bluuebunny/crossref_metadata_2025 huggingface dataset:
New molecular breast cancer classification with adjuvant therapy in our population
Authors: Richardet E. , Mascheroni B , Magri I , Perelli L , Cortés M
Published: August 2020

e11624

Background: The molecular classification (Perou) helped to identify new groups of patients with different biological behaviors. A retrospective, descriptive, comparative trial with adjuvant chemotherapy treatment was conducted. Objectives: Analyze the natural history of the subgroups of patients, frequency, site of relapse and Disease-free survival (DFS). Materials and Methods: 200 Medical charts of patients with breast cancer were analyzed from 1997 to 2007, who had received adjuvant treatment without Trastuzumab. The 92, 5 % of Luminal A, 91 % of Luminal B y C, the 75.9 % of Her2 (+) and the 69.2 % of Triple Negative (TN) had received adjuvant therapy with FAC, while 30% of the last two groups were treated with taxanes and anthracyclines. We evaluated the site of the first relapse after adjuvant treatment in relation to the new molecular classification. Log-rank test was used to compare the rates of Disease-free survival (DFS). Results: Frequency: Luminal A (86, 42%) Luminal B y C (65, 33%) Her2 + (33, 17%) TN: (16, 8%) The locoregional relapse in the TN group was 36.4% (P = 0.003), the average of bone relapses were 64.5% on the four groups without statically significance compared to other groups. The CNS had a greater trend in TN groups (16.7%) and Her2+ (13.6%), compared to Luminal Type A-B (0 % y 8.3 %). Disease-free survival (DFS): Luminal A 65.0 ± 5.0 months Luminal B y C 50.3 ± 4.3 months HER2 42.9 ± 5.5 months TN 31.1 ± 7.3 months In the analysis of type A luminal subgroup, a prolonged disease free time was showed when compared with the others subgroups, of major statistical significance Log rank (p = 0.002). Conclusions: Her2 negative and TN tumors have less DFS and a higher locoregional and CNS relapse.

No significant financial relationships to disclose.
Characteristics and behavior of HER-2/neu positive tumors in patients under 35 years of age with breast cancer
Authors: Vigo S. A. , Sansano M. , Marmissolle F. , Mainella A. , Lujan L. , Price P. , Antonelli M. , Mohamed F. , Giacomi N.
Published: August 2020

e11634

Background: Breast cancer (BC) rarely occurs in young women. Presentation, behavior and prognosis of BC in such patients (pts), when compared with older women, are unclear. It is believed that tumor is more aggressive in biologic nature in this group of pts. Objective: to describe Her2/neu status, tumor behavior and prognosis in women aged 35 and under with BC. Methods: We reviewed the records of 45 women aged 35 years or less, with diagnosis of BC between 1999 and 2007. The original Her2 status was analyzed by immunohistochemistry (IHC) with a polyclonal antibody. The results were interpreted using score 0 to 3+. Fluorescence in situ hybridization (FISH) was performed in all samples. Results: Her2/neu overexpression showed up in 8 tumors (17.7%) and all of them were confirmed by FISH. In this group of pts (FISH positive) hormone receptors were positive in 50%. Stage at diagnosis was I 2 pts and II 6 pts. 5 out of the 8 pts with Her2/neu tumors had axillary node involvement (11.1% out of the total of population), and tumor size was more than 2cm at diagnosis. All of them were invasive ductal carcinoma. Postoperative radiotherapy was given to 6pts while all pts with Her2/neu positive tumors received chemotherapy with anthracyclines, taxanes and trastuzumab. Disease free survival of 24 month was achieved in 5pts, 1pt died with bone, lung and liver metastases. 2pts had progressive disease (bone and lung metastases one of them, and local recurrence the other one). Conclusions: In our population of pts, 17.7% were Her 2/neu positive. In this small group of pts lymph node involvement was frequent and tumor size was more than 2cm. Progressive disease with distant metastases in bone, lung and liver was observed. Despite of these negative characteristics 5 out of 8 pts (62.5%) had DFS of 2 years.

No significant financial relationships to disclose.
Phase IIb double-blind, randomized, placebo-controlled trials for the efficacy and safety of sorafenib in patients (pts) with metastatic or locally advanced breast cancer (BC): Review of the Trials to Investigate the Effects of Sorafenib in BC (TIES) program
Authors: Baselga J. , Gianni L. , Gradishar W. J. , Hudis C. , Perez E. A. , Piccart-Gebhart M. , Schwartzberg L. S. , Sledge G. , Fleming T. R.
Published: August 2020

e12000

Sorafenib is a potent multikinase inhibitor approved by the FDA and EMEA for the treatment of advanced renal cell carcinoma and hepatocellular carcinoma. As a single agent, sorafenib has been shown to have activity in pts with BC. Here, we review the TIES program, a compilation of currently ongoing investigator-sponsored phase IIb multinational, randomized, double-blind, placebo-controlled studies that aim to determine the optimal sequencing of pharmacologic agents for the treatment of BC. All studies will combine sorafenib with first- and/or second-line chemotherapy and/or hormonal therapy in pts with HER2-negative metastatic or locally advanced BC, enroll 220 pts, stratify pts by visceral vs nonvisceral disease, allow pts with evaluable and measurable disease, and include pts with treated brain metastases. The primary endpoint of all trials will be progression-free survival. Secondary endpoints will be safety, overall survival, objective response rate, duration of response, and time to progression. Some studies will also assess quality of life, pharmacokinetic sampling, and biomarkers. Additional information on four of the trials is shown below (Table). Patient characteristics and accruals will be reported.

