bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain metastases in HER2-overexpressing metastatic breast cancer: Comparative analysis of trastuzumab levels in serum and cerebrospinal fluid
Authors: Stemmler J. , Schmitt M. , Willems A. , Bernhard H. , Harbeck N. , Heinemann V. 
Published: March 2020

1525 Purpose: Patients receiving trastuzumab for HER2-overexpressing MBC suffer from an increased risk to develop BM despite responsive visceral disease. The present pilot study was conducted to explore trastuzumab levels in S and CSF of MBC patients afflicted with BM, and to evaluate whether radiotherapy will lead to impairment the blood-brain barrier (BBB) to allow penetration of trastuzumab into CSF. Methods: Patients with BM from HER2-overexpressing MBC (IHC; DAKO Hercep Test) were included. Trastuzumab levels in S and CSF were determined at different time points by a newly developed immunoenzymatic test for functional, reactive trastuzumab. Results: Six out of 8 eligible patients were evaluable. Prior to whole-brain radiotherapy (WBRT), the median trastuzumab serum level was 52,054 ng/ml compared to a median CSF level of 124 ng/ml (ratio 420:1). After completion of WBRT, the median level of trastuzumab was 20,185 ng/ml in serum and 226 ng/ml in CSF (ratio 76:1). In two cases of concomitant meningeal carcinomatosis, the median serum level of trastuzumab after WBRT was 17,431 ng/ml and 356 ng/ml in CSF (ratio 49:1). Conclusion: These data indicate that the BBB prevent trastuzumab to reach adequate concentrations in CSF. These levels are increased under conditions of an impaired BBB, as is known for meningeal carcinomatosis and for patients receiving WBRT. The new test system in this pilot study provides the basis for the evaluation of radiotherapeutic strategies which allow most favorable penetration of trastuzumab into the CNS in patients receiving concomitant trastuzumab for HER2-overexpressing metastatic breast cancer. [Table: see text]
Primary intraocular lymphoma (PIOL): An International Primary CNS Lymphoma Collaborative group report
Authors: Grimm S. , Pulido J. , Jahnke K. , Schiff D. , Hall A. , Shenkier T. , Siegal T. , Nancy D. , Batchelor T. , Abrey L. 
Published: March 2020

1534 Background: PIOL is a hemopoietic tumor that arises in the retina, vitreous or optic nerve head, and carries a high risk of ocular and CNS relapse. The natural history and optimal management are unknown. Methods: A retrospective series of 81 patients with PIOL was assembled from 15 centers in 7 countries. Only patients with isolated ocular lymphoma were included; none had brain, spinal cord, or systemic lymphoma at diagnosis. Results: The median age at diagnosis was 65 (24–85). 58% were women. The median ECOG performance status was 0, and only three had a score > 1. The median latency from symptom onset to diagnosis was 6 months (0– 36). Slit lamp exam was positive in 51, negative in 6, and not reported in 24. Vitrectomy was positive in 72 and negative in 2. 6 had a positive choroidal or retinal biopsy and 1 had no ocular surgery. CSF cytology was positive in 10 (17%), negative in 48, and unknown in 23. 21 received local therapy at diagnosis: 6 intra-ocular methotrexate (400 ug), 14 ocular radiation (median 3600 cGy), and 1 both modalities. 52 received more extensive therapy including systemic chemotherapy alone in 20 and a combination of chemotherapy and radiotherapy in 32. 5 received no treatment and details are unknown in 3. 47 patients (58%) relapsed a median of 19 months (0.5–180) after initial therapy. Sites of relapse included brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Patients treated with ocular therapy alone did not have an increased risk of failing in the brain (p = 0.6). Progression free survival (PFS) and overall survival (OS) were 29.6 and 57 months respectively and were unaffected by the choice of therapy. CNS disease was the cause of death in 19/33 (58%). Conclusions: In this series, treatment type did not affect sites of relapse, PFS or OS in patients with PIOL. To minimize toxicity, the best initial therapy should be limited to intraocular chemotherapy or focal radiotherapy. Prospective clinical trials are needed to improve our understanding and treatment of this disease. No significant financial relationships to disclose.
Phase II study of concurrent temozolomide and whole brain radiation therapy in patients with brain metastasis
Authors: Dawood S. , Ragaz J. , Navaratnam S. , Mihalcioiu C. 
Published: March 2020

