bluuebunny/crossref_metadata_2025 huggingface dataset:
Second-line chemotherapy with cabzitaxel and prednisolone (CP) in castratation-resistant prostate cancer (CRPC): Tolerability and efficacy—A U.K. institution experience.
Authors: Montazeri Amir H , Eswarvee Chinnamani , Wong Helen , Malik Zafar I
Published: March 2020

e15128

Background: There are limited options for CRPC patients post docetaxel treatment. The majority of these patients have advanced disease with bone metastasis and often have reduced marrow reserve. Cabazitaxel is a novel taxane with activity in docetaxel-resistant/ sensitive cancers with proven clinical benefit in a phase 3 trial. Concerns have been expressed about efficacy and toxicity of this agent in a non trial population. Methods: In this retrospective case study, patients with CRPC treated with CP between Jan-Dec 2011 were included. Response rates (PSA, ALP, radiological) and toxicities (CTCAE) were recorded. All statistical analysis was performed using SPSS v18. Results: 22 men received CP with pegfilgrastim. 41% completed at least 6 cycles of CP and 23% completed 10 cycles. 27% had radiological partial response (RECIST). 36% of patients had ≥50% reduction in PSA level and 61% of patients with elevated ALP had ≥50% reduction. Median follow up was 7.9 months. Progression was defined as clinical, PSA or radiological. 3 patients discontinued treatment because of abnormal LFTs and a further 5 patients for toxicities summarised below. Conclusions: Response rates (RR) in our series (RECIST 27% & PSA 36%) compared favourably with those in the TROPIC trial (14% & 39% respectively) and support CP as an effective and well tolerated option in CRPC. An intriguing finding was the significant RR in ALP level with CP. This may reflect bone penetration of this agent and may correlate with symptom relief and improved clinical outcome. Further prospective studies are needed to investigate this marker with clinical outcome. Data for time to progression, progression free survival and overall survival is immature at this stage and will be updated for the meeting. To our knowledge this is the first case series of patients treated with CP presented outside a clinical trial. [Table: see text]
Combination of a polyamine-free oral nutritional supplement (ONS) with docetaxel in castrate-resistant prostate cancer (CRPC) patients (pts): A phase II trial.
Authors: Cipolla Bernard G , Artignan Xavier , Miglianico Laurent , Bligny Dominique , Abraham Christine , Moulinoux Jacques Philippe
Published: March 2020

e15131

Background: Polyamines (PA) are essential for cancer cell growth. Reducing exogenous PA (foods + gut flora) and blocking PA synthesis, reduces tumour growth and potentializes chemotherapy in rodent tumour models. We have developed a PA “free” ONS, which inhibits tumour growth by 40% in pre-clinical models and assessed its tolerance with docetaxel in CRPC pts. Methods: 30 pts, 71 ± 7 years, with metastatic CRPC, median PSA: 95 ng/ml, were assessed for tolerance, quality of life (QOL) (QLQ C-30 questionnaire), W.H.O. performance status (P.S.), pain scores and prostate specific antigen (PSA) response. 90% pts were painful. 75% pts had opiate or morphinic analgesics at day 0 (D0). Median pain score is 5 (0 to 10 scale). The PA free ONS was given as sole diet (6 cans a day) for 14 days then progressively reduced and given with low PA containing foods. Docetaxel administration started on day 21 for 6, 75 mg/m2 injections, every three weeks with prednisone. Nutrialys Medical Nutrition, France, provided the PA free ONS. Results: 27 pts were evaluated for the PA ONS free phase. 18 pts completed the trial at scheduled dates and docetaxel doses. 9 pts did not complete the trial: disease progression (n=4), initial thrombocytemia (n=2), 2 deaths and 1 GI intolerance PA free ONS stage: No specific toxicity. QOL (p=0,04), pain (p=0,03) and anorexia (p=0,01) are improved at day 14. 1 pt had a > 50 % PSA decrease. PA free ONS + docetaxel stage: grade 1 or 2 nausea, vomiting or diarrhoea in < 35 % pts, 12% grade 1 neuropathy, no onycholysis or skin toxicity. Body weight and biological parameters are preserved except for two grade 4 neutropenias. P.S., Q.O.L. and pain scores and anorexia are improved. 55% pts cut their analgesics by ≥ 30% WITH stable or improved pain score. 13 pts (70% pts who completed the trial) had an > 50% PSA decrease with an 8 weeks median response time. Conclusions: A PA free ONS exclusive diet is well tolerated with significant QOL and pain improvements. The docetaxel PA free ONS combination tolerance is excellent with improved P.S., pain score and analgesic reduction. AE during chemotherapy are minimal. PSA responses are observed in a significant proportion of treated patients.
Vitamin D status and skeletal health in black men starting androgen deprivation therapy for prostate cancer.
Authors: Gunnarsson Orvar , Basaria Shehzad , Gignac Gretchen
Published: March 2020

e15139

Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with increased incidence of osteoporosis and fractures. However, much of this information is in Caucasian men. Our aim was to evaluate the prevalence low 25-hydroxyvitamin-D levels and low bone mass in black men starting ADT. Methods: A chart-based retrospective review was conducted on all patients diagnosed with PCa and were deemed appropriate to start ADT in a tertiary care center between September 2007 and July 2010. Baseline data were collected on vitamin-D status and bone mineral density (BMD). Vitamin-D sufficiency was defined as levels ≥30 ng/ml, insufficiency as <30ng/ml and deficiency as ≤20ng/ml. Osteopenia was defined when T scores were between -1 to -2.5 and osteoporosis when T scores ≤ -2.5. Results: A total of 113 black men had evaluable data (mean age 68.9±9.0; range 45-92). At baseline, mean vitamin-D levels were 20.8±9.0 ng/ml (range 4.0-43.0), lumbar Spine T-score was -0.37±1.46 (range -4.20-3.34;) and femoral neck T-score was -0.94±1.04 (range -3.00-1.50). A total of 49.4% of our patients were vitamin-D deficient (13.5±4.6), 33.7% had insufficiency (24.5±3.1) and 16.9% had sufficient vitamin-D levels ( 34.7±4.3). 59.3% of patients had normal BMD, 31.5% had osteopenia and 9.3% had osteoporosis. Conclusions: A significant proportion of black men starting ADT have low Vitamin-D levels and low bone mass. These observations should be taken into account when starting ADT in black men.
Safety data of cabazitaxel in patients treated for metastatic castration-resistant prostate cancer after docetaxel treatment: Results of a cohort of patients during the temporary authorization for use in France (ATU).
Authors: Houede Nadine , Eymard Jean-Christophe , Tahar Zoubir
Published: March 2020

