bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra-arterial chemotherapy with docetaxel and cysplatin in combined treatment of patients with locally advanced squamouse cell head and neck cancer (SCHNC)
Authors: Adilbayev G. , Adilbay D. , Kim G. , Ahmetov D.
Published: March 2020

15528

Background: Currently the main role in chemotherapy of head and neck cancer from the 90ths is related to taxans. To elevate the effect of combination docetaxel + cysplatin and to reduce their toxic influence to the organism we have studied intra-arterial path of delivery at the combined therapy of head and neck cancer. Methods: We treated 53 patients with locally advanced SCHNC(T3, T4). All patients received 2 courses of intra-arterial chemotherapy by catheterization the feeding arteries of tumor through the external carotid artery: docetaxel-80 mg/m2, cysplatin-100 mg/m2. Further, depending on the results of chemotherapy, there were performed radiotherapy and surgical treatment in necessary volumes. Results: By analyzing the effect of docetaxel + cysplatin combination in different tumor localizations, we have concluded that the best results have been achieved in oral cavity cancer: 9 (29.1%) patients with CR and 16 (51.6%) patients with PR. Worst results have been achieved in maxilla cancer: 0 CR and 14 PR (63.6%). Hematologic toxicity of chemotherapy has manifested only in 18.8% patients (I, II grade). Non-hemathologic toxicity: alopecia 67.9%; periphery neuropathy 11.3; mucositis 5.3%. Performing radiotherapy as the second stage after chemotherapy has increased the number of patients with CR, in patients with oral cancer up to 45.1% and with maxilla cancer up to 18.1%. All results has been confirmed by cytomorphology. As of now surgical treatment has been performed for 30 patients (56.6%). 86.8% patients have been followed up for 6 to 30 months. Conclusion: This neoadjuvant intra-arterial chemotherapy with docetaxel + cysplatin allows both increasing the results of combined therapy and reducing the toxicity of chemotherapy.

No significant financial relationships to disclose.
Pilot study of paclitaxel and carboplatin (P/C) with concurrent radiation therapy (RT) in high risk salivary gland carcinomas (SGC)
Authors: Langston M. , Farray D. , Ruzich J. C. , Emami B. , Petruzzelli G. , Clark J. I.
Published: March 2020

15538

Background: Standard therapy for high risk SGC includes surgical resection with adjuvant RT, but a high risk of recurrence exists. The role of chemotherapy in this setting has not been fully defined. Methods: This limited institution pilot study evaluated the use of P/C with concurrent RT as adjuvant treatment of high risk SGC. The primary objective was to assess toxicity of this treatment in anticipation of a larger cooperative group phase II study. Eligible patients (pts.) had a Southwest Oncology Group (SWOG) performance status (PS) of 0–2 who after surgical resection of their SGC had high risk features including positive surgical margins, perineural invasion, multiple lymph node (LN) metastases, or extracapsular extension. Treatment included P = 40 mg/m2 intravenously followed by C = AUC of 2 concurrently on days 1, 8, 15, 22, 29, 36 of RT. RT consisted of a total dose of 60 Gy in 30 fractions to the primary and regional LN sites of disease. Results: Five pts. were enrolled 4 with adenoid cystic CA and 1 with high grade mucoepidermoid CA. Median age was 59 years (32–69), all with SWOG PS = 0. Four pts. completed the full 6 cycle P/C chemotherapy; all completed RT per protocol. Grade III/IV mucositis, the most common toxicity, occurred in 6 of 30 (20%) P/C cycles, leading to alteration of therapy in 1 pt. There was no reported neuropathy or significant laboratory abnormalities. Median follow up was 17.5 months (mos.); most were disease free at last follow up (13 to 37 mos.); 1 recurred at 14 mos.; this pt. accounts for the only death observed. One year survival was 100%. Conclusions: The regimen of P/C with concurrent RT, as defined, was tolerated well. Grade III/IV mucositis was the main toxicity. Based on the overall tolerability of this regimen, we believe that this postoperative combined modality therapy deserves further study in a larger cooperative group phase II trial to further define its toxicity and efficacy in high risk SGC. We thank Bristol Myers Squibb for support of this study.

