCOC treated at Shaukat Khanum Memorial Hospital for the period November 2003-October 2008 were obtained from the head and neck unit database. Results: The database identified 666 patients with biopsy proven primary SCCOC. Mean age was 53 years (range 12 - 90 years). Male (428): Female (238) ratio was M64%:F36%. The occurrence of major risk factors for oral cancer specifically smoking, betel quid chewing, naswar (smokeless tobacco) and alcohol use in males (428) was 45% (193), 28% (118), 29% (126), 3% (13), and in females (238) was 8% (20), 29% (68), 13% (30), 0% (0), respectively. Thirty-eight percent (411/666) had no association with tobacco, betel quid or alcohol use. Subsite within oral cavity; anterior tongue 41.1% (274), buccal mucosa 26.6% (177), lower gingival and alveolus 19.5% (130), upper gingival and alveolus 4.1% (27), lips 3.6% (24), retromolar trigone 2.9% (19), hard palate 1.7% (11), and floor mouth 0.6 (4). Broder's/World Health Organization histological grade; grade I 52% (334), grade II 34% (226), grade III 7% (49), and unknown 5% (36). According to AJCC 2002 system 0.2% (1), 10.8% (72), 12.2% (81), 13.2% (88), and 63.7% (420) had stage 0, I, II, III, and IV, respectively. Conclusions: Approximately 80% of patients with primary SCCOC present with stage III or IV disease with anterior tongue as the most common subsite in our hospital. While tobacco and betel quid chewing can be attributed to development of SCCOC in a significant proportion of patients, nearly 38% are unlinked to typical risks factors suggesting other environmental and genetic agents as etiological factors in this region.

No significant financial relationships to disclose.
Alternative therapeutic approaches after induction chemotherapy for tonsil squamous cell carcinomas
Authors: Huguet F. , Gratacap M. , Ménard J. , Perie S. , Angelard B. , Jafari A. , Pène F. , Torti F. , Touboul E. , Lacau St Guily J.
Published: August 2020

e17010

Background: The role of induction chemotherapy (ICT) in the treatment of head and neck squamous cell carcinomas (SCC) remains controversial. This retrospective study aims to evaluate the outcome of patients with tonsil SCC treated with ICT followed by surgery and/or external beam radiotherapy (EBRT). Methods: Between 1997 and 2007, 103 patients (pts) with tonsil SCC received an ICT in Tenon Hospital. Most of pts (88%) received cisplatin (25 mg/m2) and 5-fluorouracil (1,000 mg/m2) for 4 days with a mean of 2.5 cycles. After ICT, 85 pts were operated. After surgery, 69 pts received a dose of 50 to 70 Gy on the primary site depending on pathological findings (Group 1). Sixteen pts with negative margins and no lymph node metastasis didn't receive any EBRT (Group 2). The remaining 17 pts were treated by EBRT without surgery (Group 3). The mean follow-up was 38 months. Results: No significant difference appears between our different groups except for the TNM stage and the tumour pathological response to ICT. After ICT, pathological complete response was observed in 18 pts (25%) for the primary site and 20 pts (34%) for lymph nodes. Clinical and radiological assessment of response after ICT was not predictive of the pathological response. The TNM stage was the only predictive factor for complete response. The 5-year disease-free survival rates were 68% for the whole population, 73% for the Group 1, 43% for the Group 2, 68% for the Group 3 (p = 0.5). A poor pathological response after ICT was the single independent predictive factor of tumour relapse (p = 0.04). In the Group 2, 6 pts had a relapse, among them 4 had EBRT in a second time. The 5-year specific survival rates were 78% for the whole population, 76% for the Group 1, 76% for the Group 2, 39% for the Group 3 (p = 0.03). The radio-clinical evaluation of response, the surgery and the pathological response were predictive factors of specific survival. Conclusions: Pts with a complete pathological response after ICT who were not irradiated had a non significant increase of the relapse rate with a specific survival identical to the group of irradiated pts. This data have to be confirmed by a prospective trial.