e15142

Background: The TROPIC (Johann Sebastien de Bono et al ; Lancet 2010) study demonstrated that cabazitaxel (a novel tubulin-binding taxane drug) improves overall survival of patients (pts) with mCRPC who progressed during or after docetaxel-based chemotherapy, with a median survival of 15.1 months. Based on this result, a compassionate-use program has been established to provide pts with mCRPC the opportunity to receive the treatment, before licensing of the drug. Methods: ATU of cabazitaxel in France has been granted before its marketing authorization; all safety data from pts treated during this period were collected following a specific therapeutic use protocol. All participating physicians were instructed about the molecule by a company physician and contacted before the first treatment, on day 15 and at the end of treatment of each patient to make sure that all G3/4 and serious adverse events were collected. Results: We report baseline characteristics and safety data from the 184 pts treated in 92 French centers. Median age was 67.2 years (46 - 92), ECOG performance status was 0-1 for 85% of pts, 88% had bone metastases and 21% had visceral metastases. All the pts had received prior docetaxel, 55% had discontinued for disease progression; 85% of the pts received previously 1-2 lines of chemotherapy. Pts received a median of 3 cycles of cabazitaxel (1-6). Rates of grade 3-4 hematological toxicities were: neutropenia grade≥ 3 (4%), febrile neutropenia (3%), all resolved. All grade other toxicities were: nausea (0.5%), diarrhea (2.7%) and fatigue (0.5%). No treatment-related death was reported. Conclusions: The ATU program provides additional safety information on cabazitaxel in the real-life setting; they are consistent with the TROPIC study safety results. The incidence of neutropenia grade≥ 3 (4%) and febrile neutropenia (3%) appears to be lower than expected. Therapeutic use protocols such as these can be helpful for physicians when new therapies become available. Proactive education of healthcare givers on AEs management could be considered when new treatments are introduced.
Bone metastasis (BM) based on SEER registry versus Medicare claims among metastatic prostate cancer (PCa) patients (pts) in SEER-Medicare.
Authors: Onukwugha Ebere , Mullins C. Daniel , Yong Candice , McNally Diane L. , Seal Brian S. , Hussain Arif
Published: March 2020

e15148

Background: There is questionable reliability of administrative claims data to identify BM, yet historically such claims were the only source for identifying BM in SEER-Medicare (SM). Starting in 2004, SEER provided tumor registry information on incident BM. We compared frequencies of BM using registry and claims data among men diagnosed with PCa. Methods: We analyzed pts aged 66 and older from the linked SM database. Pts with stage IV (M1) PCa diagnosed between 2004 and 2007 were followed until death or censoring. Identifying pts with BM using claims required at least one inpatient or outpatient claim with a diagnosis code of 198.5 within (i.e., +/-) 1 month of the SEER diagnosis month (designated BMclaims-90) or at any time during follow up (designated BMclaims-ever). BM identified using SEER was based on an indicator for bone metastasis at diagnosis using the AJCC M1b classification (designated BMseer). We calculated the sensitivity and specificity of BM at diagnosis in claims (BMclaims-90) with respect to the incident BM data in SEER, assuming BMseer to be the gold standard. Results: Application of inclusion/exclusion criteria resulted in 3,664 stage IV (M1) PCa pts. Average age was 79 years, 13% were African American, and 61% had poorly/un-differentiated tumors. BMseer (n=2,301; 63%) was higher than BMclaims-90 (n=1,979; 54%) and lower than BMclaims-ever (n=2,878; 79%). Assuming BMseer as the standard measure of BM at diagnosis, BMclaims-90 had 58.8% sensitivity (n=1,353), 54.1% specificity (n=737), and 68.4% positive predictive value for identifying BM at diagnosis. Among men with BM identified using BMseer, 84% (1,931) had BMclaims-ever and the median (min; max; average) time to the first BM claim was 0.9 (-2.6; 57.1; 3.9) months. Among men with BM identified using BMclaims-90, the median (min; max; average) time to the first BM claim was 0.6 (-1.0; 2.0; 0.7) months. Conclusions: The incidence of BM in PCa pts differs between a commonly-used algorithm to identify BM in claims data and the AJCC staging information in tumor registry data. There was moderate concordance between the claims-based measure and the SEER-based measure of BM at diagnosis.
Evaluation of the response to cabazitaxel of a docetaxel-responsive hormone-refractory prostate tumor xenograft model (HID28).
Authors: Bourre Ludovic , Nicolle Delphine , Legrier Marie-Emmanuelle , Yvonnet Vanessa , Charpentier Julie , Poupon Marie-France , Vrignaud Patricia , Geffriaud-Ricouard Christine , Oudard Stephane , Judde Jean-Gabriel
Published: March 2020

