bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity and safety of carboplatin and paclitaxel followed by capecitabine and radiation as adjuvant therapy for gastric cancer (GC)
Authors: Mobayed M. , Philip P. A. , Shields A. F. , Heilbrun L. , Washington T. , Vaishampayan U. , Venkatramanamoorthy R. , El-Rayes B. F.
Published: March 2020

15162

Background: Adjuvant 5FU based chemo-radiotherapy is considered the standard of care for the treatment of GC. However, the reduction in distant metastases has not been significant indicating the poor systemic effect of this regimen. A regimen of carboplatin and paclitaxel followed by capecitabine and radiation was adopted at the Karmanos Cancer Institute to improve the systemic effects of adjuvant therapy and to utilize the significant antitumor effects of taxanes demonstrated in advanced GC. Methods: We reviewed the outcomes of 21 consecutive patients with GC who were treated with carboplatin (AUC 5 mg/ml x min) and paclitaxel (175–200 mg/m2), followed by concurrent capecitabine (1600–2000 mg/ m2) and radiation (45–50.4 Gy) since January, 1999 for curatively resected GC. Patients received a total of 4–6 cycles of carboplatin and paclitaxel. Results: The median age at diagnosis was 60 years old. Sixteen patients had stage 3 disease and 7 of them had positive margins (R1/R2 resection), 3 patients were stage 2 and 2 patients were stage 1 and both groups had negative margins; all patients had D1/D2 lymph node dissection. Thirteen patients had recurrent disease, 10 of whom had distant metastases. The median recurrence free survival was 12.3 months (90% CI; 9.7–27.7 months). Seven patients are still alive. The median OS was 16.0 months (90% CI; 13.3- 28.8 months). The median follow up for OS was 30.4 months. Grade 3–4 hematologic toxicities were found in 7 patients (33.3 %). Non-hematologic toxicities included grade 3 diarrhea in 3 patients (14%), severe fatigue in 2 patients (10%). No treatment related deaths were observed. Conclusions: Carboplatin and paclitaxel alongside radiation plus capecitabine is a well tolerated regimen in the adjuvant setting. The activity of this regimen in this relatively high risk group of GC patients is of interest for future development.

No significant financial relationships to disclose.
Metronomic capecitabine in advanced patients with hepatocellular carcinoma (HCC): Preliminary results
Authors: Brandi G. , Fanello S. , Piscaglia F. , Falanga A. , Bolondi L. , Flori S. , Derenzini E. , Palassini E. , Fedele M. , Biasco G.
Published: March 2020

15163

Background: No standard therapies are available for HCC patients (pts) ineligible for curative treatments. HCC has a rich neovasculature and neoangiogenesis is a negative prognostic factor: a high density of microvessels and hyperexpression of VEGF correlates with an increased propensity for invasion and metastatization and with a decreased DFS after resection. High level of circulating endothelial progenitors cells (CEPc) are related with insurgence and progression of HCC. Phase II trials with antiangiogenic agents in monotherapy had a response rate lower than 10% but stable disease (SD) is encouraging ranging between 30 and 60%. Retrospective analysis of standard capecitibine showed a response of 11% and similar SD rate. Experimental data on solid tumors suggest that metronomic CT prolongs inibihition of tumor growth, avoiding CEPc mobilization. Methods: Starting in september 2006, twenty-two patients were started on treatment (19 male; median age 63.7, range 47–82 ). BCLC (Barcelona Consensus Liver Cancer): 5 pts = B; 17 pts = C; Child: 12 pts =A, 8=B, 2=C. 14 pts had portal thrombosis. 15 pts were treated in front line, 7 in second line (4 pts previously treated with Sorafenib and 3 with experimental protocol of CPT-11 HAI; ASCO 2006 Abs 14061 ). The first cycle was carried out with standard capecitabine (2000 mg/sq.mt; 14 over 21 days), followed by metronomic capecitabine (1300 mg) without interruption. To compare the angiogenic role of metronomic capecitabine versus standard administration, VEGF and trombospondine have been dosed at baseline and after the first cycle of standard capecitabine and after one month of metronomic capecitabine. The response has been assessed by CT scan every three months. Results: Five out of 22 patients have been dismissed for toxicity (liver failure) during the standard capecitabine treatment. Among the 17 remaining patients, two have discontinued the treatment due to toxicity (liver failure) during the metronomic treatment and 10 have accomplished at least the first month of metronomic schedule. 6 patients have been evaluated for response: 2 PR (one second line), 3 SD (all in second line), 1 PD (second line). Conclusions: Metronomic capecitabine seems to have a better tolerability than standard schedule and promises good efficacy.

No significant financial relationships to disclose.
Prognostic factors in metastatic gastric cancer patients (pts) treated with second-line chemotherapy
Authors: Catalano V. , Graziano F. , Santini D. , Baldelli A. M. , Giordani P. , Vincenzi B. , Rossi D. , Alessandroni P. , Tonini G. , Catalano G.
Published: March 2020