1540 Background: 30% of patients (pts) with lung cancer develop brain metastases, with XRT representing the conventional treatment of multiple BM. Methods: Pts with lung cancer, Brain metastases (BM) and performance status of 0–2 were enrolled. TMZ (75mg/m2 day 1–14) given on cycle 1 with XRT (3000cGy in 10 fractions) followed by cycles 2–4 TMZ (200mg/m2 day 1–5, q 4 weeks). Pts with active systemic disease received also chemotherapy (cisplatin or docetaxel or paclitaxel) during TMZ cycles 2–4. Primary end points: 1. Radiological response of BM assessed after 4–6 weeks from the end of XRT, 2. Treatment related toxicity, 3.Functional Scale score(FSS)(1 best, 3 worst, based on interaction of WHO performance status, score 0–4, with the neurological status score 1–3). FSS was assessed at baseline, and during the follow up visits. Secondary end points: time to progression and overall survival. Results: 22 patients enrolled, 8 pts received TMZ alone and 14 pts had additional chemotherapy. CR was documented in 2 pts, PR in 6 pts, SD in 5 pts, 4 pts progressed on treatment; 5 pts were not evaluable (death from other causes within 2 months from diagnoses). FSS at baseline was available on 19/22 patients. Of those, thirteen, four and two pts had a FSS of 1, 2 and 3, respectively. Fifteen of the 19 pts maintained their FSS at the end of Tx, with 3 pts exhibiting deterioration, and one patient improved. Post treatment FSS remained stable in 16 patients up to one month prior to death. The median survival (22 pts) from the time of diagnosis of BM was 9 months with average TTP of 3.5 months. Except for moderate nausea and vomiting there was no significant toxicity by combining TMZ with XRT. The addition of single agent chemotherapy to TMZ was well tolerated but two patients who required GCSF support. Conclusion: Adding TMZ to XRT for the treatment of BM from in lung cancer patients showed a response in 13 out of 17 assessable patients with a median survival of 9 months which is above the mean 3 to 6 months survival reported in the literature with XRT alone. More importantly, the majority of patients maintained a stable FSS up to one month prior to death suggesting a quality of life benefit during most of their life span. TMZ can be safely administered concomitantly with either XRT or with other single agent chemotherapy. No significant financial relationships to disclose.
Radiosurgery alone for solitary and multiple brain metastasis
Authors: Fox J. L. , Kleinberg L. , Kharkar S. , Clatterbuck R. E. , Wang P. , Wharam M. 
Published: March 2020

1541 Background: Whole-brain radiation (WBRT) in the management of brain metastases treated with radiosurgery (RS) is controversial. Methods: Ninety-eight patients were treated for brain metastases with RS at Johns Hopkins between 4/03 and 7/05. Twenty-eight patients received RS alone after failing WBRT, 33 received RS alone for initial metastases and 37 received RS along with WBRT. Forty-five patients were women and 53 were men, with a median age of 56 (range, 18–92). Histology was: non-small cell lung cancer - 35, breast -14, melanoma -10, renal cell carcinoma - 9, and other - 30. Ninety-two (94%) pts had a KPS of ≥ 70 (median 80). The median number of metastases was 2 (range, 1–14). Results: Follow-up data from date of RS was available for 96 patients. Among those who received RS along with planned WBRT, median survival (MS) was 6.6 months with 1-yr overall survival (OS) 38%. Among patients treated initially with RS alone, MS was 9.7 months with 1-yr OS 42%. Among patients treated with RS for recurrent metastases after prior WBRT, MS was 6.8 months with 1-yr OS 24%. There were no significant differences in survival amongst these 3 treatment groups (p=0.73, log-rank test). For patients with 1–3 metastases (n=66), 1-yr OS was 38% versus 32% for those with ≥ 4 (n=32). Median survivals were 8.4 and 6.7 months, respectively (p=NS). Of patients treated with RS for recurrence, 7 of 25 (28%) with available follow-up data developed recurrent or new metastases whereas 11/27 (41%) treated with RS and planned WBRT and 15/27 (56%) who had RS alone as initial treatment had documented recurrent or new metastases. Conclusions: RS alone may be an effective treatment that preserves survival for those with single or multiple brain metastases at initial presentation or recurrence, but the tradeoff between the marginal increase in risk of brain recurrence versus toxicity and time commitment for WBRT needs further evaluation. The ongoing US Intergroup randomized trial, N0572/Z300, will address some of these questions. No significant financial relationships to disclose.
Palliative whole brain radiation therapy (WBRT) for brain metastases (BM) revisited: The patient population in the modern era is different from the original patient cohort of the RTOG WBRT clinical trials
Authors: Savetsky S. RushM. , Vinokur A. , Mehta N. 
Published: March 2020