e15161

Background: Docetaxel was the first cytotoxic treatment demonstrating a survival benefit in metastatic castration-resistant prostate cancer (mCRPC) patients. Recently, cabazitaxel (a novel taxane) and abiraterone acetate (specific inhibitor of CYP17) have demonstrated a significant survival benefit in mCRPC patients progressing after receiving a docetaxel – containing regimen. Here we compare the antitumor efficacy of docetaxel, cabazitaxel and abiraterone acetate in the HID28 hormone-refractory human prostate carcinoma xenograft. Methods: HID28 tumor bearing nude mice received 20 mg/kg of docetaxel (IP, q3wk x 2), cabazitaxel at 15 and 20 mg/kg (IP, q3wk x 2) and abiraterone acetate at 50 mg/kg (PO, qdx21). Median tumor growth inhibition (T/C%) was evaluated as well as time course androgen receptor expression (4, 8 and 24h post dosing) by western blot analysis. Results: Docetaxel (20 mg/kg) inhibited tumor growth with a T/C%= 16.7% at D35, 2 partial (PR) and 1 complete (CR) tumor regressions, and with relapse of all tumors (6/6) observed at D42. Cabazitaxel demonstrated dose-dependent efficacy at D35 with T/C%= 10.8% and 1.4% for 15 and 20 mg/kg doses respectively. At a cabazitaxel dose of 15 mg/kg, 4/10 PR and 3/10 CR were observed, whereas 4/10 PR and 6/10 CR were observed at 20 mg/kg. At D42, 6/6 tumor relapses were observed at 15 mg/kg; whereas, only 3/6 relapses were observed at 20 mg/kg. No anti-tumor activity was demonstrated with abiraterone acetate as well as no significant decreases in testosterone levels compared to the vehicle group. Tolerability was good for all treatment groups, with a transitory maximum mean body weight loss of 12%, 6 days after treatments. Androgen receptor western blot expression analysis after 4, 8 and 24h post dosing demonstrated no significant difference between groups and over time. Conclusions: Cabazitaxel and docetaxel showed similar tolerability at equivalent dose levels. Cabazitaxel demonstrated superior antitumor efficacy over docetaxel at equivalent dosing in the HID28 hormone-refractory tumor model. These results support the clinical development of cabazitaxel in first line treatment of mCRPC patients.
Elevated serum activin A and survival in CRPC.
Authors: Ali Suhail M. , Zubritsky Lindsey , Jacobus Susanna J. , Leitzel Kim , Regan Meredith M. , Nakabayashi Mari , Knight Robert D. , Laadem Abderrahmane , Sherman Matthew L. , Lipton Allan , Kantoff Philip
Published: March 2020

e15170

Background: The prognosis of castration-resistant prostate cancer (CRPC) varies widely. Activin A is a ligand in the TGF-B superfamily that regulates cell proliferation, apoptosis, differentiation, and immune responses. In patients with multiple myeloma, elevated activin A is associated with advanced disease and poorer overall survival (OS). Methods: 60 Metastatic CRPC patients whose serum samples were stored at the Dana-Farber Cancer Institute were used for this study. Plasma activin A levels were measured using ELISA (R&D Systems, Minneapolis, MN). Levels of activin A within key patient and disease characteristics were analyzed using the Wilcoxon rank sum test. OS distributions by activin A tertile status were estimated with Kaplan-Meier (KM) and compared with the logrank test. Cox regression was used to produce hazard ratios (HR). Results: In this cohort of 60 patients with metastatic CRPC, median age at diagnosis was 62y, median PSA was 15.3 ng/mL and 37% had a biopsy Gleason score (GS) >8. The index blood draw was a median of 32.9 mo from androgen-deprivation therapy. Median age and PSA at blood draw were 71y and 23.5 ng/mL. At the time of blood draw, 57% of patients had bone only metastasis, 30% were receiving primary or 38% secondary hormonal therapy, and 30% were receiving chemotherapy. Median survival follow-up was 17 months after blood collection (27 deaths). Activin A levels were 621.9 pg/mL (median) and 1382.7 pg/mL (mean). Activin A levels were elevated among older patients (> 65y) and only within patients with higher PSA (>20 ng/mL) at blood draw. KM estimates of median OS (months) for the low, mid and high serum activin A tertile groups were 19.7, 13.8 and 5.4, respectively (p<0.001). The HR (referent low) was 1.4 (95% CI: 0.5-4.5) for the mid and 5.6 (95% CI: 2.1-14.9) for the high tertile. OS was significantly different within age and GS groups, but not within PSA groups. In multivariable analysis, tertile activin A remained significant (p<0.02) when adjusted separately for age at diagnosis, biopsy Gleason score, and serum TIMP-1 (reported previously). Conclusions: Elevated serum activin A predicted for shortened OS in metastatic CRPC, and deserves further study as a biomarker of aggressive disease.
Temsirolimus (TEM) maintenance therapy after response of castration-resistant prostate cancer (CRPC) to docetaxel (TAX).
Authors: Emmenegger Urban , Booth Christopher M. , Berry Scott R. , Sridhar Srikala S. , Winquist Eric , Bandali Nesan , Chow Annabelle , Lee Christina R. , Xu Ping , Man Shan , Kerbel Robert S. , Ko Yoo-Joung
Published: March 2020

