bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of BRCA 1/2 testing: Body image, sexual functioning, and quality of life (QOL)
Authors: Sun C. C. , Westin S. N. , Lu K. H. , Schmeler K. M. , White K. G. , Daniels M. S. , Arun B. K. , Peterson S. K. , Bodurka D. C.
Published: March 2020

1525

Background: Management strategies for women at high risk of breast and ovarian cancer (OVCA) may affect sensitive QOL issues. Methods: As part of a larger study, 540 women who underwent testing for BRCA 1/2 prior to July 2005 were sent follow- up surveys, including FACT-Endocrine Symptom subscale (FACT-ES), Sexual Activity Questionnaire (SAQ), and a modified Body Image Scale. Chi-square, Mann-Whitney and Kruskal-Wallis tests were used to analyze the data. Results: To date, 309 patients (pts) have responded. Pts with previous oophorectomies were excluded (n=68). The final analysis included 241 pts categorized into 4 groups: Group 1=no breast CA, no prophylactic (proph) surgery (n=39); Group 2=no breast CA, + proph surgery (either proph oophorectomy (PO), proph mastectomy (PM), or PO+PM) (n=20); Group 3= + breast CA, no PO or PM (n=90); and Group 4= + breast CA, + proph surgery (n=92). Median age at time of survey = 50 yrs. Median age at time of PO = 46 yrs. Of 65 BRCA + pts, 36 chose PO, while 32/176 BRCA- pts chose PO (p<.001). 155 pts reported being sexually active at time of survey. Women with PO (n=68) had more endocrine symptoms by the FACT-ES vs pts who chose screening (n=173) (p=.005). Women in Group 2 reported more endocrine symptoms compared to all other women (p=.02). The same trend was noted for sexually active women only (p=.06). There were no differences in activity or pleasure measured by the SAQ between women with PO vs screening; pts with PO reported higher levels of pain/discomfort (p=.04). Women in Group 1 reported the lowest level of pain/discomfort (p=.004) and highest level of pleasure. Higher levels of discomfort and less sexual activity were reported by women with breast CA vs those without breast CA (p<.001; p=.05). Women in Group 3 had the most negative body image while Group 2 had the most positive (p=.03). Women who chose screening reported a more negative body image vs women with PO (p=.01). Pts with breast CA had more negative body image scores than women without breast CA (p=.06). Conclusions: Choice of management strategy and personal hx of breast CA appear to influence sexual functioning, endocrine symptoms and body image in women at high risk of breast and OVCA. Baseline assessment of these factors and continued dialogue are critical aspects of comprehensive care for these women.

No significant financial relationships to disclose.
Eradication of prostatic high grade intraepithelial neoplasia: Hypothesis and clinical proof
Authors: Zweig J. I.
Published: March 2020

1534

Background: Recently normal prostate tissue has been found to contain a high concentration of retinoid X receptors (RXRs), they are found in the highest concentrations in ectodermal tissue. Loss of these receptors is associated with prostatic intraepithelial neoplasia (PIN), and can be present in patients with a normal PSA. There are 115,000 cases of high grade PIN discovered yearly in the United States.The drug bexarotene used to treat cutaneous T cell lymphoma (CTCL). The compound is not a true retinoid in structure, perusal of the structure reveals two aromatic rings one of which contains a carboxy group which would make one anticipate strong hydrogen bonding when it undergoes binding to the RXRs as if it were a retinoid, resulting in “up regulation” of the tissue with increase in differentiation to normal tissue. Based upon this it was felt that it would be fruitful to try bexarotene in High Grade PIN. Method: The diagnosis was based upon 12 biopsies which were done in conjunction with ultrasound localization of the biopsy site, with careful recording of there anatomical position. The patient was started on bexarotene 225 mg per day. The drug was given as a single dose once daily; this dose is 40% of the dose normally used to treat CTCL. The drug was administered for 30 doses During the period of therapy the patient was on Atorvastin T4 total was within the normal range. Results: Four weeks following the last dose of bexarotene the prostate was rebiopsied with 12 biopsies taken. Six of the biopsies were taken from the putative area, the rest in an enlarging target like pattern. The repeat biopsy was negative for the presence of PIN. 14 months later 12 more biopsies were obtained using the same technique, these repeat biopsies were also found to be negative; ie. 24 negative biopsies over 14 months. It is unlikely that the previously involved area was missed. Conclusion: If a mechanism of action were to be formulated, the induction of and increase in RXRs in normal prostate cells would be reasonable. Cells that undergo the formation of PIN, strong hydrogen bonding and inability of those cells to produce more receptors could result in apoptosis. Undoubtedly further study is required to evaluate the effect of this drug in high grade PIN.

No significant financial relationships to disclose.
The histological subtype and grade work as prognostic indicators for platinum-based chemotherapy (CTX) of advanced ovarian carcinoma (AOC)
Authors: Shimizu Y. , Murakami F. , Ogawa N. , Yamada M. , Saskurai S. , Ishiya T. , Katase K. , Hasumi K. , Silverberg S. G.
Published: March 2020