15169

Background: Currently, there is no established second-line chemotherapy for pts with advanced gastric cancer who failed to respond or progressed after a first-line chemotherapy. Many of these pts still have a good performance status or have symptoms to be palliated at the time of first-line failure and are candidates for second-line chemotherapy. However, phase II trials demonstrate divergent results about pts more likely to benefit from second-line chemotherapy. We retrospectively analyzed the influence of various clinicopathologic factors on the survival of pts treated with second-line chemotherapy. Methods: Analysis is based on the data of 169 pts consecutively treated at 3 oncology department with a second-line chemotherapy. Univariate and multivariate analyses were performed to determine prognostic factors of survival. The variable used for analysis were: sex, age, ECOG performance status, a weight loss > 5 Kg in the last month; site of primary tumor, histopathology; hemoglobin, serum albumin, and CEA levels, number and site of metastatic disease, response to and time-to-progression (TTP) with the first- line chemotherapy. Results: The variables predictive of better survival were: ECOG PS 0–1 (p<0.001), no weight loss (p=0.001), hemoglobin level > 10 g/dl (p=0.01), CEA level <50 U/ml (p<0.02), number of metastatic sites = 2 (p=0.002), TTP of the first-line chemotherapy > 4 months (p=0.008). Peritoneal carcinomatosis was predictive of poor survival only when associated with one or more signs or symptoms as vomiting, anorexia, abdominal pain, ascites(p=0.03). Four factors were independently associated with better overall survival: ECOG PS 0–1 (p=0.002; HR 0.46; CI 95%, 0.29–0.75), CEA level <50 U/ml (p=0.008; HR 0.54; CI 95%, 0.35–0.85), one or two metastatic sites of disease (p=0.01; HR 0.58; CI 95%, 0.39–0.88), and TTP of the first-line chemotherapy > 4 months (p=0.02; HR 0.66; CI 95%, 0.45–0.95). Conclusions: In the absence of data deriving from randomized, controlled, clinical trials, this analysis suggests that some clinical factors may help clinicians to better select groups of pts with gastric cancer more likely to benefit from a second-line chemotherapy.

No significant financial relationships to disclose.
Treatment of locally advanced esophageal carcinoma with induction cisplatin-paclitaxel-5FU (PTF) before local therapy
Authors: Fernandez-Rodriguez R. , Ancizar N. , Lopez de Argumedo G. , Ruiz de Lobera A. , Lopez Vivanco G. , Gil Negrete A. , Sancho A. , Carrera S. , Munoz A. , Mane J. M.
Published: March 2020

15174

Background: We analyse induction therapy with PTF before local definitive therapy in terms of response, resectability, toxicity and survival. Methods: Patients (pts) with locally advanced esophageal carcinoma were included. Treatment: Paclitaxel 175 mg/m2 and CDDP 75 mg/m2 on day 1 and 5FU 800 mg/m2/day, days 1–4, every 21 days. After 2–3 cycles surgery is considered. If unresectable, Radiotherapy (64 Gy) and concomitant Carboplatin (60 mg/m2, d 1–5 during 1st and 4th week of RT) are planned. Results: From May-02 to October-06 31 pts were treated (28M, 3F) Age: 55 (32–70) PS 0–1: 6–25. Location: Upper 10, Middle 13, Distal 7, Whole 1. Pathology: Squamous 29, Adenocarcinoma 2. T3/4:14/17 N0/1:8/23 M1a: 3. Weight loss >10 kg 12 pts. 87 cycles have been delivered. Range: 2–4. Mean 2,83. Median 3. Toxicity (episodes): hematological 3/4: no episodes. Emesis 3: 2. Mucositis 3: 2. Asthenia 2/3: 8. 2 pts died in remission due to gastrostomy complications and esophago-tracheal fistula, treatment related. Response: CR 5, PR 9, SD 13, PD 4. Treatment after PTF: Surgery 10 pts (1 upper, 5 middle, 4 distal). 1 distal unresectable at surgery, 2 middle not resected because of liver cirrhosis and liver metastases at surgery. pCR: 1. pPR 6 (R0: 3, R1: 3) Chemoradiation with concomitant Carboplatin: 19, making 3 SD in PR, 2 PR in CR and 1 SD in CR. One PR and 4 SD progressed after chemoradiation. Progression: 21 (local 7, systemic 7, both 7). Died: 19 (16 of disease, 2 of complications of gastrostomy, 1 unrelated) Median PFS: 48,28 weeks (95% CI 32,80 - 63,77). Median OS: 51,14 weeks (95% CI 28,81 - 73,47). Conclusions: This schedule has a good toxicity profile. Surgical rescue is possible in almost a half of middle and distal tumours. Chemoradiation is the best approach for unresectable tumours. Considering stage at diagnosis, survival curves are promising.

No significant financial relationships to disclose.
Repeat 90Y-microsphere radioembolization for hepatic malignancies: Safety and patient selection issues
Authors: Kennedy A. S. , Dezarn W. A. , McNeillie P. , England M. , Overton C. , Sailer S.
Published: March 2020

15177

Background: Liver tolerance to reirradiation with multiple doses of 90Y-microspheres is not known. Many patients (pts) have also received external beam radiotherapy to the liver or through the liver and are surviving long enough to be considered for a second and third liver treatments with internal radiation. Methods: The experience of a single center treating liver tumors with resin 90Y-microspheres was used. Pts that received liver radiation prior to or after resin microsphere therapy were studied. Endpoints were toxicity, tumor response, disease type, latency period between radiation treatments, shunting to lung, and effects on liver volume and function. The delivery activity of microspheres selected was not reduced below that which was typically chosen for patients without prior liver radiation which was 25% reduced from the manufacturer’s BSA dose calculation method. All patients received bilobar microsphere delivery during a single session. Results: A total of 40 pts were identified; 14 women, 26 men, treated 6/2003 to 12/2006, with 35 pts receiving 2 courses and 5 pts with 3 courses of liver radiation. Retreatment with resin microspheres 26 pts, prior external beam radiation in 7 pts, prior glass microspheres in 2pts, prior systemic radiotherapy in 2 pts, and prior stereotactic liver radiation in 1 pt. Liver function was stable and adequate in all patients after additional liver radiation, and no pts developed radiation-induced liver dysfunction (RILD) or veno-occlusive disease (VOD). The percentage of shunting to the lung decreased with retreatment. Tumors treated: 14 carcinoid, 11 colorectal, 6 hepatocellular and cholangiocarcinoma, 2 sarcoma, 3 unknown primary, 1 each of breast, esophagus, and head and neck primaries. Conclusions: Repeated radiation to the liver with 90Y-microspheres appears safe in patients that have sufficient normal liver function and reserve based on known laboratory parameters already used for selection of microsphere therapy. No acute life-threatening, fatal, or late liver damage was observed, i.e. RILD or VOD. No specific dose reduction is recommended for retreatment of the liver.