No significant financial relationships to disclose.
TS and MTHFR gene polymorphisms in patients (pts) with recurrent or metastatic squamous cell carcinoma of the head or neck (SCCHN) treated with pemetrexed (P) and bevacizumab (B)
Authors: Romkes M. , Feinstein T. M. , Zhong S. , Buch S. , Gibson M. K. , Skovira K. , Argiris A.
Published: August 2020

e17011

Background: P inhibits multiple enzymes in folate metabolism. We examined polymorphisms in thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) in patients with SCCHN treated in a phase II clinical trial with P and B (ASCO 2008; A6069). Methods: All pts were treated with P 500 mg/m2 and B 15 mg/kg, given IV every 21 days until progression. Primary endpoint was time to progression (TTP). DNA was isolated from whole blood samples using commercially available kits. Polymorphisms examined were MTHFR (C677T, A1298C and G1793A) and TS (TS2R3R, TSG2RG and TSmut6). The MTHFR SNPs were detected using TaqMan based SNP genotyping kits from Applied Biosystems, run on the ABI Prism 7700 Sequence Detection systems v 1.7 (Foster City, CA). The TS promoter repeat and promoter SNP polymorphisms and the 3’ untranslated region 6 bp deletion polymorphism were determined using published methods to detect PCR product size and RFLP-PCR assays respectively. Results: 22 pts were genotyped from 34 enrolled. There was no significant difference in characteristics between pts with and without genotype data. For the MTHFR polymorphism C677T, there was a trend towards decreased disease control rate (DCR) (CR/PR/SD) (p = 0.058, Jonckheere-Terpstra trend test) and worse TTP (p = 0.04) transitioning from variant CC to CT to TT; comparing TT genotype versus CT and CC combined, pts with TT had inferior DCR (p = 0.03) and TTP (p = 0.0003); homozygotes with TT had a median TTP of 2.6 months (mo) 95% CI (1.4, NA) versus 5.6 mo (4.2, 11.4) for pts with CT or CC variants. For the MTHFR A1298C SNP, there was no significant difference in DCR between variants, median TTP for homozygotes pts with AA was 4.1 mo (2.6, NA) vs. 6.7 mo (5.1, NA) in pts with AC or CC variants (p = 0.084); median overall survival for AA was 10.2 mo (7.6, NA) and for AC or CC 17.6 mo (17, NA) (p = 0.045). The MTHFR G1793A and TS polymorphisms did not impact DCR, TTP or overall survival. There was no association between any polymorphism and the incidence of grade >2 toxicities. Conclusions: Polymorphisms in MTHFR are potentially associated with antitumor efficacy of P-based therapy in recurrent or metastatic SCCHN. These results warrant validation in larger studies with P in SCCHN.

No significant financial relationships to disclose.
TPF induction therapy with radioimmunochemotherapy for the treatment of head and neck cancer
Authors: Jordan W. , Wildfang I. , Welkoborsky H. , Borghardt J. , Zakaria H. , Tschechne B.
Published: August 2020

e17021

Background: As of the good data for radiotherapy with cetuximab and the promising results of an induction chemotherapy containing docetaxel we developed a combination of these regimes. This retrospective analysis evaluates the safety and feasibility of a TPF induction therapy under pegfilgrastim protection with a subsequent concomitant RT immunochemotherapy using cetuximab. Methods: 64 patients (8 female/56 male) with advanced (mostly metastatic; T3/T4) head & neck cancer were treated. Patients were between 39 and 78 years old (median 61), ECOG between 1 and 3. Induction therapy consisted of three 21-day-cycles TPF (75 mg/m2 docetaxel d1; 35 mg/m2 cisplatin d1,2; 750 mg/m2 5-FU d1–5) and on d7 a protective dose of 6 mg pegfilgrastim. Before and after induction therapy PET-CT was used to evaluate response. PET-CT allowed best possible RT-planning with best adapted field margins. Subsequent radioimmunochemotherapy consisted of 400 mg/m2 cetuximab on day 1 (initial dose) and seven weekly cycles of 250 mg/m2 cetuximab and 40 mg/abs cisplatin on day 1. Radiotherapy on d1–5/; 1,8 Gy/day for a median dose 61,2 Gy (59,4 - 70,2 Gy). During the whole treatment CRP was monitored twice weekly and if necessary antibiotics were administered iv. Results: All 64 patients were evaluated after therapy completion. One death occured which was not treatment related (myocard infarct). Five patients decided not to complete the treatment. The response rates were: CR 56% (36), PR 31% (20), SD 11% (7), and PD 2% (1). 10 grade 3/4 toxicities had to be observed during radioimmunotherapy (skin rash, diarrhoe). All toxicities were reversible. In five patients therapy had to be interrupted for two weeks (skin rash). Karnofsky index could be kept stable and in some cases even improved. Conclusions: The new regimen is safe, shows great promise and deserves further development. PET-CT as a diagnostic tool, pegfilgrastim as a myeloprotective agent and docetaxel/cetuximab make a good combination. Especially during the induction therapy QoL is drastically improved.

No significant financial relationships to disclose.