16015

Background: We previously reported the new histopathologic grading system applicable for all histological types of ovarian carcinoma (Cancer 82:893–901, 1998), which thereafter was reappraised by several investigators. The aim of the present study is to investigate the relationship of the histopathologic type and grade with the effect of CTX for AOC. Methods: Between 1/89 and 12/05, 272 consecutive patients (pts) with pT3 (FIGO stage III or IV) AOC pts received 6 cycles or more of cisplatin (70 mg/m2 for 1 cycle)-based CTX combined with aggressive debulking surgery consisting of hysterectomy, bilateral adnectomy, omentectomy, pelvic to paraaortic lymphadenectomy, with or without more extensive surgery including intestinal resections. Histological types and grade were diagnosed according to the WHO classification system and our system reported method, respectively. Results: Of the eligible 261 pts, response was achieved in 67% (CR: 21.8%, PR: 45.2%) of the pts. Response (CR+PR/total) by histological type was 86% (36+91/148) for serous, 97% (16+13/30) for transitional cell, 67% (5+13/27) for endometrioid, 4% (0+1/29) for mucinous, and 0% (0+0/27) for clear cell, respectively. Response (overall/CR) for chemo-sensitive histological types (serous/transitional cell/endometrioid) by grade (G) was 86%/52% for 21 G1, 90%/31% for 64 G2, and 83%/28% for 118 G3 (CR rate: G3 vs G1 + G2: p=0.02). Response duration (CR/PR) by G was not reached/30 months (mo) for G1, 85 mo/23 mo for G2, 40 mo/16 mo for G3. Response (overall/CR) to 2nd line CTX was 75%/38% for G1, 73%/17% for G2, and 47%/10% for G3. Conclusions: Histological type correlated with platinum-CTX sensitivity. CTX regimens should be designed based on the histological subtypes. New “non-platinum” regimens should be considered for both mucinous and clear cell carcinoma. Histological grade worked as an indicator for CR rate, response duration (thus, progression rate), and response rate to 2nd line CTX. Thus, the grade is considered to be a significant prognostic factor for platinum-sensitive AOC.

No significant financial relationships to disclose.
Gestational trophoblastic disease: 25-year experience at the Instituto Nacional de Enfermedades Neoplasicas (INEN)
Authors: Lopez L. Mas , Olivera M. , Casanova L. , Santos C. , Neciosup S. , Gomez H. , Leon J. , Velarde C. , Mariategui J. , Vidaurre T.
Published: March 2020

16031

Background: To evaluate the clinical behavior and results of treatment of gestational trophoblastic disease at INEN between 1980 to 2005. Methods: This is a retrospective analysis of patients with gestational trophoblastic disease, clinical characteristics, results of treatment, toxicity, objective response and survival from January 1980 to December 2005. Descriptive statistics and Kaplan-Meier for survival analysis were performed. Results: Since Jan 1980 to Dec 2005. 595 patients were admitted at INEN; Hydatidiform mole 254 (42.7%) choriocarcinoma 201 (33.8%) invasive mole 41(6.8%). FIGO scoring System, high risk (score >6): 247 (41.5%), low risk (score 1–6): 348 (58.5%). Age ranged from 14 to 54 years, with 255 (44%) cases between 20 to 29 years. The sities of metastasis: lung 67.3%, vaginal 17.9%, brain 8.7%, liver 5.1%. The patients with low risks received treatment with Metotrexate 0.4mg/kg x day x 5 days po, reach disease control with a mean course of 6 (1 - 14), complete remission in 66.1% cases and 97% the overall survival rate to 20 years. Patients with high risk received treatment with: MAC 77 patients, MEC 19 patients, EMACO 48 patients and BEP 14 patients and achieved complete remission in 32.5%, 36.8%, 50% and 25% respectively. On the high risk group we detected two groups according to score > 12 and < 12, with diferent probability of survival at 20 years, for the group with score <12, 80% and the group with score >12, 48%. 98 patients were identified with score >12, and the age of these patients ranged from 15 to 51 years, with a mean age of 36.5 years. The blood B- HCG titers of these patients ranged from 198 to 6710,500. Liver and brain metastasis in 26 cases, number metastasis mayor 8 in 78 cases. Conclusions: Gestational trofhoblastic disease is highly curable. Patients of low risk achieved a 97% overall survival rate to 20 years. There are differences in the overall survival rate between patients of high risk with a score < 12 (80%) and score >12 (48%). This group presented with brain and liver metastasis, and it is important to define the best treatment for this group of patients

No significant financial relationships to disclose.
The role of intensity modulated radiation therapy for locally advanced hypopharyngeal cancer after resection and ileocolic free flap reconstruction
Authors: Hsieh C. H. , Leu Y. S. , Chang Y. F. , Tai H. C. , Huang M. Z. , Hsiao H. T. , Chang Y. C. , Chen Y. J.
Published: March 2020

16521

Background: To estimate the toxicity/efficacy of concurrent chemoradiation therapy (CCRT) and with different modalities for locally advanced hypopharyngeal carcinoma post ileocolic free flap reconstruction (ICFR). Methods: Between April 2003 and December 2006, 15 patients had enrolled and a total of 13 patients were treated for locally advanced hypopharyeal cancer after resection and ICFR. The majority in group was stage IVa and all were squamous cell histology. Five were treated with intensity modulated radiation therapy (IMRT)/chemotherapy (CT) and 8 were treated with the conventional radiotherapy (CRT)/CT, both to a median dose of 64.8 Gy. Two to three cycles of CT given concurrent with RT every 3 or 4 weeks of cisplatin, 15 mg/m2 i.v., D1–5, plus 5-FU, 750 mg/m2 continue infusion, D1–5. Two same regiment of CT had applied monthly after CCRT one month latter for all. Results: The mean survival was 33 months (range, 6–42 months). Two-year actuarial overall survival (OS), disease-free (DFS), locoregional progression-free (LRPF) and distant- metastases-free (DMF) rates of all were 74%, 67%, 83%, 83%, respectively. Comparing the IMRT and CRT group, two-year OS, DFS, LRP and DM rates were 67% vs. 62%, 75% vs. 63%, 75% vs. 87%, 100% vs. 75%, respectively. Except OS rate (p = 0.04), others were not statistically significant. In IMRT group, one left side lower neck failure was noted. In CRT group, one over flap and the other over level III of neck recurrent was noted. Speech ability above 70% in IMRT vs. CRT group were 4/5 (80%) vs. 4/8 (50%). Swallowing with solid diet in IMRT vs. CRT group were 3/5 (60%) vs.3/8 (37.5%). Grade III of dermatitis and mucositis for IMRT vs. CRT group were 40% vs. 100% and 20% vs. 87.5%. The median duration of post surgery to start CCRT and of CCRT were 33 days and 54 days. The interval from post-operation to start CCRT and of CCRT longer than median time would influence LRPF rate (p = 0.05). Conclusions: For locally advanced hypopharyngeal carcinoma post ICFR, IMRT results in lower toxicity, better speech, swallowing ability and superior treatment outcomes when compared with the CRT group. Prolong starting CCRT and extend CCRT time influence LRPF rate.