1544 Background: RTOG trials in the 1970’s established WBRT (3000 cGy/10 fractions) as an effective palliative tool for symptomatic BM. This was in the era before CT/ MRI and effective systemic therapy. Inclusion criteria was based on clinical symptoms, and studies such as EEG and arteriography though not required. This study was undertaken to determine if pts. in the modern era are similar to those aforementioned, since it may not be appropriate to use accelerated WBRT (aWBRT) in these pts. based on the RTOG guidelines if the cohorts are different. (Other issues such as delayed cognitive dysfunction, alopecia and the impact of and integration with systemic therapy are pertinent to the application and prescription of aWBRT, but not the focus of this study). Methods: A retrospective chart review of 414 consecutive pts. with BM treated with radiation therapy in a single practice from 1990 through 2004 form the basis of this study. There were 256 females and 158 males. Lung cancer was the most common primary site (249/60%) and breast cancer next (75/18%). 121 pts (29%) had a single brain metastsis. 66 symptomatic patients underwent surgical resection of a brain metastasis prior to WBRT. The use of CT or MRI was determined. Results: Of the 414 pts, 105 were asymptomatic (25%). An additonal 66 pts. were rendered asymptomatic with surgical resection. Therefore, a total of 171 (40%) pts. were asymptomatic. All pts underwent imaging with CT (132) or MRI (282). Conclusions: Many pts. with BM seen in a modern radiation oncology practice are different from those in the RTOG series’ in which pts. were designated to receive aWBRT. 1. A notable proportion (40%) of a large number of pts. treated since 1990 for BM was asymptomatic vs. none of the pts. in the RTOG trials. 2. All pts. in this series underwent direct imaging vs. none in the RTOG series’. The systematic prescription of aWBRT for all pts. with BM as dictated by RTOG studies in the 1970’s may not be appropriate and alternative strategies and clinical trials are warranted. No significant financial relationships to disclose.
Chemokine receptors seem to impact on patient survival in head and neck squamous cell carcinoma
Authors: Federico M. H. , Campofiorito C. M. , Mangone F. R. , Maistro S. , Pasini F. S. , Brunialti K. C. , Lehn C. N. , Walder F. , Carvalho M. B. , Brentani M. M. , Snitcovsky I. 
Published: March 2020

15527 Background and Methods: Chemokine receptors seem to be involved in tumor spread to lymph nodes and influence outcome in cancer patients (pts). Here, we have determined the mRNA expression of CCR7, CX3CR1 and CXCR1 chemokines, by means of Ribonuclease Protection Assay, in 60 fragments of primary tumor and matched adjacent mucosa of pts with head and neck squamous cells carcinoma (HNSCC) submitted to curative surgery. For Kaplan Meier survival curves, pts were categorized for each chemokine as positive or negative if above or equal/below median densitometric value of the entire tumor group. Results: In the whole study population, CCR7 status did not impact on overall survival (OS) (P=0.118, Log Rank) and on disease free survival (DFS) (P = 0.102), neither. When the subgroup of oral SCC was considered (n = 19), the CCR7 negative pts (n = 10) presented a longer DFS and OS (median DFS and OS not reached) as compared to CCR7 positive pts (n = 9) (mDFS: 4.9 months, P = 0.001 and mOS 10.47 months P = 0.003). In the HNSCC group as a whole, the CX3CR1 negative pts presented a trend toward longer OS (mOS 26.60 months in negative group, n = 25 vs 15.43 months in the positive group, n = 35, P = 0.073) and a longer DFS (mDFS not reached in CX3CR1 negative vs 9.20 months in positive pts, P = 0.041). In the oral SCC subgroup, CX3CR1 negative pts (n = 8) presented significantly better DFS (mDFS not reached) as compared to CX3CR1 positive pts (n = 11, mDFS 4.9 months, P = 0.004). OS was also superior for oral SCC CX3CR1 negative (mOS not reached) as compared to positive pts (mOS 10.47 months, P = 0.008). Taking into account larynx SCC, mDFS and mOS were not reached for CX3CR1 negative pts (n = 5) as compared to positive pts (n = 11, mDFS 8.57 months, P = 0.016; mOS 12.37 months, P = 0.041). In larynx subgroup, the other receptor associated to an advantage in terms of both DFS and OS was the negativity for CXCR1 (mDFS not reached for negative vs 8.47 months for positive pts, P = 0.006; mOS not reached for negative vs 8.47 months for positive pts, P = 0.025). Conclusions: Even if the mechanisms are not clear, our data suggest that low expression of CCR7, CX3CR1 and CXCR1 mRNA may be markers of better outcome in Head and Neck Squamous Cell Carcinoma. Further studies are warranted to confirm these results. No significant financial relationships to disclose.
Results of G004, a phase IIb study in recurrent glioblastoma patients with the TGF-b2 targeted compound AP 12009
Authors: Bogdahn U. , Oliushine V. E. , Parfenov V. E. , Kunst M. , Mahapatra A. , Sastry K. V. , Venkataramana K. N. , Jachimczak P. , Hau P. , Schlingensiepen K. 
Published: March 2020