[Table: see text]

No significant financial relationships to disclose.
Metastatic male breast cancer (mMBC): Prognosis and survival of 35 patients
Authors: Foerster R. , Foerster F. G. , Baaske D. , Schubotz B. , Wulff V. , Rudlowski C.
Published: August 2020

e12001

Background: Only about 1% of breast cancers occur in men, respectively 400–500 new cases per year in Germany. Clinical studies on breast cancer in men are limited for case studies or retrospective analysis. In the recent years no studies have been published on the clinical course of mMBC. Therefore we here present a retrospective cohort study on this topic. Methods: Clinical and pathological tumor characteristics and the follow-up of male breast cancer patients with metastatic disease diagnosed in the region Chemnitz/Zwickau in the state of Saxony between 1995 and 2007 were documented and statistically evaluated. Results: 35 men (median age 64.7 years) were diagnosed with mMBC; 10 (28.6%) of them with primary metastasis. Median survival time: 37 months. 85.7% (n = 30) had an invasive-ductile carcinoma. Most common localizations of metastasis: bones (n = 19), lungs (n = 19), liver (n = 7). Tumor characteristics at the point of diagnosis: 63.9% (n = 22) T2-T4, 38.7% (n = 12) G3, 48.4% (n = 15) N+, 79.3% (n = 23) ER+, 72.4% (n = 21) PgR+, 12.5% (n = 3) HER-2+, 13.8% (n = 4) triple negatives, and 69.2% (n = 9) AR+. The therapy in the metastatic state was very heterogeneous and consisted of systemic endocrine therapy in 45.5% (n = 10), systemic chemo therapy in 9% (n = 2) or a combination of both in 45.5% (n = 10). In 14 (40%) cases a palliative radio therapy was administered. The initial tumor characteristics like tumor size, nodal state and grading were not of any prognostic relevance on a future development of metastasis. Prognostic unfortunate were a negative hormone receptor state (p < 0.001) and triple negative receptor state (n.s.). Patients with primary metastasis showed a tendency towards worse survival than patients who developed the metastasis during follow up (n.s.). If a systemic therapy was given the prognosis was significantly improved (p < 0.005). Conclusions: Patients suffering from metastatic male breast cancer had a comparatively good prognosis and showed significant benefit from systemic therapy in this study. In patients with negative receptor state and without systemic therapy the prognosis was especially worsened. Our data suggest that an up-to-date adequate systemic therapy is capable of improving survival in men with metastatic breast cancer.

No significant financial relationships to disclose.
Patterns of metastatic (met) disease sites in breast cancer (BrCa): Implications for availability of fresh tumor tissue (FTT) for personalized BrCa treatment (Rx) planning (TP) in met disease
Authors: Presant C. A. , Bosserman L. , Howard F. , Emilio B.
Published: August 2020

e12004

Background: Personalized Rx for patients (PTs) can improve response. Although archival tissue is available in all PTs, FTT testing of molecular, immunohistochemical, and/or chemosensitivity characteristics may be more optimal for TP than tissues obtained before previous Rx and/or new mets, and archival tissue is inadequate for cell culture information. This study was performed to determine the availability of FTT in a multi-site cancer center. Methods: Pts seen over 22 months were evaluated. PT clinical characteristics were evaluated to determine the prevalence of mets by site, and feasibility of biopsy (bx) for FTT by site. A bx algorithm for FTT was developed and quantified. Results: 26,794 successive PTs were evaluated. BrCa was present in 2043 (7.6%). Median age was 61 (range 27 to 98). Mets were present in only 174 (8.5% of BrCa) who had 256 sites involved (1.47 site per PT). 68% of PTs had multiple sites involved. Of PTs with multiple sites, 96 (81%) had 2, 16 (14%) had 3, and 6 (5%) had 4 sites involved. Single site was the pattern in only 9% of liver, 7% of lung, 32% of bone, 0% of adrenal 6% of skin, but 71% of brain mets. The most frequent sites of mets were bone (50%), lung (31%), liver (26%), brain (10%), skin or soft tissue (11%), lymph node (6%), and effusion/ascites (3.4%). In order to theoretically obtain FTT for development of a personalized TP based on an algorithm preferring in order local bx > para/thoracentesis, > non-osseous needle bx > video-assisted tissue bx > osseous bx, 18% of PTs would have had a local bx, 3% para/thoracentesis, 23% liver bx, 19% lung bx, 17% bone bx, and 12% would not have had a bx because of brain-only mets. Conclusions: Most BrCa PTs in oncology practices have only locoregional disease. Most PTs with mets have multiple sites. FTT acquisition would be feasible for 88% of PTs with mets for personalized TP, and in most the bx would be simple and non-invasive. However, tissue culture tests would necessitate a more invasive video-assisted bx in 42% of PTs. Physicians should consider additional bx to personalize TP when appropriate for improving outcomes.

[Table: see text]
HER-2 gene amplification in circulating tumor cells (CTCs): Concordance with amplification status in primary breast cancers and metastatic lesions
Authors: Yerushalmi R. , Mishaeli M. , Huntsman D. G. , Gelmon K. A.
Published: August 2020