No significant financial relationships to disclose.
Paucity of economic analyses of phase III clinical trials conducted by the cooperative oncology groups: A review of the evidence
Authors: Fitzner K. , McKoy J. , Bennett C. L.
Published: March 2020

17052

Background: Cancer care is expensive, accounting for $72 billion in direct medical costs. New oncology drugs are frequently costly, and can be > $100,000 per patient. Hence, assessments of the costs and cost-effectiveness of cancer pharmaceuticals alongside phase III clinical trials conducted by the NCI-sponsored cooperative oncology groups represents an important opportunity to generate relevant economic data. Methods: Review of published cost and cost-effectiveness analyses for cancer drugs conducted alongside phase III clinical trials conducted by the NCI-sponsored cooperative clinical trial groups. Results: See Table . Conclusions: Despite increasing concerns over the high costs of cancer pharmaceuticals and the need to evaluate the costs and cost-effectiveness of these agents, NCI sponsored phase III clinical trials rarely include economic assessments. Future phase III clinical trials with expensive new cancer agents conducted by cooperative clinical trials groups should include prospective economic assessments.

[Table: see text]

No significant financial relationships to disclose.
The number of residual metastatic lymph nodes following neoadjuvant chemotherapy predicts disease-free survival in patients with stage III NSCLC
Authors: Kim S. , Cho B. , Moon J. , Choi H. , Shin S. , Sohn J. , Kim J.
Published: March 2020

18024

Background: The prognosis of patients with stage III non-small cell lung cancer (NSCLC) who achieved pathological complete response or downstaging following neoadjuvant chemotherapy is better than those with residual metastatic lymph node (LN). However, the prognostic significance of the number of residual metastatic LNs remains unclear. Methods: From January 2001 to January 2006, 42 consecutive patients with stage IIIAN2 (22 patients) and IIIB without pleural effusion (20 patients) were treated with neoadjuvant chemotherapy. Thirty four of 42 patients were pathologically staged by mediastinoscopy. Neoadjuvant chemotherapy consisted of 3 cycles of platinum based doublet (21 patients with gemcitabine, 15 with paclitaxel, and 6 with docetaxel). Results: After neoadjuvant chemotherapy, pathological complete response and downstaging was achieved in one patient and 24 patients, respectively. No pathological LN metastasis was present in 9 patients (21.4%), and LN metastasis was present in 33 patients (78.6%). With a median follow up of 23 months, the 2-year disease free survival (DFS) rate of patients without residual LN metastasis was statistically better than that of patients with residual LN metastasis (46% and 18% in patients with residual LN, p=0.03). Among 33 patients with residual LN metastasis, age (p=0.01), pathological downstaging (p=0.09) and number of residual metastatic LNs (median 14 months in LN =4 vs median 5 months in LN =5; p=0.01) were significant predictors of DFS in univariate analysis. In multivariate analysis, number of residual metastatic LNs was an independent predictor of DFS among patients with residual LN metastasis, irrespective of pathological downstaging. Conclusions: The number of residual metastatic lymph nodes following neoadjuvant chemotharpy is an independent predictor of DFS in patients with stage III NSCLC.

No significant financial relationships to disclose.
Distinctive characteristics of non-small cell lung cancer in younger patients: A national cancer database (NCDB) analysis of patients under 40 years old (1998–2003)
Authors: Velcheti V. , Goodgame B. , Morgensztern D. , Gao F. , Baggstrom M. , Govindan R.
Published: March 2020

18035

Background: Non-small cell lung cancer (NSCLC) is disease of the elderly and is rare in younger adults. NSCLC in younger patients may be biologically different and have a different presentation and natural history. Methods: We identified in the National Cancer Data Base (NCDB), all patients diagnosed with NSCLC from 1998 to 2003. NCDB is a cancer database maintained by the American College of Surgeons. The NCDB data is obtained from the cancer programs participating in the Commission on Cancer NCDB annual call for data. Data on gender, race, stage and histology were obtained from the NCDB. The characteristics of patients with NSCLC from 16–39 years of age were compared to the entire group. Results: In the NCDB, 551248 patients with NSCLC diagnosed from 1998- 2003 were identified. Of these 4093 were in the age group 16–39. We compared the characteristics of NSCLC in younger group to the entire cohort (Table). Younger patients were more likely to be women, 52% vs 42% (p<0.001), and more likely to present with distant disease (stage 3 & 4) 75% vs 61% (p<0.001). Adenocarcinoma was more common in younger patients, 48% respectively, vs. 38%. Squamous cell carcinoma was far less common in younger patients, 12% vs 28% (p<0.001). Conclusions: Patients with NSCLC who are < 40 years old at diagnosis are more likely to be women and have adenocarcinoma histology. Younger patients present with advanced stage more often than those who are older than 40 years at diagnosis. Table: Characteristics of younger patients with NSCLC