e15177^

Background: There are no standard treatments for men who have demonstrated a good response to TAX without signs of progression. The mTOR pathway is involved in many aspects of CRPC, and mTOR inhibitors have shown significant anti-CRPC activity in preclinical testing. Therefore, we designed a phase II trial to explore whether maintenance therapy with TEM has the potential to prolong response to TAX without compromising quality of life. Methods: For this single-arm, multicenter phase II trial we recruited CRPC pts with documented treatment response by PSA (> 50% decline from baseline) or RECIST (1.0) criteria following ≥ 6 to 10 cycles of TAX (75 mg/m2 q3wks). Subjects received weekly TEM (25 mg iv x 4/cycle). The primary endpoint was time to treatment failure (TTF; RECIST or symptomatic progression). Secondary endpoints included safety (NCI-CTCAE v3.0), quality of life (FACT-P, PPI), changes in PSA, objective tumor response rate, and overall survival. We were also studying surrogate markers of TEM activity, including the enumeration of circulating endothelial cells (CEC) as a potential indicator of the antiangiogenic effects of TEM. Results: 19 pts have been enrolled to data after a median of 7 cycles of TAX. The mean age was 68 years (range 51-82), and the median baseline PSA 17.3 (0.02-380.7). 15 pts had received prior local radiation therapy, 6 surgery. 17 pts had bone metastases, 9 visceral and 8 nodal disease. Pts received a median of 4 cycles of TEM (maximum 23 and continuing), resulting in a median TTF of 5.8 (95%CI 3.8-9.2) months. No PSA responses were seen (time to PSA progression 1.8 months), but 1 PR. 8 pts achieved SD. 12 pts have been discontinued due to treatment failure (RECIST [4], symptomatic [7], combined [1]), and 3 for other reasons, including TEM-associated toxicity (lymphedema [1]). TEM has been generally well tolerated without unexpected adverse events or negative impact on quality of life. The median overall survival has not yet been reached. There is a trend for TEM to reduce viable CEC amid large inter/intrapatient CEC variability. Conclusions: TEM maintenance therapy in CRPC pts that have responded to TAX appears to be well tolerated and results in meaningful prolonged TTF.
The effect of BMI at time of surgery on long-term outcome after radical prostatectomy.
Authors: Payne Ondracek Rochelle , Hayn Matthew H. , Poch Michael Adam , Davis Warren , Curtis Alexandra , Kim Hyung Lae , Morrison Carl D , Mohler James , Marshall James Roger
Published: March 2020

e15203

Background: Body mass index (BMI) at time of surgery was determined among 715 radical prostatectomy patients. The association of BMI with a range of treatment outcomes was considered. Methods: The associations of BMI at time of radical prostatectomy (RP) with disease stage and aggressiveness and long-term outcome were evaluated among 715 patients treated with RP at Roswell Park Cancer Institute between 1993 and 2005. Clinical and pathological aggressiveness indicators included clinical Gleason sum and tumor stage (2002 TNM), highest preoperative PSA, pathological Gleason sum and tumor stage (2002 TNM) and surgical margin status. Ten post-RP recurrence definitions were considered: 1) PSA ≥ 0.2 ng/ml; 2) PSA ≥ 0.4 ng/ml (with 1 confirming value); 3) 1 or more post RP treatments (ADT, radiation, chemotherapy); 4) PSA doubling time < 12 months; 5) PSA doubling time < 9 months; 6) PSA doubling time < 6 months; 7) NCCN definition of PSA failure; 8) AUA definition of PSA failure; 9) diagnosis of metastatic CaP; and 10) death from CaP. Results: Of the 715 men, 33 developed metastatic prostate cancer, and 17 died of prostate cancer. 246 men had BMI ≥ 30. BMI was not significantly associated with clinical or pathological aggressiveness criteria. These analyses showed that there is a trend towards higher risk of the development of metastasis or death for men with BMI ≥ 30, although the association with high BMI and these failure types is not significant. With adjustment for the most significant tumor aggressiveness features (clinical Gleason sum, pathological tumor stage, pathological Gleason sum, and surgical margin status) in proportional hazards regression, men with BMI ≥ 30 had consistently lower risk for all definitions of recurrence except metastasis and death, although no hazard ratios were significant. In contrast, men with higher BMIs had higher risk for metastasis and death from prostate cancer, although neither association is statistically significant. Conclusions: Men with higher BMIs show similar to slightly reduced risk for PSA-based recurrence definitions. Men with higher BMIs had slightly higher risk, though not significant, for metastasis and death. These results seem to support theories that PSA is diluted in men with higher BMIs.
Association of calcium channel blocker use with prostate cancer aggressiveness, progression-free survival, and overall survival.
Authors: Poch Michael Adam , Mehedint Diana , Curtis Alexandra , Attwood Kristopher , Wilding Gregory E. , Payne Ondracek Rochelle , Underwood Willie , Schwaab Thomas , Guru Khurshid , Mohler James , Heemers Hannelore
Published: March 2020

e15204

Background: Epidemiological studies indicate that the use of calcium channel blockers (CCB) is inversely related to prostate cancer (PCa) incidence. The goal of this study was to examine the association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) or outcome after RP. Methods: Information on medication use, PCa aggressiveness and outcome after RP was retrieved from a prospective database that contains clinical and follow-up (FU) data for all men that have undergone RP at the Department of Urology at Roswell Park Cancer Institute since 1992. The database was queried for anti-hypertensive medication use at the time of diagnosis for all patients with ≥ 1 year FU. Prostate cancer aggressiveness (risk status) and recurrence were defined using NCCN guideline definitions. Cox regression models were performed to compare the distribution of progression-free survival (PFS) and overall survival (OS) with adjustment for covariates. Chi-Square test was used to assess the relationship between CCB use and PCa aggressiveness. Results: 875 men were included in the study. At diagnosis, mean age was 60 (SD ± 7) years and mean serum PSA value was 7.4 (SD ±7.4) ng/ml. 48%, 37%, and 15% of patients had low risk, intermediate risk, or high risk PCa, respectively. 104 (12%) had a history of CCB use. CCB users and non-users were similar by PSA at diagnosis (p=0.97) and tumor aggressiveness (p=0.88). Patients taking CCB were more likely to be older (p=0.023), have a higher BMI (p=0.006) and use additional anti-hypertensive medications (p<0.01). Margin status after radical prostatectomy was similar (p=0.30) between the two groups. Median FU was 42 months. PFS (p=0.82, HR 95% CI: 0.63-1.44) and OS (p=0.72, HR 95% CI: 0.42-3.52) did not differ between the 2 groups. Adjusting for age and PCa aggressiveness did not alter the results observed for PFS (p=0.44, HR 95% CI: 0.62–1.41) and OS (p=0.50, HR 95% CI: 0.04-3.48). PCa aggressiveness was associated with PFS (p=0.001) in the multivariate model. Conclusions: CCB use does not affect PCa aggressiveness at time of diagnosis or improve PFS or OS.
Borderline ovarian tumors: Long-term survival and preservation of fertility.
Authors: Gercovich Natasha , Garcia Gerardi Carlos , Gil Deza Ernesto , Morgenfeld Eduardo L. , Rivarola Edgardo G. J. , Gercovich Felipe G.
Published: March 2020