No significant financial relationships to disclose.
Survival outcomes of advanced pancreatic cancer in an integrative treatment setting: The Cancer Treatment Centers of America experience
Authors: Lis C. G. , Levin R. D. , Neelam R. , Vashi P. G. , Lammersfeld C. A. , Alschuler L. , Grutsch J. F. , Daehler M. , Neelam R. , Granick J. , Gupta D.
Published: March 2020

15188

Background: In this study, we report the survival outcomes of patients with advanced pancreatic cancer who underwent intra- arterial mitomycin/cisplatin therapy at Cancer Treatment Centers of America (CTCA), a community hospital comprehensive cancer center combining conventional and integrative medical therapies. Methods: At our center, all patients undergo a comprehensive program of nutritional, spiritual, physical, naturopathic, and emotional support while receiving an aggressive conventional treatment protocol. Using data collected by the cancer registry, we identified 114 consecutively treated newly diagnosed cases of invasive pancreatic cancer who underwent definitive treatment between Jan 01 and Dec 05. Results: 26 patients were stage III and 88 were stage IV. The median age was 58 years (range 31 to 81 years). 55 patients were selected for intra-arterial therapy with mitomycin/cisplatin. These patients had a PS of 2 or better and either had no metastatic lesions or a single localized liver metastasis. 16 patients in this cohort received radiotherapy. The 59 other patients underwent a variety of therapies. Intra-arterially treated patients had a median survival of 369 days and a 2-year cumulative survival of 19%. Patients not treated with intra-arterial therapy had a median survival of 249 days and a 2-year survival of 11%. Univariate survival analysis found that patients undergoing intra-arterial therapy had significantly better survival outcomes compared to patients undergoing different therapies (Log rank test P = 0.04). The table compares the survival outcomes of recent phase III investigations on first line therapies for pancreatic cancer with those at CTCA. Conclusion: Currently, the published clinical trial data in advanced pancreatic indicates a one-year survival ranging from less than 10% to 28%. Consequently, the survival outcomes of patients undergoing therapy at our center warrant further investigation.

[Table: see text]

No significant financial relationships to disclose.
The validity of complex breast cysts after surgery
Authors: Tea M. M. , Grimm C. , Bikas D. , Kroiss R. , Fink-Retter A. , Kubista E. , Wagner T. M.
Published: March 2020

1519

Objective: Breast cysts are the most common cause of benign breast masses. Simple breast cysts do not need further evaluation, but complex breast cysts require additional assessment due to the potential presence of malignancy. However these complex cysts have rarely been examined and quantified according the associated cancer detection rate. Our study is the first investigation that evaluates the malignancy rate of complex breast cysts identified by histo-pathological results. Material and Methods: Imaging findings of complex cysts were correlated retrospectively with clinical and pathologic outcomes. Results: 150 complex breast cysts were found in 132 women. We detected a high malignancy rate of 14%. Sonographic criteria of a complex cyst such as thick cyst wall (p=0.0006), lobulation (p=0.01) or hyperechogenicity (p=0.04) were predictive of neoplasm. Two or more criteria combined were associated with a 13.6 - fold higher risk of malignancy (p<0.0001). Menopause status, family history or personal history of breast cancer did not influence the detection rate of neoplasm. Conclusion: Based on our results we raise the issue for the need of surgical intervention, compared to observation by ultrasound of complex breast cysts to prevent a missed or delayed diagnosis of breast cancer.

No significant financial relationships to disclose.
Modified-dose capecitabine + bevacizumab for the treatment of advanced/metastatic hepatocellular carcinoma (HCC): A phase II, single-arm study
Authors: Hsu C. , Yang T. , Hsu C. , Toh H. , Epstein R. J. , Hsiao L. , Cheng A.
Published: March 2020

15190

Background: The oral fluoropyrimidine capecitabine (X; Xeloda®) has anti-tumor activity in metastatic colorectal, breast, gastric cancers and HCC. The humanized monoclonal antibody bevacizumab (A; Avastin®) targets VEGF and limits tumor angiogenesis. The combination of X+A is active in breast cancer xenografts and increases the objective response rate (ORR) in patients (pts) with anthracycline- and taxane-resistant breast cancer. X+A also appears to be highly active when administered with irinotecan as first-line treatment for metastatic colorectal cancer. We report data from a multicenter, Ensign’s 3-stage design, open-label phase II trial of X+A as first- line treatment for HCC. Methods: Pts with untreated, histologically confirmed advanced HCC received X 800mg/m2 orally bid d1–14 and A 7.5mg/kg i.v. infusion d1. Treatment was repeated q3w x6 cycles in the absence of disease progression or unacceptable toxicity. Pts without progressive disease after 6 cycles of X+A could continue on the same doses of X+A. Primary endpoint was ORR (RECIST); secondary endpoints were disease control rate, progression-free survival (PFS), overall survival, and safety. Results: 45 patients were enrolled. By Dec 2006 the 25 patients (male, 88%; median age 52 years; Child-Pugh A) enrolled in Stages 1 and 2 of the study had completed at least 6 months’ follow-up and were assessed for efficacy and safety. ORR (CR+PR) was 16% (95% CI 4.5–36.1%) and disease control rate (CR+PR+SD) was 60% (95% CI 38.7–78.9%). Median overall survival was 10.7 months (95% CI, 5.3–14.7) and median PFS was 4.1 months (95% CI, 1.6–6.2); the PFS rate (i.e. the event (PD or death) free rate) at 3 and 6 months was 64% (95% CI 45.2–82.8%) and 34% (95% CI 15.1- 53.2%), respectively. Median number of cycles per patient was 5 (range 1–6). The most common treatment-related grade 3 toxicities included hand-foot syndrome (n=2), nail changes (n=1), diarrhea (n=1), nausea/vomiting/hiccups (n=1), gastric ulcer hemorrhage (n=1). Conclusions: X+A appears to be both effective and well tolerated as first-line treatment for HCC, providing support for further evaluation of this combination in this difficult-to-treat cancer.