[Table: see text]

No significant financial relationships to disclose.
Retrospective review of DPACE therapy for aggressive, refractory multiple myeloma (MM)
Authors: Gerrie A. S. , Xu W. , Fung S. , Stewart A. K. , Reece D. , Trudel S. , Mikhael J. , Chen C. I.
Published: March 2020

18500

Background: Oral dexamethasone ± thalidomide with a 4-day infusion of cisplatin, doxorubicin, cyclophosphamide, and etoposide (DPACE) is an effective induction therapy prior to transplant in patients (pts) with MM. Limited experience also suggests DPACE may reduce disease burden as a salvage regimen for aggressive, refractory MM. Methods: We performed a retrospective review from 1999- 2005 of all MM pts who received DPACE ± thalidomide as a salvage regimen at our center. Results: A total of 39 pts received DPACE at a median 23 mos from diagnosis (range, 10–84). Median age was 53 years (34–70), 51% stage 3 at diagnosis. Plasma cell leukemia had developed in 12 pts and leptomeningeal disease in 4 pts at time of DPACE. Ten of 24 pts (42%) with cytogenetics had del 13q. Pts were heavily pretreated (median 3 prior regimens; prior autotransplant [ASCT] 38%; thalidomide 64%; and bortezomib 10%). Pts received 1–4 cycles as tolerated for refractory (83%) or relapsed (17%) disease. Thalidomide was used in 41% of cycles. Hematologic toxicity was common (grade 3–4 neutropenia 92% and thrombocytopenia 72%). Although G-CSF was used in 71% of cycles, febrile neutropenia was common (53%) and 26% required hospitalization. Overall RR was 36% (14 pts: PR 12, VGPR 2). An additional 8% achieved MR, 23% SD. PD occurred in 15% and 18% died on therapy (4 progressive MM; 2 neutropenic sepsis, 1 GI bleed). No prior ASCT (p=0.04) and <4 prior regimens (p=0.04) predicted for response to DPACE. Eleven pts proceeded to ASCT and one pt to a clinical trial with lenalidomide with a median OS from DPACE of 24.7 mos (95% CI, 11.2–63.6). Those who did not bridge to transplant or trial (n=27) had a short median PFS of 3.0 months (95% CI, 1.2–5.5) and OS of 6.7 mos (95% CI, 1.8–9.7). OS for all 39 pts was 8.7 mos (95% CI, 6.4–12.4). Conclusion: DPACE may be effective salvage therapy for heavily pretreated MM pts. Although the RR of 36% in this poor prognosis cohort is reasonable, the PFS is short and suggests that the best role for this regimen is in bridging to more definitive therapy such as transplantation.

[Table: see text]
Low-dose dexamethasone and thalidomide with higher frequency zoledronic acid (dtZ) for newly diagnosed multiple myeloma
Authors: Teoh G. , Tan D. , Chuah C. , Hwang W. , Yiu R. , Kuperan P. , Tien S. , Lee L. , Ang A. , Kam G.
Published: March 2020

18506

Background: Although dexamethasone (Dex), thalidomide (Thal) and zoledronic acid (Zol) have frequently been combined for the treatment of multiple myeloma (MM), the ideal dosing schedule is unknown. We previously reported that lower doses of Dex and Thal can be effectively combined with high-frequency dosing of Zol (Haematologica 2005). Methods: This “dtZ” regimen - which comprises weekly Dex 20 mg OM for 4 days, Thal 50 mg ON, and 3-weekly Zol 4 mg - resulted in an impressive response rate (RR) of 61.6% and near complete remission (nCR)/complete remission (CR) rate of 7.7% in 26 patients with relapsed/refractory MM. Results: In this present study, we treated 22 newly diagnosed MM patients with “dtZ” and report an even more impressive RR of 100.0% and nCR/CR rate of 20–35%. The median time to response was 1.8 months and median time to maximum response was 2.2 months. The median time to progression (TTP) has not been achieved yet. As expected, low-dose Dex/Thal resulted in lower (18.1%) grade 3 or 4 toxicities. These were all infections; which lead to further dose-reduction of Dex. There were no thromboembolic events, despite the fact that aspirin was not routinely given. Of particular interest, 3- weekly Zol was not associated with any significant decrease in renal function, and none of our patients developed osteonecrosis of the jaw (ONJ). In fact, at the time of writing of this abstract, more than 1,000 doses of Zol had been administered in a 3-weekly fashion to these as well as other patients, and only 1 patient developed ONJ. This patient who had already received greater than 20 doses of Zol healed uneventfully after receiving appropriate outpatient dental treatment, and subsequently received another 8 doses of Zol with no recurrence of ONJ. Conclusion: In conclusion, the Zol-based “dtZ” regimen is potentially a highly-effective and safe frontline regimen for MM. Using Zol every 3 weeks with lower doses of Dex and Thal does not appear to increase the rate or severity of nephrotoxicity or ONJ. Although we do not know exactly why every patient responded to “dtZ”, we speculate that this could be due to a critical balance that has been achieved between the anti-MM, anti-osteoclastic and immunostimulatory effects of the individual drugs of the combination.