No significant financial relationships to disclose.
Phase II trial of imatinib mesylate and hydroxyurea for grade III malignant gliomas
Authors: Desjardins A. , Reardon D. A. , Quinn J. A. , Rich J. N. , Vredenburgh J. J. , Sathornsumetee S. , Salvado A. , Friedman H. S.
Published: March 2020

1573

Background: We evaluated the combination of imatinib mesylate (Gleevec) and hydroxyurea in WHO grade III malignant gliomas following the encouraging response of this combination demonstrated in glioblastoma multiforme. Methods: Eligibility: adult patients with recurrent/relapsing AA or AO with measurable disease; 2 weeks since surgical resection or 4 weeks since radiotherapy or chemotherapy; Karnofsky 60% and adequate organ function. Imatinib and hydroxyurea were given orally daily. Imatinib was administered at 400 mg daily to patients not on enzyme inducing antiepileptic drugs (EIAED) while those on EIAED received 500 mg twice a day. Hydroxyurea was administered to all patients at 500 mg twice a day. Each cycle was 28 days of therapy. Results: Thirty-nine patients with recurrent AA (n= 32) or AO (n=7), following prior radiation therapy and chemotherapy, have been enrolled, including 21 (54%) not on EIAED and 18 (46%) on EIAED. Patient characteristics were comparable between both strata. Median age was 39 years (range, 21–59 years). The most frequent grade III-IV toxicities were neutropenia (n=11), leukopenia (n=8), thrombocytopenia (n=6), deep venous thrombosis (n=3), fatigue (n=2) and pulmonary edema (n=2). One patient presented grade V brain hemorrhage at the time of disease progression. Four patients achieved a partial response, for an overall response rate of 10%. Thirteen patients (33%) achieved disease stabilization. Twelve patients (67%) not on EIAED had progressive disease as their best response compared to only 4 patients (27%) on EIAED. The median time to progression for all patients, and for those not on EAIED and on EIAED was 14.1 weeks, 10.9 weeks and 26.0 weeks, respectively. Conclusions: Daily imitanib mesylate plus hydroxyurea demonstrates encouraging activity and is well tolerated among patients with recurrent AA or AO. As observed with glioblastoma multiforme patients, patients on EAIED seem to demonstrate a better response.

[Table: see text]
Survival improvement by systemic chemotherapy in adult patients with recurrent glioblastoma multiforme treated with two courses of radiotherapy
Authors: Nieder C. , Grosu A. L. , Astner S. , Andratschke N. , Molls M.
Published: March 2020

1578

Background: We evaluated the added value of systemic chemotherapy (CTx) in adult patients with recurrent supratentorial glioblastoma multiforme (GBM) selected to receive local re-treatment (administered as a 2nd course of radiotherapy, RTx). Methods: Retrospective comparison of two patient cohorts treated subsequently during different time periods. All patients had histologically confirmed recurrent GBM. Minimum recurrence-free interval was 4 months. The first cohort (n=26) had surgical resection and standard postoperative external beam RTx followed by a second course of external beam RTx for recurrence (median cumulative dose 102 Gy). None of these patients ever received CTx during the whole course of disease. The more recently treated cohort (after 1999) of 19 patients also had surgical resection and 2 courses of external beam RTx (median cumulative dose 90 Gy). After primary local treatment, 9 of these patients had adjuvant nitrosourea-based CTx. At recurrence, all 19 patients received temozolomide 150–200 mg/m2/day for five days every 4 weeks in addition to RTx. Results: The cohort without CTx had less favorable baseline characteristics, because of their significantly lower median KPS at recurrence (70 vs. 90%, p<0.01) and shorter interval between primary diagnosis and recurrence (12 vs. 16 months, p<0.05). However, these patients were non-significantly younger (median age 44 vs. 50 years, p>0.05). The percentage of patients with secondary GBM was similar (21 vs. 23%, p>0.5). Median survival from re-irradiation was significantly better in the RTx plus CTx group, 9 vs. 5 months (p<0.05). In multivariate analysis, prognosis was significantly improved by CTx. Importantly, there was also an advantage when overall survival from first diagnosis was evaluated, median 24 vs. 19 months (p<0.05). Conclusion: The current data suggest that re-irradiation plus temozolomide is better than re-irradiation alone. CTx led to a prolongation of overall survival from first diagnosis by 5 months. The most intensively treated, prognostically favourable de-novo GBM patients had surgical resection, 2 courses of RTx and 2 different systemic CTx regimens.