No significant financial relationships to disclose.
Impact of risk-reducing oophorectomy on quality of life in women at risk for ovarian cancer
Authors: McArthur H. L. , Hensley M. , Brown C. L. , Chi D. S. , Offit K. , Hurley K. , Li Y. , Gemignani M. L. , Robson M. E. , Barakat R. R.
Published: March 2020

1520

Background: Factors associated with quality of life (QOL) changes after risk-reducing salpingo-oopherectomy (RRSO) have not been clearly defined. We report the results of a prospective QOL study among women undergoing RRSO at the Memorial Sloan-Kettering Cancer Center. Methods: 101 women undergoing RRSO between April 2000 and April 2004 were included. Participants completed questionnaires evaluating perceived risk, symptoms, cancer-related worries/distress, sexual function and QOL at baseline, and at 6 and 12 months after RRSO. All questionnaires were adapted from validated, standardized instruments. Instrument score changes over time were evaluated by GLM repeated measures analysis. Results: The median age of the participants was 48y; 62.4% were post- menopausal; 47.5% had a deleterious BRCA mutation; 46.5% had a family history of OC; 73.3% had a personal history of breast cancer. 74.1% reported a perceived lifetime OC risk =25%. Mean total symptom and depression scores at baseline did not differ by menopausal status, BRCA mutation status, personal breast cancer history or OC family history. Menopausal subscale scores were significantly lower at baseline among pre-menopausal women. Baseline mean anxiety/distress scores and cancer-specific distress scores were significantly higher among mutation carriers than non-carriers. Among women who completed all 3 questionnaires (n=60), overall QOL measured by SF36 did not change over time. There was a significant interaction of menopausal status at surgery with the changes in total symptom and menopause subscale scores. There was a significant interaction between mutation status and post-operative decline in anxiety/distress scores. At 6 and 12 months, 24 (36.4%) and 22 (42.3%) of women, respectively, reported a worsened sex life and approximately 15% were dissatisfied with their decision to undergo RRSO. Conclusions: Most women perceived themselves at increased risk of OC and were satisfied with their decision to undergo RRSO. Mutation carriers demonstrated significant baseline OC-specific anxiety, but experienced a significant reduction post-RRSO. A significant increase in symptomatology was reported after RRSO, particularly among pre-menopausal women; however, there was no significant overall change in QOL.

No significant financial relationships to disclose.
LCIS and tamoxifen use: A single institution review
Authors: Kirstein L. J. , Martei Y. , Roche C. , Smith B. L. , Specht M. C. , Gadd M. A. , Drohan B. , Lawrence C. , Michaelson J. , Hughes K. S.
Published: March 2020

1527

Background: Results of the NSABP-P1 trial were published in 1998 showing a 50% reduction in breast cancer in the high- risk population with the use of tamoxifen. The use of tamoxifen is individualized, and depends on both patient and physician factors. We looked at the recommendations for and the use of tamoxifen in women with LCIS. Methods: A retrospective chart review at a single institution was performed from March 27, 1980 through September 19, 2005 for patients diagnosed with LCIS. Pathology and operative reports, as well as patient notes were reviewed for discussions about tamoxifen. Data was collected on whether a discussion took place, whether tamoxifen was or was not advised, whether the patient declined to take tamoxifen, whether they took it in the past or were currently on tamoxifen. We also examined the rate of DCIS and invasive cancer in this population. Results: There were 321 patients diagnosed with LCIS. Of those patients 193 were diagnosed after the publication of the P1 trial. Of these 193 patients we identified 104(54%) patients whose charts contained notes indicating a discussion about tamoxifen. The results of the discussion about tamoxifen are as follows: 21(20%) patients were currently taking tamoxifen, 16(15%) had taken it in the past, 37(36%) patients declined to take tamoxifen, and 17(16%) had not made a decision about taking tamoxifen. There were 13(13%) patients for whom tamoxifen was advised against. In the entire cohort of 321 patients, 15% went on to develop DCIS or invasive cancer in the first 12 years of follow up. We did not look at cancer rate Vs tamoxifen use due to the small numbers with available information. Conclusions: While the P1 trial recommends tamoxifen for breast cancer prevention in high-risk patients, in our experience, almost half of the patients did not have a documented discussion about the medication, and the majority of those who did decided not to take tamoxifen. This will likely have a large impact on the rate of DCIS and invasive breast cancer in this group.

No significant financial relationships to disclose.
Comparison of weight loss with a National Cancer Institute diet and a plant-based olive oil diet in overweight women with invasive breast cancer
Authors: Flynn M. M.
Published: March 2020

1532

Background: The risk of breast cancer increases with increasing body weight, higher blood levels of fasting insulin and triglycerides, and lower HDL-c. Weightloss and diet can affect these variables. While diets lower in fat are routinely recommended for weightloss and cancer prevention, there is no firm evidence that they have an advantage compared to diets higher in dietary fat. Further, lower-fat diets can adversely affect fasting blood levels of insulin, triglycerides and HDL-c. Methods: Overweight women diagnosed with invasive breast cancer after the age of 50 consumed a National Cancer Institute diet (NCI; total fat: ≥15% to <30%) and a plant-based, olive oil diet (PBOO; total fat: ≥35%, primarily from extra virgin olive oil) for 8 weeks each in a crossover trial with random assignment to order. Fasting blood samples at the end of each diet were analyzed for insulin, triglycerides and HDL-c. Results: Results for 14 subjects. Percent weightloss (NCI: 4.2 ± 2.3; PBOO: 6.2 ± 2.1) in this preliminary group exhibited a significant diet-order effect. Ten of the 14 had lower levels of fasting insulin while on the PBOO diet. Conclusions: These initial results suggest that weightloss can be achieved with a plant-based, higher-fat diet emphasizing extra virgin olive oil, and such a diet may have a metabolic advantage compared to the standard, lower-fat diet.