e15508

Background: Borderline ovarian tumors, also called low-malignancy potential tumors, are infrequent tumors present predominantly in pre-menopause women. Their evolution after surgical treatment is generally very good. The main objective of this paper is to show the evolution of a group of borderline tumors treated at our institution. Methods: Between January 1, 2000 and January 1, 2010, 36 patients diagnosed with ovarian borderline tumors were examined by two independent pathologists, according to the guidelines established by the USA Association of Directors of Anatomic and Surgical Pathology. These patients were followed at IOHM and comprise this paper’s study group. Results: Population Characteristics: Mean Age: 41 years (Range: 20-85). Affected Ovary (Right: 17 pts; Left: 14 pts; Both: 5 pts). Pathology: Mucinous (17 pts), Serous (16 pts), Clear, Brenner and Endometroid Cells (1 pt each). Stages: IA (24 pts), IB (5 pts), IC (2pts), IIIA (4 pts), IIIC (1 pt). Five patients presented non-invasive peritoneal implants and three presented positive peritoneal liquid. All patients were surgically treated: 28 with total anexohisterectomy (TAH) and 8 with unilateral ooforectomy. No patient was given any chemotherapy or radiotherapy treatment. Four patients did not attend follow-up consultations and were lost after 4, 6, 12 and 29 months with no evidence of disease (NED). Thirty-two patients were followed bi-annually during the first five years and annually thereafter. One patient became pregnant after the surgery. All patients are alive and NED with an average follow up of 50 months (range: 29-133). Conclusions: 1) Although half the cases in the study were under 35 years old, there were 12 tumors present in patients over 50 years of age and 1 borderline tumor present in an 85 year old patient. 2) Surgically treated ovarian borderline tumors have a high chance of being curable without the need of chemotherapy or radiotherapy. 3) Conservative surgery in young patients allows a conservation of fertility, provided they are subject to an adequate follow-up.
Menopausal and sexual symptoms following radiotherapy in survivors of advanced cervical cancer.
Authors: Pushpalatha Kameshwarachari , Sharma Dayanand , Julka Pramod Kumar , Kumar Sunesh , Rath G K
Published: March 2020

e15518

Background: With ever-increasing number of cancer survivors nearing 12 million, a majority of women will face vaginal health issues related to their disease and/or treatment. Hypothesis is that there is direct damage to ovarian follicles as a result of ionizing radiation leading to follicular atrophy and decrease in ovarian follicular reserve. Cancer treatment with radiotherapy induces menopause-causing estrogen-deprivation symptoms. Hence this study was conducted to investigate the frequency of radiation-induced menopausal and sexual symptoms in cervical cancer survivors Methods: A cross-sectional study was conducted between Feb-June 2011 on cohort of 55 advanced cervical cancer patients treated with pelvic radiation of 50.4 Gy in 28 fractions over 5.5 weeks and concurrent Cisplatin, followed by intracavitary boost of 15 Grays. Women aged 55 or older and/or postmenopausal at the time of the survey were excluded. By using a questionnaire, frequency of menopause was tried to elicit along with associated sexual symptoms like hot flushes, vaginal dryness, mood swings, dyspareunia, loss of libido, botheration. Results: The average age and parity were 38.8 years and 3.6 respectively. Amenorrhoea was found in all patients. 27 (49%) patients were asymptomatic. Among 28 (50.9%) symptomatic patients, we found hot flushes in 21 (38.2%), vaginal dryness in 38 (69%), mood swings in 12 (21.8%), dyspareunia in 27 (49%), loss of libido in 26 (47.2%), bothersome in 28 (50.9%). Conclusions: Menopausal symptoms were associated with other health-related issues known to compromise the quality of life. These results highlight the need to better acknowledge and define the utility of hormonal therapy in this population. Recommendations need to be provided to treating gynaecologists and Oncologists to identify, treat and promote vaginal health. Vaginal health issues can be reduced by dedicating a small duration of time to educate the cancer survivors on hormonal/non-hormonal vaginal health strategies.
Nonpegylated liposome-encapsulated doxorubicin (NPLED) and cyclophosphamide in the treatment of platinum-resistant ovarian cancer: Final results of a phase II study.
Authors: Sambataro Daniela , Caruso Melania , Di Blasi Concetta , Lavenia Giuseppe , Asero Salvatore , Amadio Placido , Mattina Marco , Burrafato Giovanni , Longhitano Laura , Rapisardi Stefania , Cordio Stefano Sergio , Ettore Giuseppe , Bordonaro Roberto
Published: March 2020

e15544

Background: Platinum resistant-refractory ovarian cancer (PRROC) patients have a poor outcome; single-agent therapy is still the gold standard, with overall response rate lesser than 20% and progression-free-survival is not higher than 4 months. Methods: We tested safety and activity of a two-drugs-regimen containing NPLED and cyclophosphamide in a phase II open label study. From October 2007 to October 2011 thirty-two patients with platinum-resistant/refractory disease were enrolled. Enrolled patients were pretreated with a median number of 2 lines of chemotherapy, ranging from 1 to 5. NPLED and cyclophosphamide were administered at the dose of 60 mg. and 600 mg p.s.m. respectively. Results: Patients received a median number of three cycles of chemotherapy. A total of 145 cycles were administered: as G3 toxicities we registered emesis (6%), diaorrhea (3%), asthenia, and alopecia. No grade 4 adverse events occurred. Among the 30 patients evaluable for response we observed 5 (17%) partial responses and 10 (33%) stable diseases. The median progression-free-survival was 13 weeks and the median survival was 46 weeks. Conclusions: These results are similar to other data reported in literature. In conclusion we may affirm that the association of NPLED and cyclophosphamide is active and safe when administered in PRROC, but it don’t modify the prognosis of this subset of patients.
ADXS11-011 immunotherapy: Preliminary safety data from two P2 studies in women with CIN 2/3 and with recurrent/refractory cervical cancer.
Authors: Petit Robert G. , Aqua Keith A. , Basu Partha
Published: March 2020