e12006

Background: Recent studies have suggested a significant incidence (10%-30%) of discordance in HER-2 expression between metastatic lesions and the primary breast cancer (BC) which can result in inappropriate treatment recommendations. Biopsies of recurrent BC can aid in determining the expression but are often painful, costly, or cause delays in therapy. We initiated a study with the objective to determine and compare the molecular characteristics of the primary tumor, CTCs and metastases to assess whether the assessment of HER-2 gene amplification status in CTCs by FISH analysis could be used to determine treatment. Methods: After consent, patients with metastatic BC were enrolled, peripheral blood was collected (5 cc-10 cc), metastases were biopsied and HER-2 expression was determined. Blood samples were used for the CTC assay. We performed the CTC enrichment assay using a combination of anti CK and anti-EpCAM. The criteria for CTCs were: positive for cytokeratins 8, 18, 19, positive for DAPI and negative for CD45. Slides were scanned for CTCs using the Ariol system. When a CTC was identified the slide was reused for HER-2 FISH staining using the PathVysion HER-2 DNA Probe Kit. Initial attempts of FISH on CTCs took 48 hours to complete; to hasten the process, the second scan for FISH was done only on selected areas and the images for CTCs and FISH analysis were fused to obtain FISH images on a specific CTCs resulting in a 1 hour process. Results: To date 58 samples were collected, 40 of which had CTCs. At present, biopsies are being assessed and compared to the primary lesion in the initial 20 cases. Conclusions: FISH analysis of CTCs is a feasible technique and may be used to assess the specific molecular characteristics of breast cancer. Whether their HER-2 status reflects the metastatic or primary tumor is still unclear but is being determined and may have useful clinical application.

No significant financial relationships to disclose.
Circulating tumor cells (CTC), [18F]fluorodeoxyglucose positron emission tomography, and computed tomography (PET/CT) for treatment monitoring in patients with metastatic breast cancer (MBC)
Authors: Tamkus D. , Chandana S. R. , Berger K. , Aung T.
Published: August 2020

e12007

Background: Use of [18F]-fluorodeoxyglucose PET /CT and/or CTC is being investigated to follow up response to treatment in patients with MBC. It is not clear if these tests can be a surrogate for one another. Methods: We retrospectively analyzed a database of female patients with MBC undergoing chemotherapy or hormonal therapy. Most of these patients received at least 2 lines of therapy. Standard CT scan tumor measurements were used to assess response to therapy. CTC were defined either low (0–5) or high (>5). Maximum standard uptake values (max SUV) on PET scan were defined either low (<3) or high (>3). Correlation between the max SUV and CTC counts was statistically analyzed. Sensitivity, specificity, positive and negative predictive values were calculated from 2 x 2 table. Results: A total of 9 female patients with MBC were identified (mean age of 52 years). The receptor status of these patients includes 67 % positive for ER and 33 % positive for HER-2/neu. Median follow up was 9.8 months. There were 59 time points (> or = 4 weeks apart) when either PET/CT or CTC were performed. The results of PET/CT scans were compared with CTC at 38 events. The sensitivity of CTC to detect metastatic disease shown on PET/CT was 32% and specificity of 100%. The positive and negative predictive values were 100% and 32% respectively. There was a positive correlation between the max SUV and CTC count (p = 0.001). However in three patients, despite of progression of disease per PET/CT, CTC were undetectable at three different time points. Interestingly, two out of these three patients were triple negative. Disease progression was confirmed by biopsy in two of these patients. Conclusions: Our data suggest positive correlation between PET/CT scan and CTC. However, CTC had poor sensitivity and negative predictive value to detect progressive metastatic disease. Normal CTC values have to be interpreted cautiously in patients with MBC. We are now planning to investigate the utility of these tests, prospectively, in a large cohort of MBC patients.

No significant financial relationships to disclose.
First-line trastuzumab utilization: Patterns of care and progression in the community setting
Authors: Gruschkus S. K. , Shankleton J. A. , Brammer M. , Forsyth M. , Lalla D.
Published: August 2020

e12009

Background: This study describes patterns of care and outcomes in metastatic breast cancer (MBC) patients treated with trastuzumab (T) within the US Oncology network. Methods: This retrospective study utilized data from US Oncology's iKnowMed EMR system. HER-2 (+) MBC patients who initiated a first-line regimen containing T between January 1, 2006 and July 31, 2007, were identified. Patients were divided into three treatment cohorts: A) those who discontinued T prior to disease progression; B) those who continued T following discontinuation of chemotherapy prior to progression; and C) those who received T monotherapy. Patients were followed through October 31, 2008, to measure treatment duration and observe progression (as defined as escalation to second-line therapy). The Kaplan Meier method/log-rank test were used to estimate and compare progression free survival (PFS) across cohorts. Results: We identified 139 patients receiving first-line therapy including T. The median age was 58 years and 84 patients were ER and/or PR (+). The top 5 chemotherapy regimens included T plus: paclitaxel (n = 14); docetaxel (n = 14); vinorelbine (n = 14); carboplatin/paclitaxel (n = 12); carboplatin/docetaxel (n = 7 pts). Twenty-one (15%) patients were in cohort A, 55 (40%) were in cohort B, and 63 (45%) were in cohort C. Overall, the median duration of first-line T use was 281 days (mean = 287; range = 1–862). Following the initiation of first-line therapy, a total of 56 (40%) patients progressed (median follow up = 15 months). Following progression, 22 (39%) patients received second-line regimens containing T. The overall median PFS was 17.4 months (mean = 18.6). Patients in cohort A (n = 15) had significantly shorter PFS versus patients in cohort B/C (median 3.9 and 19.6 months, respectively; p < 0.001). Conclusions: In this observational study within the outpatient community setting, persistent first-line T use for MBC was associated with delayed disease progression. Future research should evaluate the causal relationship of this association. In addition, a more comprehensive evaluation should be conducted of therapies prescribed concomitant to T for patients treated with T “monotherapy.”