[Table: see text]

No significant financial relationships to disclose.
Impact of screening on presentation and survival of colorectal cancer
Authors: Beg M. S. , Gupta A. , Komrokji R. , Atiq M. , Ali S. , Safa M.
Published: March 2020

1535

Background: There is an increasing emphasis and utilization of colorectal cancer (CRC) screening. We evaluated the effect of screening on CRC presentation and outcome. Methods: We reviewed all the invasive CRC cases diagnosed between Jan 1995-Dec 2005 at the Cincinnati Veteran’s Affairs hospital. Individual case records were reviewed and the data collected including patient demographics, treatment, outcome, mode of presentation as well as whether CRC was detected as a result of screening. Results: Altogether 288 patients were diagnosed with CRC during the study period. The median age at presentation was 69.3 years and 18.8% were African-Americans. Early stage CRC was diagnosed in 63.4% cases (stage 1: 32.7%, stage 2: 30.8%) and 33.3% were diagnosed at advanced stage (stage 3: 18.1% and stage 4: 15.3%). Seventy seven (26.7%) CRCs were asymptomatic at presentation and were diagnosed as a result of screening. Predominant screening modalities included fecal occult blood testing (46.8%) and flexible sigmoidoscopy (22.1%). The proportion of screen- detected cases increased from 19% in 1995–1999 to 32% in 2000–05 (p = 0.047). Demographics, including age and race, as well as the site of CRC were similar to symptomatic cases. Screen-detected cancers presented early, with 77.9% presenting at early stage (stage 1: 55.8%, stage 2: 22.1%), compared to 51.5% (stage 1: 21.0%, stage 2: 30.5%) of symptomatic cancers (p <0.01). Only 1.3% of screen-detected CRC was found to be metastatic as compared to 21.0% of the symptomatic cases. The screen-detected cancers had significant survival advantage compared to symptomatic cases; with median survival being 81 months vs. 43 months in the latter (p =0.018). A proportional hazard regression analysis indicated that this improvement in survival was related to the fact that screening resulted in earlier stage at diagnosis. Only 20.3% of screen-detected CRC received adjuvant chemotherapy compared to 41.4% of symptomatic cases (p=0.002). Conclusions: An increasing proportion of CRC is being diagnosed as a result of screening. These cancers present at an earlier stage and are associated with a significantly improved survival. However, most CRC still presents symptomatically and more effective population screening is needed.

No significant financial relationships to disclose.
Effects of letrozole on mammographic density (MD) in post-menopausal (PM) women at high risk for breast cancer (BC)
Authors: Andreopoulou E. , Ursin G. , Carapetyan K. , Utate M. , Alvear M. , Rosell M. , Muggia F. , Smith J.
Published: March 2020

1548

Background: Letrozole BC chemoprevention is supported by reductions in contralateral cancer in aromatase inhibitor adjuvant BC trials. Decreased MD may be a surrogate for efficacy in prevention trials. Objective: to evaluate the effects of 12-mo letrozole on MD in PM women at high risk for BC. Methods: 20 healthy PM women had Gail model risk profile and baseline MD prior to letrozole 2.5/d for 1 y. MD was determined by a computer assisted method (Cancer Epidemiol Biomarkers and Prevention 2003;12:332–338) and read blindly (baseline, 6mo films and eventually also 12mo by GU). Health status, lipid profile, bone density, and cognitive function were monitored. Results: by December (<1y): 14 Caucasian, 1 Hispanic, 3 Asians, and 2 Blacks were accrued. The table shows changes in MD at baseline & 6mo in the first 6 women: * reader considered this MD technically unsatisfactory (insufficient contrast). Conclusions: One woman discontinued treatment at 3 mo due to muscle aches. Six and 12mo comparisons will be ready in June 2007. Concordant results and decrease in density are suggested by the available data. Acknowledgements: This work is supported in part by The Lynne Cohen Foundation.

[Table: see text]

[Table: see text]
A phase I trial of nordihydroguareacetic acid (NDGA) in patients with non-metastatic prostate cancer and rising PSA
Authors: Harzstark A. L. , Ryan C. , Diamond M. , Jones J. , Zavodovskaya M. , Maddux B. , Claros C. , Goldfine I. , Small E. J.
Published: March 2020