e15546

Background: ADXS11-001 immunotherapy is a live attenuated Listeria monocytogenes (Lm) bioengineered to secrete a HPV-16-E7 fusion protein targeting HPV transformed cells. The Lm vector serves as its own adjuvant and infects APC where it naturally cross presents, stimulating both MHC class 1 and 2 pathways resulting in specific T-cell immunity to tumors. Here we describe the preliminary survival data associated with ADXS11-001 administration in Lm-LLO-E7-015, a randomized phase II study being conducted in India in 110 patients with recurrent/refractory cervical cancer who have been treated previously with chemotherapy, radiotherapy or both. Methods: Patients are randomized to either 3 doses of ADXS11-001 at 1 x 109 CFU or 4 doses of ADXS11-001 at 1 x 109 CFU with cisplatin chemotherapy. Naprosyn and oral promethazine are given as premedications and a course of ampicillin is given 72h after infusion thereby clearing any residual vector. Patients receive CT scans at baseline and Days 84, 184, 273, 365 and 545. The primary endpoint is 12 month survival. Results: As of January 26, 2012, 88 patients have received 200 doses of ADXS11-001; with the percentage of patients alive at 6 months at 62% (34/55); at 9 months at 41% (15/37) and at 12 months at 40% (6/15). Tumor responses have been observed in both treatment arms with 3 complete responses (elimination of tumor burden) and 4 partial responses (≥30% reduction in tumor burden) by RECIST. One serious (Gr3) adverse event and 77 mild-moderate (Gr 1-2) adverse events possibly related to study treatment have been reported in 35% (31/88) of patients. The non-serious adverse events consisted predominately of transient, non-cumulative flu-like symptoms associated with infusion that responded to symptomatic treatment, or resolved on their own within hours of treatment. Conclusions: This immunotherapy can be safely administered to patients with advanced cancer alone and in combination with chemotherapy. ADXS11-001 is well tolerated and presents a predictable and manageable safety profile. Early signs of clinical benefit merit further investigation. Updated findings will be presented at the meeting.
Does HE4 have a role in the recurrence of ovarian cancer?
Authors: Montera Roberto , Plotti Francesco , Muzii Ludovico , Terranova Corrado , Angelucci Michela , Oronzi Irma , Damiani Patrizio , Dugo Nella , Guzzo Federica , De Oronzo Maria Antonietta , Ricciardi Roberto , Aloisi Alessia , Luvero Daniela , Portuesi Rosa Alba Valentina , Scaletta Giuseppe , Capriglione Stella , Linciano Francesca , Gennari Paolo , Benedetti Panici Pierluigi , Angioli Roberto
Published: March 2020

e15550

Background: Human epididymis protein 4 (HE4) has been recently described as a new marker for early ovarian cancer, with higher sensitivity (76.9%) compared to CA125. This is the third study in literature on the role of HE4 in recurrence of ovarian cancer and the first evaluating the sensitivity of HE4 and CA125 in these patients Methods: Plasma was obtained 24 hours before secondary cytoreductive surgery from consecutive patients with suspicious recurrence ovarian cancer operated from November 2010 to April 2011 at University Campus Bio-Medico of Rome. CA125 levels were evaluated by a one-step "sandwich" radioimmunoassay. HE4 levels were determined using the HE4 enzymatic immune assay. The CA125 cut-off was less than 35 U/mL. Two cut-off were considered for HE4: less than 150 pmol/L (according to the manufacturer's indications) and less than 70 pmol/L. Results: Fourteen patients were histologically confirmed as recurrence ovarian cancer. Mean Ca125 plasma concentration was 31.95 ± 22.09 U/mL (range 1.1 – 64.3). Mean HE4 plasma concentration was 225.83± 286.82 pmol/L (range 21.61- 633.6). The sensitivity of CA125 was 35.7 %. The sensitivity of HE4 was 71.4% and 28.6% above the cut-off of 70 pmol/L and 150 pmol/L, respectively. The dual marker combination of CA125 and HE4 at 70 pmol/L cut-off yielded the highest sensitivity (85.7%) to detect recurrence ovarian cancer. Conclusions: Even if a standard cut-off point has not been determined, this study suggested that HE4 may potentially be a more sensible marker for recurrence ovarian cancer than CA125 and the association between CA125 and HE4 at cut-off of 70 pmol/L seems to yield the highest sensitivity.
Surgical primary treatment of stage IVA cervical cancer: A multicenter retrospective study.
Authors: Damiani Patrizio , Plotti Francesco , Zullo Marzio Angelo , De Cicco Nardone Carlo , Montera Roberto , Cafà  Ester Valentina , Guzzo Federica , Ricciardi Roberto , Aloisi Alessia , Montone Eva , Hyseni Entela , Luvero Daniela , Capriglione Stella , Lopez Salvatore , Scaletta Giuseppe , Miranda Andrea , Benedetti Panici Pierluigi , Angioli Roberto
Published: March 2020