[Table: see text]
Allogeneic stem cell immunotherapy for advanced metastatic breast cancer
Authors: El Cheikh J. , Goncalves A. , Esterni B. , Furst S. , Faucher C. , Chabannon C. , Gravis G. , Extra J. , Viens P. , Blaise D.
Published: August 2020

e12012

Background: Despite continuous progress, advanced breast cancer (ABC) remains an incurable disease. Immunotherapy using allogeneic stem cell transplantation (ASCT) has been proven successful in malignant hematological diseases. We have investigated ASCT as a possible way of improving tumor control in ABC. Methods: Between 1998 and 2008, 21 ABC pts underwent ASCT after the same reduced intensity conditioning (RIC) based on fludarabine, busulfan and ATG or low dose irradiation from a HLA-identical sibling. Results: Pre-treatment characteristics of pts receiving ASCT were the following: ER or PR +, 79%; HER-2+, 27%; liver metastasis, 48%; adjuvant chemotherapy, 90%; median number of metastatic sites, 2 (1–4); 95% have received anthracyclines and/or taxanes; 71% have received endocrine therapy; 48% received more than 2 lines of cytotoxics; median age at transplant was 39 years (range 22–57). At time of transplant, 48% pts had progressive disease (PD), and 52% pts had a stable disease (SD). All pts engrafted and none died from transplant related mortality. While outcome was uniformly poor for pts with PD (no response and no surviving pt at 2 years), pts with SD achieved a 36% response rate (p = 0.09) and a 55% (CI95%, 28–79%) overall survival (OS) probability at 2 years (p = 0.001). To better assess the impact of ASCT, we looked for control group. During the same period, a total of 93 pts were searched for a HLA match sibling: 41 pts had an identified donor while 52 had no donor (group A). Of those 41 pts with a donor, 21 proceeded to transplant (group C) and 20 did not (group B). Reasons for not proceeding to transplant when a donor was found were: disease progression: 12 pts; patient decision: 6 pts; referring MD decision: 2pts. Progression-free survivals (PFS) were assessed from the first day of the last therapy immediately preceding HLA typing. Median PFS were 7.4 (CI95%, 6.2–12.4), 5.7 (CI95%, 4.6–12.8), and 18.2 (CI95%, 12.9–30.7) months for groups A, B, and C, respectively and were strikingly different between the 3 groups (p = 0.014). OS were not different. Conclusions: ASCT can be safely performed in ABC and may provide an outcome advantage to selected pts deserving further investigations.

No significant financial relationships to disclose.
French experience of patient management when receiving oral vinorelbine chemotherapy (NVBO) for metastatic breast cancer: Final results of a prospective observational survey on practices
Authors: Lotz J. , Husseini F. , Finck M. , Rotarski M. , Bastit L. , Riviere A. , Youssef A. , Mouysset J. , Nahon S. , Piolat V.
Published: August 2020

e12013

Background: An observatory on practices has been implemented in France with the aim of investigating the correlation between patient (pt) profile and the use of an oral chemotherapy (OCT), NVBO. Methods and Materials: Three questionnaires were used: a “Physician” questionnaire (medical practice conditions, role of OCT), a “Patient” questionnaire (pt disease history, prescription selection factors and compliance), and a Patient Preference self-questionnaire (partly based on the EORTC QLQ-BR23). Results: Between February 06 and February 08,355 pts were enrolled in 47 centers. Breast tumours were classified as having limited aggressiveness with or without visceral metastasis (41.2%) or slowly progressing visceral metastasis and DFI>24 months (42.3%) or aggressive disease with visceral metastasis and DFI<12 months (16.5%). Pts had previously received hormonotherapy in 72.4%, iv CT in 78.6% and OCT in 31%. NVBO was prescribed as monotherapy in 53,6% and association in 46,4%, with iv in 35% (66.7% with trastuzumab), with oral in 65% ( 97.2% with capecitabine ). 86.2% of pts preferred OCT for 3 main reasons : more time with their family, social life maintained and treatment at home. Physicians’ major parameters of OCT choice according to score (1 to 4) were : patient-related factors (QOL 3.61), reduced hospital stays (2.99) and problems related to venous administration (2.62). Conclusion: NVBO brings added value in terms of pt convenience allowing improved QOL and reduced hospital stays while keeping optimal compliance to treatment schedule.

[Table: see text]
CA 125 in the early detection of metastatic breast cancer
Authors: Ertl I. , Heinemann V. , Laessig D. , Nagel D. , Seidel D. , Stieber P.
Published: August 2020

e12015

Background: Kinetics of CA 15–3 and CEA have a high specificity in the early detection (= asymptomatic patients) of metastatic breast cancer disease. However, this high specificity is associated with a lack of sensitivity (false-negative results). To decrease the number of false negative (FN) patients, the additional diagnostic potential of CA 125 kinetics was evaluated. Methods: We analysed 1,011 follow-up samples of 95 patients. Forty-seven of these patients showed metastatic recurrence during follow-up. Based on analyses, published previously, a reproducible increase of CA 125, CA 15–3, or CEA ≥100% based on the individual baseline value of each patient was selected as a reliable indicator for metastatic disease. Results: None of the 48 patients with NED had a reproducible increase of either CEA, CA 15–3, or CA125, i.e., all three tumor markers reached a specificity of 100%. At the time of first metastatic disease, the overall sensitivity was 29.8% for CA 125, 44.7% for CA 15–3, and 21.3% for CEA. In 7 patients (14.9%) only CA 125, in 14 patients (29.8%) only CA 15–3 and in 6 patients (12.8%) only CEA increased. In 8 patients (17.0%) more than one marker increased. The sensitivity of the CA 15–3/CEA combination was 59.6% (95%-CI: 45.5%-73.6%). With the additional use of CA 125, the sensitivity could be increased by 14.9% to 74.5% (95%-CI: 62.0–86.9%). The sensitivity of the marker combination was 66.6% for metastases in one site (n = 33) and 100% for metastases in more than one site (n = 14). Conclusions: This retrospective analysis indicates that CA 125 increased the sensitivity of the CA 15–3/CEA combination by 14.9% without loss of specificity. The combined use of CA15–3/CEA/CA125 may therefore be helpful for early detection of metastatic disease. The usefulness of this approach is presently verified in a prospective trial.