No significant financial relationships to disclose.
First efficacy assessment of a phase II study with cyclophosphamide, vincristine, liposomal doxorubicin, and prednisone plus rituximab, administered every two weeks (R-COMP-14) as primary treatment for NHL
Authors: Herrero J. , Gómez-Codina J. , Provencio M. , Rueda A. , Llanos M. , Lobo F. , Vicente D. , Sabín P. , García-Arroyo F. , Iglesias C.
Published: March 2020

18519

Background: R-CHOP is the standard treatment for CD20+ aggressive B-cell non-Hodgkin lymphoma (DLBCL). Dose dense regimens have shown better outcome and acceptable tolerability compared to standard. Liposomal doxorubicin has demonstrated significant less cardiotoxicity and acute toxicity when compared with standard doxorubicin. The aim of the study is to assess the efficacy and safety of the R- COMP-14 (Myocet™-modified CHOP) in newly diagnosed aggressive DLBCL. Pegfilgrastim was used to provide prophylactic bone marrow support. Methods: Patients (Pts) with stages III, IV or I, II (IPI = 1) were included in this single arm, multicentric, 2-step (Simon design) phase II trial. Treatment: eight biweekly cycles of liposomal doxorubicin 50 mg/m2, cyclophosphamide 750mg/m2, vincristine 1.4 mg/m2 (max. 2mg), rituximab 375 mg/m2 and prednisone 100 mg/d d1–5. Pegfilgrastim was administered on day 2 at standard dose. Interim analysis shows: Twenty-six out of 28 Pts were evaluable for efficacy. Median age: 51 y (28 - 64). Ann Arbor stage: I-II (IPI = 1) 42%, III 29%, IV 29%. Extranodal involvement: 50%. Median basal LVEF was 66% (range 44 - 80). Results: The overall response rate was 84% (CR 64% and PR 20%). Three (12%) Pts had PD and 1 (4%) SD. Median n° cycles was 8 (2-8); the median relative dose intensity per week was 93.5%. Only 4.8% of cycles were delayed and 4.2% of the cycles were administered with dose reduction due to related adverse events. Grade 3–4 neutropenia and thrombocytopenia were observed in 4.0% and 0.6% of cycles respectively. Febrile neutropenia experienced in 3.3% of cycles. Non-hematological G3–4 toxicities per cycles were hepatic (1.7%), emesis (1.2%) and G3 neurotoxicity, asthenia and infection (0.6% each). No other relevant toxicities were observed. Median LVEF after completion of treatment was 63% (range 52 - 76), there was no cardiac clinical event related to the treatment, nor irreversible toxicities. Conclusions: This Interim analysis confirmed the efficacy and safety of the dose-dense regimen in order to continue with the second step of the study. R-COMP-14 treatment with pegfilgrastim bone marrow support warrants further exploration.

No significant financial relationships to disclose.
Safety and efficacy of a triple antiemetic combination with the NK-1 antagonist aprepitant (APR) in high (HEC), moderate (MEC) and high dose chemotherapy (HDC) in multiple day chemotherapy (MDC)
Authors: Jordan K. , Kinitz I. , Behlendorf T. , Sippel C. , Voigt W. , Wolf H. H. , Schmoll H. J.
Published: March 2020

19545

Background: 5-HT3 receptor antagonists (RA) plus dexamethasone (DEX) has been shown to induce 55–57% complete responses from emesis during the 4–5 days of cisplatin chemotherapy. The role of aprepitant in MDC remains to be defined. The antiemetic triple combination of a NK-1-RA, 5-HT3-RA and dexamethasone has not been formally investigated in more than one day chemotherapy. Methods: In this retrospective study, pts. with MDC received APR 125 mg d1, 80 mg consecutive days, granisetron (GRAN) 2 mg daily and DEX 8 mg daily for prevention of acute CINV and APR 80 mg and DEX 8 mg for 2 days for delayed CINV. Endpoints were complete response (CR, no vomiting & no use of rescue therapy) in the acute, delayed and overall phase. Results: Of 103 pts. (f/m 21/82 pts.; median age 40.6y) with various types of cancers 41 pts. (39.8%) received HEC, 44 (42.8%) MEC, and 18 pts. (17.4%) HDC. Median duration of CTX was 3.42 days (HEC 3.9 d). The most frequent regimens were ICE (35%), PEB (14.6%), I3VA (10.7%), MAID (4.9%) and IEV (5.9%). Toxicity: Singultus was reported in 6.8% and loss of appetite in 25.5%. Elevation (CTC grade 1–2) of transaminase/AP/bilirubin and creatinine were seen in comparison to pretreatment values in 15.6%/6.8%/21.1% and 7.8% of all pts.. Efficacy: Acute/delayed/overall CR in HEC was 68.3%/70.7%/63.4%, in MEC 77.3%/84.1%/77.3% and in HDC 77.8%/61.6%/55.6%. Risk factor analysis revealed that pretreatment anxiety increased the risk of vomiting significantly (p= 0.008). Conclusions: Toxicity seems not to be increased by the multiple day treatment of APR (5–7 days) in comparison to the usually used 3-day APR regimen. The CR in the acute and delayed phase in patients receiving HEC was superior to the results reported in the literature with the combination of a 5-HT3 RA and DEX. The CR in the delayed phase in MEC was better than reported by Warr et al. where pts. receiving only one day of MEC and APR mono in the delayed phase. This might be due to the combination of APR/DEX in the delayed phase in our study. These promising results have to be confirmed in a prospective randomized trial.