1553 Background: In high-grade glioma (HGG), TGF-β2 expression strongly correlates with tumor grade and is highly predictive of disease outcome. The compound AP 12009 inhibits TGF-β2 expression. Preclinical results revealed strong multimodal activity including reversal of TGF-β induced immunosuppression, inhibition of tumor cell migration and proliferation. In 3 preceding phase I/II dose escalation studies, 24 HGG patients had been treated with AP 12009. Methods: G004 is an international open-label, actively controlled, dose finding phase IIb study. Objective is a comparison of two doses of AP 12009 and standard chemotherapy for efficacy and safety. 145 patients with histopathologically confirmed recurrent anaplastic astrocytoma (AA, WHO grade III) or glioblastoma (GBM, WHO grade IV) were randomized into one of 3 treatment arms. 134 patients received treatment AP 12009 10μM, AP 12009 80μM or standard chemotherapy (TMZ or PCV). AP 12009 was applied locoregionally by convection-enhanced delivery during a 6-month active treatment period with 7-day-on, 7-day-off cycles. Primary endpoint is tumor response by local and central MRI reading. All patients have completed active treatment. Follow-up for survival and tumor response assessed by local and central MRI reading is ongoing. Results: Here we report on patients with recurrent GBM (AA see separate Abstract). 96 GBM patients (37% female, 63% male; median age 51 years, range 20–74; median Karnofsky performance status 90, range 70–100) have been treated. 63 GBM patients received AP 12009 (28 pt. 10 μM, 35 pt. 80 μM), 33 patients received standard chemotherapy. Data were evaluated by an independent Data and Safety Monitoring Board. Up to now, in 89 patients treated with AP 12009 (AA and GBM patients) 6 SAEs possibly related to the study drug and 37 procedure related SAEs (92% mild or moderate) were documented. Several long-term tumor responses were observed by local MRI reading. Exact response rates are being determined by central reading. Conclusions: Responses in patients treated with AP 12009 in both AA and GBM patients are long lasting with a good quality of life. Phase III clinical trials in AA and GBM patients are currently in preparation. [Table: see text]
Multimodal therapeutic approach in anaplastic thyroid cancer
Authors: Lee Y. , Jung J. , Hwang G. , Park H. , Im Y. 
Published: March 2020