[Table: see text]
Prelimenary results of a phase I/II of a combination of cetuximab and taxane for triple negative breast cancer patients
Authors: Nechushtan H. , Steinberg H. , Peretz T.
Published: August 2020

e12018

Background: The triple negative subtype of breast cancer is currently only treated with chemotherapeutic agents. It has been demonstrated that over 50% of this kind of tumors express EGFR (HER-1). Cetuximab is a humanized antiEGFR IgG1 antibody. In colon cancer there are also high percentage of EGFR expression and addition of Cetuximab to chemotherapy results in renewed sensitivity to treatments. We therefore hypothesized that in a similar manner addition of Cetuximab to taxanes which are among the most potent anti breast cancer drugs will result in increased effectiveness in this subset of breast cancer patients. Methods: From January 2007 to January 2009, we treated 12 breast cancer patients with either paclitaxel 80 mg/m2, (10 patients) or docetaxel (30 mg mg/m2) (2 patients), with cetuximab weekly. Patients had a pathology sample of breast cancer with triple negative components, metastatic disease and up to two prior chemotherapy lines in the metastatic settings. Results: Patient characteristics (median): age 60 (31–69) years, prior taxane therapy 9/12 pts. Toxicity: Dermatologic grade 2 9/12 grade 3 3/12, nail disease grade 2 10/12 evaluable patients. One patient developed severe swallowing difficulties after 19 month of therapy which may or may not be linked to the treatment. Response is evaluable for 11/12 patients. Response which includes clinical response, tumor marker decrease, and a metastasis size decrease was noted in 9/11 patients. Including tumor marker normalization and nearly a roentgoenolgic CR in a young patient previously treated with several chemeotherapietic lines. Three patients developed brain metastasis during treatments. Molecular pathology is now performed. We continue accrual. Conclusions: Administration of taxane-cetuximab weekly therapy for triple negative breast cancer patients is possible. Toxicity is the cumulated expected toxicity of each of the agents — special care should be taken for nail disease which occurred in most of the patients. Some impressive clinical responses were obtained even in taxane pretreated patients.

[Table: see text]
Capecitabine (X) in the routine treatment of advanced breast cancer (BC): Results from a large (n = 870) noninterventional study
Authors: Schoenegg W.
Published: August 2020

e12021

Background: This observational study evaluated patient (pt) characteristics, treatment schedule and setting, efficacy and tolerability of X in routine clinical practice in Germany. Methods: Pts with advanced BC pretreated with or ineligible for anthracycline-containing therapy received X. As there was no specific protocol for X administration, data on dose, treatment duration, treatment delays/interruptions, and concomitant anticancer therapy were collected as well as efficacy data. Pts were followed until disease progression or completion of 12 cycles (with long-term follow-up in pts who were progression-free after 12 cycles). Results: Between 2002 and 2007, 870 pts were recruited from 135 centers, of whom 846 were eligible. Most pts (62%) were aged 50–69 years and 64% had received prior taxane therapy. X was given as monotherapy in 64% (median starting dose 1070 mg/m2 bid) and combination chemotherapy in 36% (median starting dose 987 mg/m2 bid), typically with vinorelbine or docetaxel. Generally, pts receiving X alone were slightly older and were more likely to have hormone receptor-positive disease than those receiving combination therapy. 35% of pts received X as first-line therapy. Pts received a median of 7 cycles; 26% received ≥12 cycles. Overall response rate (RR) was 41% (95% CI: 38–45) and median progression-free survival (PFS) was 7.5 months (95% CI: 7.1–8.3). RR was higher with combination therapy (49%) than monotherapy (37%), but PFS was similar in the two subgroups. Good performance status at baseline was a significant predictor of efficacy. The most common non-hematologic adverse event was hand-foot syndrome (all grades: 54%; grade 3: 7%), leading to premature treatment discontinuation in 6%. Myelosuppression and alopecia were substantially less common when X was administered as monotherapy than as combination chemotherapy. Conclusions: X, either alone or in combination, is a feasible and effective treatment for advanced BC. Our findings in real-life clinical practice compare favorably with results from interventional studies, perhaps reflecting the longer treatment duration possible at a more tolerable dose.

No significant financial relationships to disclose.
Peritoneal disease in breast cancer: A specific entity with an extremely poor prognosis
Authors: Tuthill M. H. , Pell R. , Giuliani R. , Adrian L. , Lewis J. S. , Leonard R. , Coombes C. , Stebbing J.
Published: August 2020

e12023

Background: We are observing increasing numbers of patients with advanced breast cancer and peritoneal metastases. There are few published data regarding the prognosis, clinical characteristics, and management of such individuals. Methods: The electronic imaging database at Charing Cross Hospital was searched for the terms ’breast,’ ’cancer or tumor,’ ’peritoneal,’ and ’ascites’ from 2000–2008. Those with confirmed peritoneal disease from breast cancer, as described on ultrasound or staging CT reports with a clinico-pathologic confirmed diagnosis, were included in the study. Results: A total of 1,628 scans were screened and initially 168 patients were identified. A subsequent total of 44 individuals (2.7% of the metastatic cohort) were included in this study, as having breast cancer with peritoneal secondaries. Of these, the majority (77%) had invasive ductal carcinomas (IDC). While the median survival from the diagnosis of metastatic breast cancer measured 20.5 months (range 0.1 -125 months), the median survival of patients with peritoneal disease was 1.56 months (range 0.2 - 27 months). Conclusions: Our data shows that the median survival of patients with peritoneal breast cancer metastasis is surprisingly poor, with only a minority surviving more than six months. A specific association with invasive lobular carcinoma (ILC) was not observed. The dismal outcome of these individuals despite further active therapy merits their inclusion into trials of new treatments.