No significant financial relationships to disclose.
Limited value of routine iron studies prior to initiation of erythropoietin therapy in patients with ovarian cancer
Authors: Riebandt G. , South S. A. , Odunsi K. , Lele S. , Rodabaugh K.
Published: March 2020

19677

Background: Anemia is a common consequence of cancer which significantly impacts patient quality of life. The mainstay of treatment for cancer- and chemotherapy-related anemia is erythropoietin therapy. However, approximately 30% to 50% of patients will not respond to these growth factors. The literature attributes this lack of response to functional iron deficiency, when iron stores are normal but the body cannot meet the increased rate of erythropoiesis. We evaluated the iron status of patients with ovarian malignancies receiving chemotherapy and erythropoietin therapy to establish a baseline for implementation of an intervention service. Methods: After obtaining Institutional Review Board approval, we identified 55 ovarian cancer patients receiving erythropoietin therapy from January to December 2005. We then performed a retrospective chart review for patients who had iron studies available. Results: Thirty-four patients had complete iron studies performed, while an additional 10 had only a ferritin level obtained. The mean hemoglobin for all patients was 9.9g/dl (6.9–13.1) with a mean MCV (mean corpuscular volume) of 92.7fl. Four (12%) patients were iron deficient based on ferritin <100ng/ml and iron saturation <20%. However, these patients had normal MCVs, indicating iron deficiency was not the etiology of their anemia. A few patients were assessed for B12 and folate deficiency, but none were identified. Interestingly, we had 22 patients with elevated ferritin levels (greater than 322ng/ml), with the highest being 2178ng/ml. Conclusions: Our results identified a few patients who were iron deficient, but none were diagnosed with iron deficiency anemia. Therefore, the role of routine iron screening in patients with a normal MCV prior to initiation of erythropoietin therapy is in question. We believe that functional iron deficiency may contribute to anemia in our population. Therefore, we suggest that all patients receive iron supplementation at erythropoietin therapy initiation. We plan to prospectively assess the optimal route of iron administration in ovarian cancer patients in order to improve the response rate to erythropoietic growth factors.

No significant financial relationships to disclose.
A common sense approach to radiation treatment planning of temporal lobe GBM
Authors: Bokstein F. , Kovner F. , Ram Z. , Templehoff H. , Kanner A. A. , Blumenthal D. T. , Corn B.
Published: March 2020

2044

Background: Irradiation remains the cornerstone of management for glioblastoma multiforme (GBM). Guidelines adopted by the RTOG and EORTC advocate encompassing the primary tumor (sometimes with edema), and a 2 cm margin in the high dose volume. These recommendations have emerged from imaging studies and post-mortem analyses. A shortcoming of this approach is the exposure of critical structures (e.g. optic apparatus) to doses of radiation that may exceed organ tolerance. We sought to determine whether the temporal bone (rather than the aforementioned 2 cm radius) serves as a barrier to tumor spread when regarded as the anterior margin for temporal lobe lesions. We hypothesized that toxicity could be reduced without compromising tumor control. Methods: During the period 2003–2006, 250 patients with GBM were treated with surgery and primary irradiation at our institution. Chemotherapy (e.g., Stupp regimen) was given to approximately one-third of patients. 31 patients had lesions confined to the temporal lobe. All patients had MRI at baseline and at monthly intervals following a course of 60 Gy delivered by conformal techniques. The Clinical Target Volume included the primary lesion, the edema when present and a 2 cm margin except in the direction of the temporal bone. At follow-up (median = 10 months), patients were judged to have stable disease, local progression (i.e. failure within the temporal lobe), distant progression (i.e., brain failure beyond the temporal lobe) or combinations of the latter 2. Results: 11 patients have remained with stable disease. 17 have failed locally. 3 have manifested distant failure. Of the latter, only one patient failed in the infratemporal fossa. Conclusions: An acceptable level of recurrence (e.g., <5% beyond the temporal bone) is seen when the temporal bone, rather than a 2 cm margin is employed as the anterior border of the CTV. As GBM patients live longer in the era of combined modality therapy, a greater opportunity will exist to express radiation damage. The strategy proposed herein provides tumor control while respecting optic tolerance without resorting to complex, expensive approaches such as IMRT.

No significant financial relationships to disclose.
Intracerebral microdialysis for determination of the neuropharmacokinetics and neuropharmacodynamics of temozolomide in patients with primary or metastatic brain tumors
Authors: Portnow J. , Badie B. , Xi B. , Liu A. , Hovda D. , Hirt D. , Synold T. W.
Published: March 2020

2074

Background: Microdialysis (MD) is a technique for continuously analyzing concentrations of endogenous chemicals and drugs in the extracellular fluid (ECF) of a body tissue. The purpose of this study is to apply MD to the determination of the neuropharmacokinetics (nPK) and neuropharmacodynamics (nPD) of temozolomide (TMZ) following systemic administration. Methods: After surgical debulking, a MD catheter is placed in peritumoral brain tissue. Artificial cerebrospinal fluid (CSF) is continuously perfused at a rate of 1 μl/min. Fused CT/MRI scans confirm correct placement of the catheter in non-enhancing brain. Starting 24 hrs after surgery, patients are given a dose of TMZ (150 mg/m2), and serial ECF and plasma samples are collected over 24 hrs. TMZ concentrations are determined by LC/MS/MS. In vitro recovery of TMZ via the MD catheter has been determined to be 87±5.5% at a flow rate of 1 μl/min. Prior to and 24 hrs post TMZ, additional ECF samples are collected for analysis of glucose, glutamate, lactate, and pyruvate, which are measured using a CMA 600 Analyzer®. Results: Four patients have been enrolled. There have been no grade 3 or 4 catheter-related adverse events. Mean peak TMZ concentrations in brain ECF and plasma are 0.4±0.2 and 5.5±1.4 μg/ml, respectively. Mean TMZ AUC in brain ECF and plasma are 3.2±1.6 and 18.2±4.6 μg/mLxhr, with an average ECF/plasma AUC ratio of 18±4%. Mean basal levels of glucose, glutamate, lactate, and pyruvate in ECF are 0.4±0.3, 34±66, 3±4, 69±62 mM, respectively. No consistent changes were seen in these nPD markers 24 hrs after TMZ. Conclusions: Concentrations of TMZ in brain ECF obtained by MD are similar to published data of TMZ concentrations in the CSF (Clin Cancer Res 2004;10:3728–36). Baseline values of markers of brain tissue metabolism are consistent with previous data in patients with brain tumors (J Neuro-Oncol 2003; 61:151–60). Intracerebral MD is an important tool that can be applied to nPK/nPD studies of new and targeted agents for the treatment of brain tumors. (Supported by CA01727)