[Table: see text]
The cost of treating pancreatic cancer: A pilot study
Authors: Ogdie A. R. , Lee B. C. , Li J. , Maglaris D. , Siddiqi A. , Marshall J.
Published: March 2020

16004

Background: The treatment of pancreatic cancer (PC) is rapidly changing with the approval of new anti-cancer agents. A pilot analysis of twenty five patients treated for PC was performed to determine the cost of PC treatment. Methods: Twenty-five PC patients were selected from 1998–2004 to represent a variety of treatments, both standard and experimental. Charts were reviewed for hospitalizations, clinic visits, and medications greater than $10 in cost. Costs were determined using pharmacy and hospital billing services. Average costs per month were calculated for all 25 patients in the twelve months preceding death. Results: Mean time from diagnosis to death was 13.6 months and mean duration of treatment was 12.6 months. During the period of treatment, mean monthly anti-cancer treatment and additional pharmacotherapy costs were $3,771 and $3,196 respectively. Mean monthly cost of hospitalizations and clinic visits were $2,258 and $213. In the last twelve months of life, months -3, -5, and -2 (death = 0) were most expensive with average spending of $65,557, $58,820, $47,727 respectively. Breakdown of costs in the three most expensive months was: anti-cancer agents (82%), hospitalization (15%), additional pharmacotherapy (3.0%), and clinic visits (0.5%). Conclusions: In this pilot study, we compiled major contributors to the cost of treating PC and then focused on the twelve months preceding death. Anti-cancer agents were determined to be the largest expenditure overall, and were a greater proportion of the cost in the most expensive months before death. This remains an underestimate as surgery, radiation, and indirect costs are not included. As newer agents become incorporated into standard treatment for PC, costs are expected to rise further. This data is being used in designing a larger study comparing costs, quality of life, and survival using newer combination chemotherapy.

No significant financial relationships to disclose.
The development of an outpatient chemotherapy medication safety program
Authors: Hoverman J. R. , Richardson D. , Hansen K. , Dugger P. C. , Shuey K. M.
Published: March 2020

16005

Background: Through Institute of Medicine publications (To Err is Human) and through the public experience of a major cancer center, chemotherapy safety has been of concern. US Oncology, Inc. (USON) is the nations largest oncology management company, associated with over 900 medical, radiation, gynecologic and pediatric oncologists. In 2004 USON undertook a quality initiative with a principal objective a system-wide approach to medication safety. Methods: Medication safety was identified as a principal concern by a combined clinical/management committee. A questionnaire was prepared for each practice site to differentiate high performing practices in regards to variances from lower performing practices. 8 high performing practices and 8 lower performing practices were physically evaluated by team members. Neither the questionnaire nor onsite evaluation reliably differentiated quality processes. Three issues became apparent: no uniform reporting mechanism, multiple “double-check” interpretations and variable inclusion of medication safety into practice operations. The safety team undertook these first two issues. An online reporting tool was developed. “Double-check” was defined and processes mapped. Results: The team chose 1st hour of chemotherapy as the denominator for medication occurrence reporting. An online reporting tool was developed with now 1 year of experience. 83% of practice sites are reporting, accounting for 445,148 1st hours of chemotherapy. The occurrence rate is 0.66%. Of the total 0.13% is adverse drug reaction, 0.10% is near miss, 0.08% is miscalculation of dose, 0.05% is the wrong dose. Injury to a patient is a very rare event. Conclusions: The development of a culture of quality in an organization with affiliations of national scope is a formidable undertaking. These initial numbers have no comparative measure, as this is self-reporting using a novel denominator. However, there are within the network similar groups for comparison. The challenge continues to be developing a culture of reporting with systematic integration of those reports and quality processes into the fabric of the practice.

[Table: see text]
Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (D.O.S.E.) Registry: Analysis of outcomes and costs of epoetin alfa (EPO) and darbepoetin alfa (DARB) treatment in cancer patients
Authors: Memisoglu A. , Peake C. , Buscaino E. , McKenzie R. S. , Forlenza J. B. , Piech C. T.
Published: March 2020