No significant financial relationships to disclose.
Hormonal changes with anastrozole treatment in breast cancer
Authors: Ali S. , Ali M. F. , Mundia M. , Mundia A. G.
Published: August 2020

e12026

Background: Aromatase inhibitors are a class of drugs that inhibit tumor growth in hormone receptor positive breast cancer, in postmenopausal women. They inhibit the conversion of androgens to estrogens. Both clinical benefit and side effects are believed to be due to alterations in blood hormonal levels. Methods: Clinical charts of postmenopausal women with estrogen receptor positive breast cancer, receiving anastrozole 1 mg daily, were reviewed to determine the clinical side effects and blood hormonal changes during treatments, at a community oncology practice. Hormonal levels measured were serum testosterone, serum estrogens and prolactin levels. Results: There were 31 postmenopausal women age 52–73 (median 62) years, receiving anastrozole 1 mg daily. Duration of treatment was 8 to 42 (median 24) months. Clinical side effects noted were joint pains in 4 patients; mild to moderate hot flashes in 4; temporary nausea lasting for 1 week in 3; and vaginal dryness in 2 patients. Serum estrogen levels dropped by 20% in 10 patients from baseline but remained within normal range (14–103 pg/mL), there were no changes in serum testosterone (range 14–76 ng/mL) or prolactin (2.8–29 ng/ml) levels. 2 out of 4 patients with joint pains had testosterone levels in upper range, and remained unchanged during treatments. Conclusions: Anastrozole 1 mg daily is well tolerated in clinical practice, in terms of side effects and does not cause significant blood hormonal changes.

No significant financial relationships to disclose.
Treatability of patients with metastatic breast cancer after treatment by ixabepilone in first-line
Authors: Thivat E. , Dalenc F. , Durando X. , Gladieff L. , Mouret-Reynier M. , Kwiatkowski F. , Deslandres M. , Chollet P. , Roché H.
Published: August 2020

e12030

Background: Ixabepilone (BMS-247550), an epothilone B analog, was an active drug in metastatic breast cancer (MBC) patients who were anthracycline pretreated. The main toxicity was mild to moderate neuropathy which was primarily sensory and mostly reversible. This study was performed to evaluate retrospectively the treatability of patients after discontinuation of ixabepilone given as first metastatic line in 2 institutions. Methods: From February 2001 to December 2002, 50 patients (median age 54 years) were enrolled in a phase II clinical trial evaluating ixabepilone as first line chemotherapy (CT) in MBC. Fifteen patients were treated by 50 mg/m2 (as a 1-hour infusion subsequently amended as a 3-hour infusion), and 34 received ixabepilone at 40 mg/m2 IV infusion during 3 hours every 3 weeks in response to the early safety findings. Neurotoxicity occurred in 38 patients (76%) leading to treatment discontinuation in 19 patients (38%). The description of subsequent treatments after ixabepilone was realized to detect eventual cross resistance and subsequent neurotoxicity. Results: Patients received a median number of 3 subsequent CT (range, 0–11) whatever the ixabepilone dosage. The median duration of subsequent CT lines after ixabepilone was of 3.6 months (range, 0–15.6 months). Patients who developed neurotoxicity received a median of 3 subsequents CT (range, 0–9), and those who did not, received a median of 1.5 subsequent lines. Forty-four patients received a second metastatic CT with different regimens stratified according the main cytotoxic agents, which were capecitabine in 54.5% of patients, taxane in 18.2%, and vinorelbine in 15.9%. At third line of metastatic CT (n = 37), taxane based regimen, capecitabine based regimen, and vinorelbine based regimen were administered respectively in 45.9%, 16.2%, and 13.5%. Median survival from first administration of ixabepilone was of 25.3 months (range, 0.2–89.2 months). After ixabepilone treatment, best response rate of subsequent CT was of 18.4%, and neurotoxicity was observed in 42.1%. Conclusions: In spite of neurotoxicity development with ixabepilone used as first metastatic line, the administration of subsequent lines of CT for treated MBC, especially with taxane based regimen, was normally possible.

No significant financial relationships to disclose.
Impact of MGMT methylation status on 1p/19q intact anaplastic gliomas
Authors: Franceschi E. , Tosoni A. , Ermani M. , Spagnolli F. , La Torre L. , Galzio R. J. , Pozzati E. , Talacchi A. , Benevento F. , Brandes A. A.
Published: August 2020

e13003

Background: Chromosomes 1p/19q codeletion has been recognized as a prognostic and predictive factor in patients (pts) with grade 3 gliomas. Non-codeleted (intact) anaplastic oligodendroglioma showed a survival comparable to that usually observed in pts with anaplastic astrocytomas; MGMT methylation status, moreover, has been found to be a prognostic factor in glioblastoma and anaplastic gliomas (AG). Methods: A retrospective analysis was made using a database of 253 AG pts followed prospectively between January 1998 and August 2008. We evaluated only pts who met the following inclusion criteria: age ≥ 18 years; PS 0–2; histological diagnosis of AG with 1p/19q intact, as determined by FISH analysis; treatment with postoperative radiotherapy (RT) and chemotherapy (CT); MGMT status determined using methylation specific PCR. The study aim was to evaluate the role of MGMT methylation status in 1p/19q codeleted AG pts. The log-rank test was used to evaluate the significance of the prognostic variables. Results: 67 pts (m/f: 35/32, median age: 41.3 years, range: 18–70 years) were enrolled. Histology was anaplastic oligodendroglioma in 17 pts, anaplastic oligoastrocytoma in 20 pts, and anaplastic astrocytoma in 30 pts; all these pts were 1p19q intact and received surgery, RT, and CT. MGMT status, assessable in 58 pts (86.6%), was methylated in 33 pts (56.9%), and unmethylated in 25 pts (43.1%). Median progression-free survival (PFS) was 32.3 months (95%CI: 9.9–54.7). No enhancement at time of diagnosis (p = 0.003), gross total resection (p = 0.03), age (p = 0.001), and MGMT methylation (p = 0.05) were significantly correlated with better PFS. Median survival was 65.2 months (95% CI: 45–85.3). Only age (p = 0.001) and KPS (p = 0.02) correlated with a better survival. Conclusions: MGMT methylation status may provide adjunctive prognostic information in pts with 1p/19q intact AG, indicating a prolonged PFS in pts harboring MGMT promoter methylation.