15500

Background: NDGA is a butanediol with effects on tumor cells, including inhibition of insulin growth factor receptor (IGF-1R) autophosphorylation. In vitro studies suggest that NDGA attenuates androgen-mediated prostate cancer growth without competitive androgen receptor blockade. Its effects on PSA in pts were studied. Methods: Eligible pts included men with recurrent prostate cancer following definitive local therapy with a rising PSA and no metastasis. Both androgen dependent prostate cancer (PSA rising with a normal tesosterone - ADPC) and androgen independent prostate cancer (PSA rising with castrate level of testosterone - AIPC) was allowed. Treatment consisted of continuous oral daily dosing of NDGA according to a planned dose escalation of 750, 1,250, 1,750, 2,250 and 2,500 mg. Pts were followed for safety and changes in PSA and PSA doubling time (PSADT). Results: 15 pts were enrolled: 11 pts with ADPC and 4 pts with AIPC. Median baseline serum PSA was 3.6 ng/mL in ADPC pts and 5.74 mg/mL in AIPC pts. Median age was 66 (range 48–81). Following a median of 5.5 cycles (range 1–13), transaminase elevations occurred in five pts (33%): 1 gr 1, 1 gr 2 and 3 gr 3- all occurring in month 3 or later. Transaminase elevations resolved after drug discontinuation but recurred with repeated dosing. Doses up to 2,500 mg/day were otherwise well- tolerated. The median baseline PSADT was 6.1 months for ADPC and 6.7 months for AIPC and was and 8.4 months on therapy (p=0.12) for ADPC and 4.2 months for AIPC. Of 11 ADPC pts, one (9%) had a decline in PSA by >50% compared to baseline and one (9%) had a decline of 3 fold increase in PSADT while on therapy, one from 11 to 46 months (750 mg), one from 9.5 to 49.5 months (1,750 mg), and one from 5.9 to 46.2 months (2,500 mg). There were no PSA reductions in the AIPC pts, however one pt had a >3 fold increase in PSADT (from 1.4 to 7.5 months). No significant effects on testosterone, adrenal androgen or estradiol levels were observed while on study. Conclusions: NDGA is well tolerated with the exception of transaminase elevations which occur after approximately 3 cycles in a minority of patients. Combined with preclinical data, the modest effects on PSA kinetics suggest that further study on androgen dependent tumors is justified.

No significant financial relationships to disclose.
Phase II trial of the epidermal growth factor receptor (EGFR) inhibitor erlotinib (E) in patients (pts) with advanced papillary renal cell carcinoma (pRCC)—SWOG S0317
Authors: Pan C. , Hussey M. , Lara P. , Mack P. C. , Nagle R. B. , Dutcher J. , Samlowski W. , Clark J. , Crawford E. D. , Gordon M. S.
Published: March 2020

15516

Background: Clear cell RCC often has mutations of the von Hippel-Lindau (vHL) gene and over expression of vascular endothelial growth factor (VEGF). pRCC has mutations of c-met and not vHL. Pre-clinically, normal vHL expression is associated with greater activity of EGFR inhibitors in clear cell RCC (Clin Can Res 6:1518, 2000). PRCC has no effective treatment. Given the absence of vHL mutations we undertook a study of E in pts with pRCC. Methods: Pts with histologically confirmed advanced or metastatic pRCC with measurable disease received E 150 mg PO QD from day 1 to disease progression, pt refusal, unacceptable toxicity, or a delay of therapy >3 wks. Central path review and tissue submission for vHL gene analysis were required. The primary endpoint was response. Further study of this regimen would be considered if the observed response rate (RR) was =20% (i.e. 5+ observed responses). Results: 52 pts from 27 SWOG and 2 ECOG institutions were registered. 7 pts were ineligible (no path submission-3; incorrect histology-1; no measurable disease-2; scans outside timeframe-1). Central path review is ongoing for 7 pts, leaving 39 pts evaluable for response including 30M/9F with a median age of 60.2 y (range 27.9 to 82.3). Median follow-up was 12.8 months (range 1.5 to 35.4 m). 4 pts had confirmed PRs for a RR of 10% (95% CI: 3 - 24%). Five evaluable patients with inadequate response assessment were assumed to be non-responders. Median OS was 26.9 months (95% CI lower limit 12.8 m, upper limit not yet estimable). Probability of freedom from treatment failure at 6 m is 30% (95% CI: 15–45%). There was one Grade 5 adverse event (AE) of pneumonitis thought to be possibly drug-related and one Grade 4 thrombotic AE. 8 pts experienced Grade 3 AEs common to E including rash, anorexia, diarrhea and fatigue. vHL mutation was observed in two patients with stable disease. Conclusions: Though the observed RR in pts with pRCC receiving E is similar to pts with clear cell RCC we did not see enough responses to warrant further study. As this is the first phase II trial reported (to our knowledge) for the subset of pts with pRCC we have demonstrated that less common and distinct histological subtypes can be independently studied in the cooperative group setting.

[Table: see text]
Evaluation of VEGF targeted therapy efficacy in mRCC after sorafenib failure or intolerance
Authors: Hajdenberg J. , Oberoi S. , Cohen N. , Kayaleh O. , Harding D. , Tseng J.
Published: March 2020

15517

Background: Sorafenib, a multi kinase targeted agent with raf and VEGF receptor (VEGF-R) inhibitory properties, has been recently approved for the treatment of metastatic renal cell carcinoma (mRCC). Two other VEGF pathway targeted agents, sunitinib and bevacizumab, have documented efficacy in mRCC. It is not known whether these agents will exhibit biological or clinical activity after prior VEGF directed treatment. Methods: Eligibility applied to patients with mRCC treated with sorafenib within an expanded access program (EAP) at our institution that were later switched to either bevacizumab or sunitinib due to tumor progression or sorafenib intolerance. All patients had measurable disease. Patients were evaluated for response rates (RECIST), treatment duration and progression free survival (PFS). Results: 35 patients that participated in the EAP were identified. 10 patients fulfilled the entry criteria and all of them had clear cell histology. Median age was 66; sex distribution was 70% male-30% female. 6 (60%) received sunitinib and 4 (40%) received bevacizumab. Median treatment duration was 5.5 months (range: 1–15). Of the patients evaluable for response: 5 have SD (50%), 1(10%) had a PR and 1(10%) progressed. 3 are too early to be evaluated. Median PFS was 7 months. Conclusions: Despite the limitations of a small patient sample, the VEGF targeted therapies sunitinib and bevacizumab exhibited a median PFS and reponse rate similar to those reported by other authors as a first line anti-VEGF therapy. Second line anti-angiogenic activity appears to retain efficacy in clear cell mRCC priorly treated with the multi- kinase targeted agent sorafenib. This may provide hypothetical justification for sustained anti-angiogenic therapy after progression. Prospective evaluation of serial and combination approaches is ongoing.