16009

Background: NCCN anemia treatment guidelines recommend hemoglobin (Hb) levels be maintained between 11 and12 g/dL. To understand erythropoiesis-stimulating therapy (EST) dosing, outcomes and costs in cancer patients, data were analyzed from an ongoing prospective, observational registry (D.O.S.E. Registry) collecting real-world data on cancer patients treated for anemia in U.S. oncology clinics. Methods: Data were collected from participating hospital- and community-based outpatient oncology practices between 1/2004 and 11/2005. This analysis included adult patients who had received ≥2 doses of either EPO or DARB. Outcomes assessed included Hb values at weeks 4, 8, 12, and 16 following EST initiation. Drug cost was based on EST utilization and 2005 wholesale acquisition cost. Results: 652 patients (235 EPO, 417 DARB) from 32 sites were identified. Baseline characteristics of age, gender, Hb, tumor type and ferritin level were similar between treatment groups. The proportion of patients with iron supplementation at baseline was significantly higher in the DARB-treated group (EPO 18% v. DARB 31%, p < 0.001). EPO-treated patients were maintained between 11 and 12 g/dL throughout the therapeutic duration ( Table ). Mean cumulative administered dose of EPO was 393,047 Units and DARB 1205 mcg, corresponding to an overall drug cost of $4,783 for EPO and $5253 for DARB (p = 0.001). Conclusions: These results demonstrate that EPO-treated patients maintained target Hb levels consistent with NCCN guidelines, which was not observed in the DARB-treated patients. Drug cost was significantly higher in the DARB group compared to the EPO group without considering the costs of iron supplementation.

[Table: see text]

[Table: see text]
Demographics and disease processes of patients seeking second medical hematology/oncology opinions at a tertiary care center in the United States
Authors: Curtis K. K. , Northfelt D. W.
Published: March 2020

16018

Background: Second opinions (SO) are common in medical practice. Aside from case series, little evidence exists to demonstrate a clinical benefit associated with SO. Lack of relevant data limits knowledge of numbers of patients, diseases, and motivations of SO seekers. Within the field of medical hematology/oncology (H/O), no specific demographic data are available to characterize patients seeking SO in the United States. Methods: To typify such patients at Mayo Clinic in Arizona (MCA), we recorded demographic and disease-related information for patients seeking these evaluations over a six month period from 1/1 through 6/30/05. Results: A total of 683 patients contacted MCA for medical H/O SO over the 6 month study period. A complete set of demographic and disease-related information was obtained from 655 patients; the remainder were excluded from the data set. Demographically, the majority of patients were female (53%), married (66%), and lived nearby (i.e., from Arizona-58%, or bordering state-22%). Average age was 62.3 years. Among oncologic diagnoses, the majority of patients (60% of 374 reported oncologic diagnoses) stated a diagnosis of breast, lung, colorectal, pancreatic or prostate cancer. Approximately 1/3 of patients had metastatic disease at the time they sought evaluation at MCA. There were 278 patients seeking evaluation for hematologic abnormalities, with the majority (160 patients, 58%) seeking evaluation for non-malignant conditions. Of those with malignancies, lymphoma (including Hodgkin and non-Hodgkin) was the most common (45%), followed by multiple myeloma (21%) and chronic lymphocytic leukemia (15%). Conclusions: This study provides insight into demographics and disease processes of patients seeking medical H/O SO at a tertiary care center in the United States. Although no definite conclusions can be drawn about motivations for seeking H/O SO, future research should examine patient motivation to better understand factors leading to this behavior. Given a lack of evidence for clinical benefit associated with SO seeking, and its potential costliness, better knowledge of demographic and motivational factors may allow for a more constructive approach to be taken toward the needs of SO seekers.

No significant financial relationships to disclose.
Health state utility and toxicities in metastatic lung and breast cancer: A qualitative study
Authors: Bhalla S. , Nafees B. , Stafford M. , Watkins J.
Published: March 2020

16021

Background: In metastatic lung cancer, it is expected that quality of life is impacted both by the efficacy and toxicity. Previous research has reported health states either based on response to therapy or on toxicity, but not in combination. Using methodology applied in breast cancer (Narewska 2005), we developed health state descriptions for advanced non-small cell lung cancer (NSCLC) for use in cost-utility analyses. Methods: An interview discussion and content validation guide was produced based on literature review and clinical input. Response to therapy was described as responding disease, stable disease, or progressive disease. The most common toxicities were selected based on randomized clinical trials. Descriptions of health states were reviewed by clinical specialists. Final health states will be piloted and then used in a societal-based valuation study using standard gamble technique. The contributory effect of disease state and toxicity will be estimated using a mixed model analysis and compared with the data from the previous breast cancer utility study. Results: Eight toxicities were identified: alopecia and grade 3/4 neutropenia, febrile neutropenia, hand-foot syndrome, gastrointestinal (diarrhea/vomiting), rash, stomatitis and fatigue. These were combined with response to therapy to yield 19 health states: 9 responding disease (one with each toxicity plus one with no toxicity), 9 stable disease (one with each toxicity plus one with no toxicity) and one progressive disease (toxicity not included). These health states were reviewed by 6 pulmonary oncologists and 3 specialist nurses. Conclusion: Development of health states that combine both efficacy and toxicity will be useful in evaluating the relative value of therapies for advanced NSCLC and comparison with other diseases. Input by clinical experts has provided validation for the proposed health states. Evaluation of these health states by members of society will provide appropriate perspective for economic evaluations.