No significant financial relationships to disclose.
Phase 1 study of LY317615 (enzastaurin) and temozolomide in patients with gliomas - EORTC trial 26054
Authors: Rampling R. , Sanson M. , Taal W. , Lai C. , Stoffregen C. , Munoz M. , Gorlia T. , Govaerts A. , Lacombe D. , Van den Bent M.
Published: August 2020

e13005

Background: Enzastaurin (Enz) is a small selective inhibitor of protein kinase C (PKC). Synergy with temozolomide (TMZ) has been demonstrated in vitro. This phase I trial investigated optimal dosing and toxicity when Enz was combined with a standard TMZ regimen. Methods: Patients (pts) with recurrent high-grade glioma or newly diagnosed disease not amenable to radiotherapy (RT) and WHO PS 0–1 were eligible. Pts on EIAEDs were excluded. Two dose levels (DL) of Enz were explored. DL1: Loading dose 500 mg followed by 250 mg daily. DL2: Loading dose 1,125 mg followed by 500 mg daily. TMZ was given at 150 mg/m2 d1-d5 every 28 days in cycle 1, escalating to 200 mg/m2 in subsequent cycles. Dose-limiting toxicity (DLT) was defined by CTCAE 3.0 criteria in the first two cycles as (1) any non haematological toxicity grade 3/4 (2) ANC < 500/mm3 (3) thrombocytopenia grade 3/4 (4) any toxicity reducing drug dose intensity to <80%. Results: 15 pts were included, three at DL1, 12 at DL2. 13 pts had received prior RT, seven prior chemotherapy, and two were newly diagnosed. Median number of cycles was four (range 2–8).Treatment is ongoing in five pts. TMZ dose was escalated in all pts with no DLT. Modest and reversible thrombocytopenia was the most frequent toxicity, occurring in seven pts (3 @ Gd 1, 3 @ Gd2, 1 @ Gd 3) and led to TMZ dose reduction in two pts and treatment delays in four pts (multiple in 2). One pt discontinued after three cycles due to persistent thrombocytopenia. Five pts developed neutropenia not requiring dose modification. Two pts developed hyperbilirubinemia. Six SAE's (3 at each DL) were recorded, and one death (DL2). None was considered treatment related. Two pts showed a partial response, six pts stable disease. Conclusions: Enz can be safely combined with standard TMZ regimen. Results of the just completed phase I part with Enz 250 mg twice daily dosing will also be presented at the meeting.

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Five-year survival data in newly diagnosed glioblastoma treated with radiotherapy along with concurrent and adjuvant temozolomide
Authors: Wadasadawala T. , Jalali R. , Munshi A. , Gupta T. , Kalyani N. , Menon H. , Sarin R. , Goel A.
Published: August 2020

e13009

Background: We report 5-year survival data in patients with newly diagnosed glioblastoma treated with radiotherapy along with concurrent and adjuvant temozolomide (TMZ). Methods: Between March 2001 to April 2008, 81 patients with newly diagnosed histopathologically proven glioblastoma underwent surgery followed by external radiotherapy to a total dose of 60 Gy in 30 fractions over 6 weeks. Concurrent oral TMZ (75 mg/m2) was given daily with RT followed by adjuvant TMZ for 5 days every 28 days for six cycles (150 mg/m2 for the first cycle and 200 mg/m2 for rest of the cycles). Patients were monitored clinicoradiologically as per standard practice. Results: Patients aged between 11–73 years with a median age of 49 years (60 males, 21 females). Forty per cent of patients underwent a gross total resection of tumour, 44% had partial resection, and 16% an open or stereotactic biopsy only. 79% of the patients had a post-operative Karnofsky Performance Score (KPS) of >80. All six adjuvant cycles were completed in 68%. The 2-, 3-, 4-, and 5-year survival was 34%, 24%, 11%, and 11%, respectively (95% CI 14.03–21.96). The median overall and progression-free survival was 18 (2–92 months) and 16 months (2–72 months), respectively. On multivariate analysis, completion of all six cycles of adjuvant TMZ was associated with significantly better survival (p = 0.000). Neurological performance score (NPS) of 2–3 (p = 0.06) and Recursive Partitioning Analysis class V (p = 0.093) showed a trend towards poorer outcome. Treatment was generally well tolerated with only 2.5% of patients developing grade 3 anemia, leucopoenia, and neutropenia. Grade 3 or 4 thrombocytopenia was seen in 5% patients. Conclusions: Concurrent radiotherapy and TMZ followed by adjuvant TMZ results in encouraging survival even at a long follow-up.