No significant financial relationships to disclose.
Optical coherence tomography guided cystoscopy in diagnosis and management of clinical bladder tumors
Authors: Lee C. S. , Mishail M. , Waltzer W. C. , Liu J. , Wang Z. , Pan Y.
Published: March 2020

15518

Background: Optical coherence tomography (OCT) is a novel tool that permits high-resolution cross-sectional imaging of bladder urothelium during cystoscopy. OCT delineates morphological features of the bladder urothelium, the lamina propria, and the muscularis layer based on their backscattering patterns. We hypothesize that application of microelectromechanical systems (MEMS) mirrors for OCT can improve cross-sectional image resolution of bladder lesions. We report preliminary results from our prospective non-randomized study using MEMS mirror OCT imaging during cystoscopy. Methods: Following our institutional IRB approval, a prospective correlative study was performed evaluating the role of cross-sectional OCT in diagnosis and treatment of bladder cancers. OCT cystoscopy was performed in thirty patients undergoing cystoscopy or transurethral resection for suspected bladder tumors. Any suspicious lesions or tumors seen on cystoscopy were either biopsied or resected as per standard of care. The primary endpoints were patient safety and the correlation between OCT images and histology. Results: Bladder cancer was identified in twenty five patients by pathological evaluation. Twenty four out of twenty five patients were correctly diagnosed with cross-sectional OCT imaging. Four out of five patients with benign lesions were correctly identified. There was one false positive and one false negative in our series. Overall sensitivity and specificity of cross-sectional OCT in diagnosing bladder cancer was 96 and 80%, respectively. There were no complications related to OCT cystoscopy. Axial and lateral resolutions were 10 and 12 microns, respectively. The field of view was measured at 4.5 mm with the depth of penetration measured to be 2 mm. Conclusions: OCT cystoscopy is a promising new tool in diagnosis of bladder cancer. Our preliminary data suggests OCT with MEMS mirrors resulted in high resolution images that may aid in the diagnosis of bladder cancer during cystoscopy. Application of OCT cross sectional imaging may have additional benefits: improved diagnosis, identification of surgical margins, and more complete resection of bladder tumors.

No significant financial relationships to disclose.
Preliminary results of a phase I study: A chimeric monoclonal anti IL-6 antibody CNTO 328 in combination with docetaxel in patients with hormone refractory prostate cancer
Authors: Hudes G. R. , Nanus D. , Qi M. , Prabhakar U. , Corringham R. , Jiao Q. , Eisenberger M.
Published: March 2020

15521

Background: High serum levels of pro-inflammatory cytokine IL-6 may impact the progression and survival of metastatic hormone refractory prostate cancer (HRPC). CNTO328, an anti IL-6 monoclonal antibody, inhibited prostate tumor growth in several preclinical xenograft mouse models. Methods: This Phase 1, open label study evaluates the safety, pharmacokinetics (PK), and pharmacodynamics of CNTO328 at three dose levels (6mg/kg q2 weeks, 9mg/kg q3 weeks and 12mg/kg q3 weeks) in combination with docetaxel (75mg/m2 q3 weeks) in men with metastatic HPRC. C-reactive protein (CRP), a surrogate biomarker of serum IL-6, and circulating tumor cells (CTC) are evaluated. Results: Eight patients with a median baseline PSA value of 56.8 ng/ml (range 13.6- 436.9 ng/ml) were treated in the first cohort (6 mg/kg CNTO328 q2 weeks in combination with docetaxel 75 mg/m2 q3 weeks). At baseline, 6 patients (75%) had detectable CRP and 6 patients had detectable CTCs. The median number of CNTO328 doses and docetaxel cycles administered was 6 (CNTO328: range 3 to 11 doses; docetaxel: range 3 to 13 cycles). No first-cycle DLT was observed for this combination. Three patients discontinued treatment due to docetaxel-related grade 3 adverse events (deep vein thrombosis, hyperbilirubinemia, and nail changes) after 6, 11, and 13 cycles of docetaxel, respectively. Serum CRP decreased to below detectable levels 7 days after the first dose of CNTO328 in all patients with measurable values at baseline and remained undetectable throughout treatment. Two patients with post-treatment CTC values showed CTC reduction from 82 to1, and 127 to1, respectively. Six of 8 patients had = 50% PSA reductions and all had stable or improved bone scans and/or CT scans. PK of CNTO328 and docetaxel, alone and in combination, will be presented. Conclusions: Thus far, anti-IL6 therapy with CNTO328 at 6mg/kg q2 weeks in combination with docetaxel 75mg/m2 q3 week has been feasible and tolerable. Complete suppression of CRP and PSA reduction provide evidence of biological and anti-tumor activity of this approach and support further testing.