No significant financial relationships to disclose.
Detection of R337H, a germline mutation predisposing to multiple cancers, in asymptomatic women participating in a breast cancer screening programme in southern Brazil
Authors: Palmero E. I. , Caleffi M. , Waddington Achatz M. I. , Martel-Planche G. , Marcel V. , Petroni Ewald I. , Giugliani R. , Schüler-Faccini L. , Hainaut P. , Ashton-Prolla P.
Published: March 2020

21029

Background: A specific germline mutation at codon 337 in TP53 (R337H) has been detected in a number of unrelated subjects with familial cancer risk in South Brazil, suggesting that this mutation may be relatively common in this population. Methods: To assess the TP53 R337H prevalence in a group of asymptomatic individuals unselected for family history of cancer, we studied 750 women aged 40–69 ys participating in a mammographic screening programme in Porto Alegre, Brazil`s southernmost capital. DNA was extracted from peripheral blood using standard procedures and PCR-amplified to generate a 238-base product encompassing TP53 exon 10, which was analyzed by RFLP using the restriction enzyme HhaI. The mutant, uncleaved allele was identified in agarose gels and positive RFLP findings were further confirmed by an independent PCR amplification and bi-directional, automated sequencing. Results and Discussion: The R337H mutant was detected in two of the 750 participants (0.15%), suggesting a much higher prevalence for this than for other TP53 germline mutations causing the LFS/LFL syndromes in the general population. Interestingly, these two subjects reported a familial history of cancer, and were found to be 2nd degree relatives. Three additional family members were also positive: one woman affected with breast cancer at the age of 36 years and two asymptomatic 62- and 80-year-old women. The presence of four R337H-positive cancer- unaffected individuals in this family, two of them well above the age of 50, indicates that this is a low-penetrance allele. In addition, the pedigree does not fulfill any of the currently recognized clinical criteria for the diagnosis of LFS/LFLS syndrome. This is the first study to report detection of a germline TP53 mutation in a population-based screening programme. Conclusions: The TP53 R337H mutant appears to be relatively common and may occur in families that do not fulfill the known clinical criteria for LFS/LFLS, the family described here contains asymptomatic carriers suggesting partial penetrance.

No significant financial relationships to disclose.
Tumor response rate as a function of number of prior therapies in phase II and III trials of topotecan (T) and eniluracil/5FU (EU)
Authors: Ho P. T. , Fleming R. A. , Pandite L. , Lampkin T. A. , Flynn A. A.
Published: March 2020

2501

Background: Patients with 2 or more prior cytotoxic treatment regimens are often excluded from clinical trials because of expectations for greater tumor resistance to treatment. This retrospective cross-study analysis evaluated the relationship between tumor response rate (RR) and the number of prior therapies received. Methods: Phase II and III studies in the GSK database of topotecan (T, n=18) in patients with ovarian or small cell lung carcinoma (SCLC) and of eniluracil/5FU (EU, n=5) in patients with colorectal (CRC) or breast cancer were analyzed. This provided a total 4,220 patients consisting of 1,898 receiving T, 465 receiving various T comparator chemotherapy (paclitaxel, cyclophosphamide, doxorubicin or vincristine), 1,036 receiving EU, and 821 receiving EU comparator (5FU + leucovorin). Number of prior treatments was defined as the sum of all cytotoxic treatment regimens received. Best response was defined according to standard tumor response criteria with missing data or inevaluable assessments considered as progressive disease. Experimental (T or EU) vs. respective comparator arms were combined and an overall RR (CR + PR) in the analysis populations was assessed as a function of the number of prior treatments. Results: The overall RR for ovarian and SCLC patients receiving first-line treatment was 47%. RR declined to 17% for second-line therapy but was unchanged at 18% for those receiving third-line treatment. For all (CRC + breast cancer) patients in EU studies, there were no significant differences between first-, second-, or third-line treatment (RR=12%, 10% and 10% respectively). However, within the limited subset of breast cancer patients (n=145) in EU studies, RR was 54%, 14%, and 11% for first-, second-, and third-line treatments, respectively, suggesting no difference in RR once second-line treatment was administered. Conclusions: The presumption that a higher number of prior regimens always equates with greater treatment resistance may be incorrect. Patients in this analysis with 1 vs. 2 prior therapies exhibit equivalent RR to a broad range of cytotoxic therapies. Exclusion from clinical trials of patients with >1 prior treatment regimen who otherwise meet study eligibility criteria may not be warranted.

No significant financial relationships to disclose.
Immunization of indolent non-Hodgkin’s lymphoma patients with autologous monocyte-derived dendritic cells loaded with heat shocked and killed autologous tumor cells: A phase I study
Authors: Di Nicola M. A. , Carlo-Stella C. , Zappasodi R. , Passoni L. , Liliana D. , Magni M. , Matteucci P. , Mortarini R. , Anichini A. , Gianni A. M.
Published: March 2020