e15551

Background: The aim of the present study is to describe feasibility, surgical technique, perioperative data, early and late complications of anterior and total pelvic exenteration after neoadjuvant chemotherapy as primary treatment for stage IVa cervical cancer. Methods: It is a retrospective study which included 73 consecutive patients affected by stage IVa cervical cancer who required anterior or total pelvic exenteration referred to 3 international gynaecologic oncology centres. The steps of this extirpative surgical procedure were: 1) staging laparotomy; 2) frozen section biopsy of the paraaortic lymph nodes; 3) systematic lymphadenectomy, radical hysterectomy with adnexectomy and total or anterior pelvic exenteration; 4) continent urinary diversions and low colorectal anastomosis if it was possible. Results: The treatment of patients affected by FIGO stage IVA cervical cancer remains one of the most complex procedures gynecologic oncologists are faced with. Our study focused on clinical and operative data , in terms of overall survival (OS) and disease free survival (DFS) at 5 years. 5-year OS of our series was 43%. Conclusions: The surgical treatment of stage IVA cervical cancer appears therefore a suitable and valid alternative. Stage IVA cervical cancer patients in good general condition, with a disease resectable with clear surgical margins, should be considered for primary exenteration in referral centers where the surgical experience to perform this procedure is available.
Laparoscopic lymphocele fenestration as first-line measure for gynecologic cancer patients after retroperitoneal lymph node dissection: 10-year analysis of safety, feasibility, efficacy, and recurrence rate.
Authors: Runnebaum Ingo B. , Radosa Marc P. , Diebolder Herbert , Winzer Harald , Anschuetz Julia , Camara Oumar
Published: March 2020

e15566

Background: The occurrence of lymphoceles is a notorious complication occurring after retroperitoneal lymph node dissection (LND) frequently treated by repetitive percutaneous needle punctures associated with a high risk of wound infection or bowel injury. Methods: We analyzed 10 years of single-center experience with laparoscopic lymphocele fenestration as a first-line measure in gynecologic cancer 102 consecutive patients with a history of retroperitoneal LND (53.4 years; range: 22–80) who underwent laparoscopic lymphocele fenestration at our department between January 2001 and December 2010 for a symptomatic lymphocele. Results: A total of 132 lymphoceles have been fenestrated in 102 patients by laparoscopy, onaverage 5.3 months (SD: 6.3 months) after the initial LND. Mean follow-up of the patients was 60.4 months. Mean duration of surgery was 115.6 minutes and the average intra-operative blood loss per patient was 146 ml. Overall conversion rate to laparotomy was 7.8 %. The rate of intraoperative and postoperative minor and major complications was significantly higher in patients after pelvic plus paraaortic LND (23.8 %) compared to those after pelvic LND alone (3.6 %; p>0.01). Two-year cumulative risk of lymphocelerecurrence was only 4.2 % with a total of 7 recurrences of lymphoceles observed. Conclusions: Laparoscopic lymphocele fenestration was safe and feasible as well as efficacious as a surgical first-line treatment option for symptomatic lymphocele following retroperitoneal LND in gynecological cancer patients with a particularly low recurrence rate.
Neoadjuvant chemotherapy versus primary debulking surgery in advanced ovarian cancer: Experience in Mexican population.
Authors: Dip Borunda Abdel Karim , Leon Rodriguez Eucario , Armengol Alonso Alejandra
Published: March 2020

e15567

Background: Primary debulking surgery is considered the standard of treatment in advanced ovarian cancer (AOC) while neoadjuvant chemotherapy is used in non resectable stages. Methods: We retrospectively analyzed 68 AOC cases from January 2000 to December 2011. 35 received neoadjuvant chemotherapy (NAC) while 33 were resected primarily and received adjuvant chemotherapy (AC). To compare both groups we used T standard test and 2 sided chi -squared. Non parametric variables were analyzed with U Mann – Whitney. Overall survival(OS) was analyzed using Kaplan Meier method with log rank test. We considered statistically significant p<0.05. (SPSS v 17). Results: The median age was 60 (NAC) vs 53(AC) years respectively. The NAC group had more advanced stage disease (FIGO IIIC/IV stage; 71/29% vs 91/9%; p=0.04). The most frequent histologic subtype in both groups was serous - papillary and histologic grade was poorly differentiated in 71 vs 72% (p=0.41). At diagnosis the median levels of ca-125 were 1,896 U/ml for NAC group vs 768 U/ml for AC group (p=0.025). After the primary treatment received the median levels of ca – 125 were 29 U/ml vs 84 U/ml (p=0.76). Platin based chemotherapy was used in 95% vs 70% respectively. Complete resection of macroscopic disease was observed in 68% of NAC vs 63% in AC respectively. No statistical differences were observed in surgical time (median 192 min vs 204 min; p=0.55) and surgical bleeding (468 vs 510ml; p=0.79). Median survival time was 23 +/-26 months for neoadjuvant and 27+/- 35 months for primary surgery (p=0.56). In a subgroup analysis of patients who received 6 neoadjuvant cycles vs perioperatory chemotherapy (3 pre and 3 postoperatory) we observed a significant survival difference, with a median of 62 months (95% CI 12-38) vs 12 months (95% CI 54 – 178) respectively (p=0.010). Conclusions: Non inferior survival or differences in surgical outcomes were observed with neoadjuvant therapy. Significant survival increase was observed in patients who received complete chemotherapy schedule before surgery, this evidence allowed to design a prospective trial in our Institution.
Retrospective analysis of stage IIIc uterine carcinoma patients: A single center experience.
Authors: Yalcin Selim , Rahatli Samed , Kucukoztas Nadire , Ozen Ozlem , Haberal Nihan , Tarhan Cagla , Dursun Polat , Dizdar Omer , Yildiz Ferah , Altundag Ozden , Ayhan Ali
Published: March 2020