[Table: see text]
Prognostic role of chromogranin A expression for docetaxel response in hormone-refractory metastatic prostate cancer
Authors: Gernone A. , Trabucco S. , Troccoli G. , Pagliarulo V. , Pagliarulo A.
Published: March 2020

15528

Background: The neuroendocrine (NE) cells in prostate cancer are indistinguishable from non-NE cancer cells morphologically and are usually detected by immunohistochemical study for NE markers. We analyzed the expression of Chromogranin A (Chr A) in malignant prostate tissue as prognostic factor for docetaxel response in metastatic HRPC. Methods: From January 2003 to December 2006, 40 patients with metastatic HRPC received a median of 12 cycles (range 2–18) of Docetaxel 75 mg/mq every 21 days and 5 mg of prednisone twice daily as initial therapy. Tissue blocks from primary prostate cancer tissues were obtained and immunostaining for Chr A was performed. The median age was 70 years (range 46–82); median baseline PSA: 310 ng/ml (range 0.15–700); median ECOG Performance Status: 1 (range 0- 2). PSA level was measured every 4 weeks and the treatment was considered effective if a rate of PSA-decline > 50% from baseline was found. TTP was the preliminary end point. Results: Response to Docetaxel was assessed at every 3 cycles of treatment. The Chr A expression was found in 19/40 patients with Gleason = 7, PSA < 20, bone and soft tissue metastasis; 10 of them showed PR (decrease in PSA < 50%), 4 SD and TTP was 9.2 months. Moreover they received second line chemotherapy without significant efficacy. 5/19 patients with Chr A expression showed PD, the PSA level was not correlated with clinical outcome, TTP was 5 months and were chemoresistant to different line treatment. Besides, Chr A was not detected in 21/40 patients with Gleason = 7, PSA > 20 and bone metastasis; 10 of them showed CR (PSA normalized) and 11 PR, TTP was 20 months. Conclusions: NE differentiation do not constituite a different histopathological category of prostate cancer but the NE phenotype can be correlated with poorly differentiated adenocarcinoma. NE differentiation can be considered a factor that influences prognosis and treatment in advanced prostate cancer; cases with Chr A expression did not benefit from Docetaxel and had poor prognosis. These preliminary data indicate that initial therapeutic approach should be different according to Chr A expression.

No significant financial relationships to disclose.
Prostate cancer distribution in patients diagnosed by transperineal template-guided saturation biopsy: Implications for brachytherapy treatment planning
Authors: Merrick G. S. , Gutman S. , Adamovich E. , Anderson R. , Allen Z. , Butler W. , Wallner K.
Published: March 2020

15533

Background: Prostate cancer remains undetected in approximately one-third of patients following standard transrectal ultrasound-guided biopsy. In this study, we evaluated prostate cancer incidence, anatomic distribution, Gleason score profile and tumor burden in patients diagnosed by transperineal template-guided saturation biopsy (TTSB). Methods: One hundred and seventeen patients underwent TTSB. TTSB was performed under general anesthesia. All but one patient had undergone at least one prior negative TRUS biopsy. Criteria for inclusion included an elevated PSA and/or the diagnosis of ASAP or high-grade PIN on prior biopsy. The prostate gland was divided into 24 regional biopsy locations with 1–3 biopsies per region. The median number of biopsy cores was 50. Multiple clinical parameters were evaluated as predictors for prostate cancer diagnosis. Results: The mean patient age was 64.8 years with a mean PSA of 9.1 ng/mL and a prostate volume of 78.6 cm3. On average, patients had undergone 2.1 prior negative TRUS biopsies with a mean of 22.4 core biopsies. Prostate cancer was diagnosed in 49 patients (41.9%) with a Gleason score distribution of 6–9. Patients with a prostate volume of = 60 cm3 had a higher rate of cancer diagnosis compared to patients with larger glands (66% vs. 30%). Although no anatomic region of the prostate gland was spared of cancer, there was a preponderance of anterior-based malignancies. In patients with prostate cancer, an average of 9.9 cores were involved. In multivariate analysis, pre-saturation biopsy diagnosis and prostate volume were the best predictors for prostate cancer diagnosis. Conclusions: Transperineal template-guided saturation biopsy diagnosed prostate cancer in 41.9% of previously biopsied patients. Considerable anatomic variability in prostate cancer distribution was documented. Based on this and other reports, cancer eradication will be dependent on treatment of the entire prostate gland.

No significant financial relationships to disclose.
Radiation morbidity and micronuclei in lymphocytes of prostate cancer patients
Authors: Lee T. , Allison R. R. , O’Brien K. F. , Wiley A. L. , Johnke R. M. , Wang W.
Published: March 2020

15540

Background: Since formation of micronuclei (MN) in interphase cells is a reflection of DNA damage, it has been postulated that enhanced peripheral blood lymphocytes (PBL) radiosensitivity might correlate with the development of radiation morbidity. Methods: We conducted the cytokinesis-block (CB) MN assay of PBL in 54 prostate cancer (PC) patients ( mean age ± SEM: 68 ± 1.6 yrs) who had no previous exposure to cytotoxic agents. Patients received standardized pelvic radiotherapy (RT) (41.4 -50.4 Gy) with mean follow-up of 29.1± 3.3 mos. Blood samples were drawn before RT and at designated intervals after RT initiation. Gastrointestinal (GI) and genitourinary (GU) morbidity were determined using RTOG criteria. Results: Average reactors (AR, n = 14) were defined as patients who did not develop morbidity. Grade 1 (G1R, n = 19) and Grade 2 reactors (G2R, n = 21) were defined as those who developed Grade 1 or Grade 2 GI or GU morbidity, respectively. Results of the MN yield in PBL before RT indicated that (1) at baseline level (0 Gy), differences in MN yield for AR, G1R, and G2R patients were insignificant; (2) after ex vivo irradiation (1 - 4 Gy), MN yield followed a linear-quadratic polynomial trend in AR, G1R, and G2R patients; and (3) differences in MN yield in AR vs. G1R or AR vs. G2R patients were significant (P = 0.0001). After the initiation of RT, MN yields in PBL at 24 h, one week, and six weeks, the ratio of relative increment (RI) of RT-induced MN yield, i.e. MNRI = MN (RT-induced) - MN (pre-RT)/ MN (pre-RT) in both G1R and G2R patients was significantly higher than that in AR patients. Our results suggest that prediction of GI or GU morbidity in patients is potentially possible through the evaluation of both ex vivo radiation dose-response relationship of MN in PBL before the initiation of RT and the in vivo MNRI after RT.

No significant financial relationships to disclose.