15533 Background: Anaplastic thyroid cancer (ATC) is a rare but highly aggressive neoplasm with a dismal prognosis. However, a few patients survive for a long time after treatment. We tried to identify prognostic factors of this disease and analyzed treatment outcomes in patients with ATC. Methods: We reviewed the medical records of 15 patients diagnosed with ATC in our institution between 1988 and 2003. The survival was compared by the Kaplan-Meier log-rank test. Results: The female-to-male ratio was 1.5:1 (9 women and 6 men), and the mean age at diagnosis was 63.9 years (range, 44–91). The mean tumor size was 6.3cm (range, 4–10 cm). Extrathyroidal invasion was present in 12 cases and distant metastasis at diagnosis was present in 6 cases. Surgery was performed in 8 cases. Radiotherapy was used for 10 cases and chemotherapy for 5 cases. The mean overall survival time of the 15 patients was 237 days (range, 28–717 days). The 6-, 12-, 18- and 24-month survival rates were 33%, 26%, 13% and 0%. No association was found between survival and presenting symptoms, age, gender, tumor size, previous goiter history, extrathyroidal invasion, distant metastasis, surgery, radiotherapy or chemotherapy. A significantly better outcome was observed in patients received triple modality treatment (surgery, radiotherapy and chemotherapy) than in those received single or dual modality treatment (P = 0.05). Conclusions: Although most patients with ATC had a poor prognosis, a multimodal approach including surgery, radiotherapy and chemotherapy, might improve survival. No significant financial relationships to disclose.
Follow-up of concomitant treatment with gemcitabine/radiotherapy in locally advanced squamous cell carcinoma of head and neck
Authors: Bustamante F. , Villalobos R. , Castillo E. , Calva A. , Gallegos F. , Silva A. , Castruita A. 
Published: March 2020

15537 Background: The stages of the locally advanced head and neck cancer have a negative prognosis, therefore, new treatments are continuously explored. One of these treatments consists of the use of Gemcitabine concomitant with radiotherapy. We previously evaluated the rate of response and the toxicity profile of this treatment in 15 patients and now we are reporting the follow up of such study. Methods: Fifteen patients, with histological report of locally advanced squamous cell carcinoma of head and neck, initiated treatment of Gemcitabine at intravenously doses of 50 mg\m2 per application weekly concomitant with radiotherapy. The radiotherapy consisted of an initial photons dose of 3960 cGy in 22 fractions of 180 cGy to the primary site and regional lymph with posterior increments of 2880 cGy in 16 fractions of 180 cGy excluding the spinal cord and electrons increments if necessary. Results: In 9 of the 15 patients complete response was obtained, achieving organ preservation. Four of the 15 patients presented a partial response and two presented progression. The principal severe toxicity presented was mucositis. The mean follow-up is 23 months with a range of 19–27 months. From the 9 patients that presented a complete response, one presented bone recurrence 13 months after achieving the total response; another one of them died because an infectious process without evidence of tumoral activity. The rest 7 patients are to the present date without evidence of tumoral activity. One of the patients with partial response is still alive with tumoral activity in central nervous system. The remaining patients died due to tumoral activity. Conclusions: In our study with 15 patients an overall response of 87% was obtained. With a follow up to 23 months only one recurrence has been presented. We concluded that the treatment is feasible and it could have an impact in the overall survival but studies with a greater number of patients and a larger follow up are needed. No significant financial relationships to disclose.
Evaluation of combined modality treatment for advanced nasopharyngeal carcinoma by induction chemotherapy and radiotherapy
Authors: Tran T. Q. , Vu V. V. , Vo D. K. , Pham K. C. 
Published: March 2020

15544 Background: We performed a retrospective investigation of the combined induction chemotherapy and radiotherapy for advanced nasopharyngeal carcinomas at Cancer Center-Ho Chi Minh City-Vietnam. Method: In the period 1998–2000, the treatment regimen induced 2 or 3 cycles of cisplatin and 5-Fluorouracile followed by radiation. Cisplatin was given in the dose of 100 mg/m2/day 1 and 5FU 1,000 mg/m2/d1–4. Radiotherapy included 2 lateral cervical portals and an anterior cervical portal with Cobalt 60. Results: One hundred sixteen patients (92 men and 24 women) with age ranging from 15 to 72 years were enrolled. The overall response rate to induction chemotherapy was 66% (15% complete responses (CRs) and 51% partial responses (PRs)). After combined treatment, overall response rates was 92% (82% CRs, 10% PRs). Toxicities in the chemotherapy were mainly myelosuppression (40%), nausea/vomiting (27%), mucositis (28%), and diarrhea (12%). There was 9 recurrences (2 local, 7 distant), 7 deaths and 1 refusal of radiotherapy. Conclusion: The immediate local response rates was rather high despite of the common of major myelotoxicities and expensive cost. The long-term survival benefit need to be reevaluated carefully later. No significant financial relationships to disclose.