No significant financial relationships to disclose.
Angiogenesis and expression of estrogen and progesterone receptors as predictive factors of recurrence in meningiomas: A long-term prospective study
Authors: Saavedra D. , Guevara-Salazar P. , Escobar-Arriaga E. , Martinez-Rumayor A. , Rembao D. , Calderon A. , Sotelo J. , Arrieta O.
Published: August 2020

e13013

Background: Meningioma is a bening tumor, with a high rate of recurrence after surgery (80%); the most important relapse predictive factor is the extent of surgical resection; other potentially predictive factors have been studied with poor results. Angiogenesis has an important role in growth and spread of neoplasic cells; previous studies have shown a high incidence of cyclin E (CE), estrogen, and progesterone receptors (ER, PR) in meningiomas. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), vascular density index (VDI), cell proliferation index (CPI), CE, ER, and PR tissue expression in meningioma recurrence of patients submitted to surgical resection. Methods: From January 1995 to December 2000, we enrolled 42 patients with histopathological diagnosis of meningioma and treated only with surgical resection. Tumor VDI, CPI, CE, ER, and PR tissue expression were evaluated by immunohistochemistry in patients with or without recurrence. CPF, VDI, CPI, and expression of CE, ER, and PR were associated with recurrence. Results: Complete surgical resection was achieved in 32.5% of patients. Minimal follow-up was 6 years. Recurrence of meningioma was found in 17 patients (40%). Mean time of recurrence was 32 + 8 months. Tissue expression was positive for CE, ER, and PR in 90.9%, 27.6%, and in 64% of patients, respectively. VDI was >8 (40X in 10 fields) in 52.6% of patients and CPI was >600 (40X in 10 fields) in 54.2% of patients. Significant recurrence-associated factors were extent of resection (RR = 2.4, 95% CI 1.7–2.9, p = 0.03) and VDI >8 (RR = 1.7, 95% CI 1.003–2.9, p = 0.001). CPI, CE, ER, and PR expressions were not statistically significant (p = 0.83, p = 0.16, p = 0.46, and p = 0.74, respectively). Conclusions: Patients with partially resected meningioma and high VDI have an increased recurrence risk and could benefit of additional therapeutic measures.

No significant financial relationships to disclose.
Pilot study of topotecan and thalidomide in patients with recurrent malignant gliomas
Authors: Khosla P. , Monga V. , Taaca A.
Published: August 2020

e13019

Background: Adults with glioblastoma multiforme (GBM) treated with radiation and chemotherapy have median survival of less than 12 months from diagnosis. Topotecan is a topoisomerase-1 inhibitor with activity in brain tumors and very little nonhematologic toxicity. Continuous infusion has been shown to have decreased hematologic toxicity. Thalidomide has antiangiogenic and immnunomodulatory effects. The combination would offer a multitargeted approach with no overlapping toxicity. Methods: Single-center prospective phase II study of 10 patients (median age 50, range 38–70) with high-grade recurrent glioma treated at Rush University Medical Center between 2002 and 2006 following IRB approval. All patients had failed at least one standard therapy and received a combination of the two drugs: topotecan by continuous infusion for 21 days, every 28 days at 0.4 mg/m2/day through a permanent in-dwelling catheter and thalidomide with starting oral dose of 100 mg/day, escalated by 100 mg/day per week to maximum of 400 mg/day by day 28. Dose reductions were made for grade 3 and 4 hematologic or nonhematologic toxicities. All patients received coumadin 1 mg/day DVT/PE prophylaxis. Assessment of response was done every 8 weeks by MRI and MRS. Results: Median number of cycles of study drugs = 3; median time to progression = 4 months; median survival = 12 months; DVT/PE = 40% of patients with low-dose coumadin prophylaxis. Conclusions: The combination of topotecan and thalidomide is feasible and shows moderate activity. The study is limited by small size and thromboembolic complications likely related to thalidomide in 40% of patients. Low-dose coumadin prophylaxis was not adequate in preventing thrombosis.

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No significant financial relationships to disclose.
Clinical significance of prophylactic intrathecal chemotherapy in the treatment of glioblastoma multiforme
Authors: Iuchi T. , Hatano K. , Sakaida T. , Hirono S.
Published: August 2020

e13022

Backgrounds: We previously have reported that hypo-fractionated high-dose irradiation (HdI; 68Gy/8F) showed excellent local control but no effect on prevention of cerebrospinal fluid dissemination (CSFd), resulted in limited efficacy on patients’ survival in glioblastoma (GBM). The aim of present analysis is to evaluate the clinical significance of prophylactic intrathecal administration of thiotepa (iT) in the treatment of GBM patients. Methods: Histologically confirmed GBMs without CSFd at diagnosis were enrolled. Patients were classified into four groups owing to the post-surgical treatment strategy as follows: Group A patients (n = 65) were treated by conventional radiotherapy (cRT; 60Gy/30F) alone; Group B patients (n = 17) were by cRT concurrent witn iT; Group C patients (n = 28) were by HdI alone; Group D patients (n = 30) were by HdI concurrent with iT. In Group B and D, Ommaya reservoir was placed into the lateral ventricle and 10mg of thiotepa was administrated weekly after surgery for five times. The local progression-free survival (PFS), CSFd-free survival (CFS), and overall survival (OS) were compared in these four groups. Results: Group C and D patients showed significantly longer PFS than Group A and B (p < 0.0001), suggesting the clinical significance of HdI for local control of this tumor. On the other hand, CFS in Group B and D was significantly longer than that in Group A and C (p = 0.049), demonstrating the effect of iT for prevention of CSFd. However, significant improvement of OS on the conventional treatment (Group A, median OS: 12.3 months) was observed only in Group D (median OS: 30.2 months, p = 0.002) and not in Group B or C (24 months, p = 0.135, and 14.9 months, p = 0.481 respectively). Conclusions: These data indicated that both of local control and prevention of CSFd were required for better survival of patients with GBM, and iT concurrent with HdI may be one of the treatments that fill these requirements.

No significant financial relationships to disclose.