e15572

Background: Stage IIIC comprises 8% of all endometrial cancers. Both local and systemic relapse risks are high. Current standard of care is adjuvant chemotherapy; however the addition of radiotherapy seems to improve outcomes in retrospective series but prospective data is lacking. We herein report outcomes of our patients with stage IIIC endometrial cancer operated and treated with adjuvant chemotherapy±radiotherapy. Methods: 29 patients with stage IIIC endometrial cancer diagnosed between 2006-2011 were included. Demographic features, tumor characteristics, treatment regimens and patient outcomes in terms of DFS and OS were analyzed. Results: Median age was 64 (41-82). Surgical procedure was TAH+BSO+BPPLND and omentectomy in 26 patients. 4 patients who were operated (TAH+BSO) in another center were restaged and BPPLND and omentectomy were performed. 13 patients (45%) had endometrioid histology, 11 (38%) had papillary serous carcinoma, 2 (7%) had clear cell carcinoma, 2 (7%) had mixed carcinoma and 1 (3%) had undifferentiated carcinoma. 6 patients had ovarian, 9 had uterine serosal involvement, 1 had positive cytology of abdominal washing, 18 (62%) had lymph node-only disease. 14 patients (48%) had positive nodes both in pelvic and paraaortic region, 9 (31%) only in pelvic region and 6 (21%) only in paraaortic region. 24 patients (83%) received chemotherapy with paclitaxel and carboplatin, 13 (45%) received external RT, 4 (14%) received brachytherapy and 3 (10%) patients received chemoradiation with weekly cisplatin or carboplatin. Median follow-up was 19 months. 10 patients recurred during follow-up and 6 patients died. All of the recurrences except one were intraabdominal. 3-year PFS was 64% and OS was 71.6%. Conclusions: With the use contemporary chemotherapy regimens and radiotherapy, we achieved ~70% 3-year survival rate in stage IIIC endometrial carcinoma patients with 45% of the patients having high risk histologies (serous and clear cell). We propose that combined adjuvant chemotherapy and radiation might improve survival in patients with advanced stage disease compared to either modality alone. Results of GOG258 and PORTEC 3 trials should be awaited for definitive conclusions.
In vitro chemoresponse assay results and population clinical response rates in women with ovarian cancer.
Authors: Richard Scott Daniel , McClure Candace , Leath Charles A. , Herzog Thomas J. , Gan Christine M. , Krivak Thomas C. , Cibull Michael , Coleman Robert L.
Published: March 2020

e15578

Background: While platinum-based chemotherapies have been identified as the most effective agents in ovarian cancer, they are not effective in all women. An in vitro assay that determines whether platinum agents are likely to be effective for individual patients could have clinical utility. This study determines whether in vitro platinum sensitivity rates are similar to published population response rates for ovarian cancer and examines differences in platinum sensitivity across histologic subtypes. Methods: In vitro chemoresponse testing (ChemoFx, Precision Therapeutics, Pittsburgh, PA) was performed on tumors from 3,130 patients with primary or recurrent epithelial ovarian cancers. Histologic subtypes included serous, endometrioid, clear cell, and mucinous. Primary cancers, stages II-IV, were examined. Tumors were classified as responsive (R), intermediately responsive (IR), or non-responsive (NR) to chemotherapy. The rates of pan-resistance (Pan R), defined as non-responsive to all agents tested, was also examined in both primary and recurrent tumors. Statistical analyses were conducted using the Chi-square test with Bonferroni correction where appropriate. Results: Of 3,130 eligible patients, 2,335 had stage II-IV primary tumors (75%); the remaining 795 (25%) were recurrent. Overall, 77% of primary tumors were responsive (R or IR) to combination carboplatin/paclitaxel (CP). CP response rate was significantly different across histologic subtypes (p<0.001), with serous tumors exhibiting the highest response rate (79%). CP response was significantly greater in serous tumors (79%) when compared to mucinous tumors (65%; p=0.03). CP response was significantly greater in primary tumors (77%) when compared to recurrent tumors (65%)(p<0.001). In addition, the rate of pan R was significantly greater in recurrent tumors (26%) compared to primary tumors (15%)(p<0.001). Conclusions: ChemoFx response rates to PC are consistent with expected population response rates. As anticipated, more aggressive histologic subtypes were less responsive to CP in vitro. These data suggest that the ChemoFx assay provides tumor-specific information that may assist in chemotherapy decision making.
Toll-like receptor 7 and 9 (TLR 7 and TLR 9) expression in biopsies of in situ cervical cancer.
Authors: Moreno-Eutimio Mario Adan , Aragon-Franco Raul , Lopez-Macias Constantino , Silva Alejandro J. , Astudillo Horacio
Published: March 2020

e15584

Background: In order to analyze the expression of TLR 7 and TLR 9 in cervix biopsies, we evaluated the expression of these TLRs in cervical carcinoma in situ tissue and peritumoral inflammatory tissue biopsies by immunohistochemistry. Methods: We reviewed 276 uterine cervix biopsies of Clinical Specialties Women's Health Directorate of the Ministry of National Defense (between 2009-2010); the biopsies have the following histopathological diagnosis: 124 CIN I, 68 CIN II, 34 CIN III, 21 invasive cancer and 29 cancer in situ. Results: It was observed that peritumoral inflammatory tissue receptor was expressed positively in 89.6% in cervical cancer tissue in situ, the receptor was expressed positively in 68.9% and the negative expression was 31.1%, proving that in the peritumoral inflammatory tissue compared with in situ cervical cancer was increased expression of TLR 7. In the case of the expression of TLR 9, peritumoral inflammatory tissue, expressed positively in 24 samples and 5 samples were negative expression in the tissue in situ cervical cancer samples identified 20 positive and 9 negative samples. By analyzing the intensity of the expression of TLR 7 in cervical cancer tissue in situ, we found 16 samples with focal positive (+), 3 samples with diffuse positive (+ +) and 1 sample with positive (+ + + ), while in peritumoral inflammatory tissue found 13 samples with focal positive (+), 10 samples with diffuse positive (+ +) and 3 samples with positive results (+++). By analyzing the intensity of the expression of TLR 9 in cervical cancer tissue in situ, we found 14 samples with focal positive (+), 5 samples with diffuse positive (+ +) and 1 sample with positive (+), in contrast to the peritumoral inflammatory tissue was found 7 samples with focal positive (+), 13 samples tested positive diffuse (+ +) and 4 samples with positive results (+++). Conclusions: These results show that no significant difference between the expression of TLR 7 () and TLR 9 () in the peritumoral inflammatory tissue and tissue in situ cervical cancer found a decrease in the expression of TLR 7 and TLR 9 in tissue in situ cervical cancer compared with the expression in the peritumoral tissue inflammation.