3006

Background: To evaluate the safety and tolerability of vaccination with DCs loaded with killed tumor cells, 18 patients with measurable relapse/refractory follicular (12) and lymphoplasmocytoid (6) lymphoma have been enrolled in a phase I study. Methods: Each patient received at 2-weekly intervals 4 SC injections of 50x10e6 tumor-loaded DCs. Immature DCs were generated by 5-days culture of autologous monocytes in the presence of IL-4 and GM-CSF. Autologous CD19+ tumor cells, harvested from lymph nodes (12) and/or peripheral blood (6), were heat shocked and then irradiated by UVC. DCs were loaded for 48 hrs with killed tumor cells and then were cultured for 12 hrs in the presence of TNF-a. Median prior number of treatment regimens was 2 (range 1–5) comprising 4 patients treated with high-dose chemotherapy. The vaccination was started at least 6-months after the last chemotherapy treatment. Results: All patients were evaluable for toxicity and for efficacy with a median follow-up of 30.5 months (range 18–45 months). Overall, vaccinations were well tolerated and no autoimmune reactions were observed. Mild erythema in the site of injection developed in the majority of patients (12/18), but only in 2 cases induration and extended erythema was observed. Six of 18 patients had objective responses. Three patients had partial responses (PR). One is still in PR and the others have a PR lasting 7 and 15 months, respectively. Three patients had complete remission (CR) and are are still in CR with a mean CR duration of 17 months. The remaining 12 patients had stable disease (8) or progressive disease (4). In the patients in PR, a significant increase of anti autologous tumor-specific T cells, evaluated by ELISPOT assay for IFN-γ, was observed in the post-vaccination lymph nodes, compared to the tissue sample taken before vaccination. In addition, in the responding patients a significant reduction in peripheral blood of FoxP3+ regulatory T cells was observed. Conclusion: The injection of DCs loaded with killed tumor cells is a well-tolerated procedure achieving clinical and immunological responses also in the presence of significant tumor burden.

No significant financial relationships to disclose.
Antigen presenting cell (APC)-targeted hCGβ vaccine for cancer therapy
Authors: Morse M. , Chapman R. , Clay T. , Osada T. , Hobeika A. , Green J. , Davis T. , Keler T.
Published: March 2020

3013

Background: CDX-1307 is a novel vaccine approach designed to target antigens directly into the endocytic compartments of dendritic cells (DCs) and other professional APCs. The β subunit of human chorionic gonadotropin (hCGβ) is selectively over-expressed by a number of epithelial tumors and has been reported to correlate with stage of disease and prognosis. We have coupled this tumor-associated antigen to a human monoclonal antibody (B11) that targets mannose receptors on human dendritic cells and macrophages, and have demonstrated the efficacy of this approach in preclinical models using hCGβ-expressing tumors and cell lines. Methods: In this phase I, dose-escalating study, sequential cohorts of 6 patients with relapsed epithelial tumors receive 4 biweekly intradermal injections of CDX-1307 at either 0.3, 1.0 or 2.5 mg, or 2.5 mg concurrent with GM-CSF. Objectives: safety and tolerability; DLT, humoral and cellular immune response, and clinical activity. Results: Enrollment in the first three cohorts (n=18) is complete with no DLTs. Common potential treatment-related toxicities were injection site reaction (n=5) and fatigue/malaise (n=4), and were generally mild to moderate in severity. One transient Grade 3 generalized allergic reaction in the 1.0 mg cohort was suspected possibly related to either a nut allergy or CDX-1307. One mixed response was seen, with variable effects on circulating hCGβ. CDX-1307 localized to dermal macrophages and DCs in post-treatment biopsies. Conclusions: Administration of CDX-1307 is well tolerated and results in antigen localization in APCs of the skin. Immune Response and tumor impact are under evaluation. Further development includes systemic delivery that may provide antigen targeting to a broad APC population, and combination with immunostimulants to generate optimal immune responses.

No significant financial relationships to disclose.
A phase II clinical study of dendritoma vaccination combined with low dose interleukin-2 in advanced melanoma patients
Authors: Wei Y. C. , Stephenson J. J. , Li J. , Burgin K. E. , Bouton-Verville H. , Jakubchak S. , Holmes L. M. , Meyer K. , Martin J. , Trocha S. D. , Wagner T. E.
Published: March 2020

3051

Background: The use of the fusion product of dendritic cells (DC) and tumor cells as a tumor vaccine represents one of the most promising approaches for cancer immunotherapy. We have developed a novel technology that instantly isolates the hybrids (Dendritomas) from the fusion mixture of DCs and tumor cells and thereby maintains tumor cellular diversity. Animal studies demonstrated that Dendritomas are superior activators of tumor cell specific antitumor immunity compared to fusion mixtures; and phase I clinical studies in advanced melanoma and renal cell carcinoma patients demonstrated that Dendritomas can be safely administered to cancer patients and are able to stimulate immunological and clinical responses in some of the patients. Methods: In order to determine the efficacy of Dendritoma vaccines, we designed a small phase II clinical trial in which individualized Dendritomas are manufactured from and injected into 15 stage IV melanoma patients. In order to boost the antitumor immune responses, a low dose interleukin-2 regime was followed only after the first Dendritoma vaccine. The patients received various numbers of vaccines (1 to 6) at six-week intervals. Clinical responses defined as complete response (CR), partial response (PR), stable disease (SD), mixed response (MR), progressive disease (PD), and no evidence of disease (NED) are monitored. The survival of the patients are monitored as well. Results: Twelve weeks after the first vaccine, three patients were NED; four patients were SD; two patients were PD/MR; and six patients were PD. At the time of the submission of this abstract, two patients were still NED and the median survival was 684 days with twelve of the fifteen patients (80%) surviving more than 431 days and eleven of fifteen patients (73%) surviving more than 519 days. Seven out of fifteen patients (47%) are still alive. Conclusions: The data from this small phase II study demonstrated that Dendritoma therapy combined with low dose IL-2 or other adjuvants may represent an effective therapy for melanoma patients and/or other cancer patients.

No significant financial relationships to disclose.