[Table: see text]
A report on treatment with rasburicase in 18 adult patients
Authors: Severson D. M. , Wills S. M. , Nguyen M. , Margolis J. H.
Published: March 2020

16024

Background: Tumor lysis syndrome (TLS) is a life threatening complication occurring in highly proliferative malignancies. Chemotherapy often causes rapid tumor breakdown resulting in metabolic derangement, abnormal electrolytes and hyperuricemia. Untreated TLS can lead to renal failure and death. Rasburicase (recombinant urate oxidase) is a novel agent that reduces serum uric acid (SUA) levels in pediatric patients. Here we report on 18 adult patients treated with Rasburicase with highly proliferative malignancies. Methods: We retrospectively identified all adult TLS patients treated with Rasburicase at William Beaumont Hospital, Royal Oak, Michigan. We evaluated pre and post treatment SUA, electrolytes and renal function to determine the effect of a single dose of Rasburicase. Results: Twelve men and 6 women (mean age 56.5 years) received Rasburicase between July 2004 and November 2005. Thirteen patients had a diagnosis of TLS prior to treatment, 5 were treated prophylactically and did not develop TLS, 1 patient died of sepsis within 48 h of treatment and 1 patient died from cerebral hemorrhage within 72 h of treatment. Of the 12 assessable patients with TLS, the mean pretreatment SUA was 11.2 mg/dL and the mean 48 h post treatment SUA was 0.68 mg/dL. All SUA levels returned to normal (2.5–8 mg/dL) within 48 h. Ten patients had elevated pretreatment serum creatinine (Scr) levels (mean 2.5 mg/dL) and 2 patients had normal (0.7–1.5 mg/dL) levels. Within 72 h of treatment 7 of the 10 assessable patients showed improvement (mean reduction 0.6 mg/dL) in Scr. Conclusions: It is notable that while almost all patients had hematologic malignancies, 1 patient was diagnosed with an ovarian malignancy and showed great improvement in both SUA and Scr. Rasburicase reduced SUA levels in this patient group. Further studies on larger adult populations in or at high risk for TLS are necessary to determine statistical significance.

No significant financial relationships to disclose.
A prospective study evaluating the relationship between fatigue and patient satisfaction in advanced cancer
Authors: Levin R. D. , Daehler M. , Lis C. G. , Gupta D. , Wodek T. , Grutsch J. F. , Granick J. , Williams S. , Citrin D. L. , Neelam R.
Published: March 2020

16025

Background: Fatigue is the most common and disabling symptoms experienced by cancer patients. No study has prospectively quantified the relationship between fatigue and patient satisfaction (PS) in advanced cancer. We therefore assessed this relationship before the start of chemotherapy and at 3 and 6 months after treatment at our integrative cancer treatment center. Methods: 294 cancer patients treated at Cancer Treatment Centers of America between 04/01 and 11/04. Of 954 patients at baseline, only 294 were available for follow-up at 6 months. Fatigue was measured using the EORTC QLQ-C30 3-item fatigue subscale. Scores ranged from 0–100, higher scores indicating more fatigue. PS was measured using Ferrans & Powers Quality of Life Index (QLI). Scores ranged from 0–30, higher scores indicating better QoL. The mean fatigue scores were compared using ANOVA across the 3 time periods at baseline, 3 and 6 months. The relationship between fatigue and QLI was evaluated using multiple linear regression at all 3 time points. Results: Of 294 patients, 106 were males and 188 females. 91 had breast ca, 52 colorectal, 43 lung, 25 pancreas, 13 prostate, and 70 had other cancers. 112 were newly diagnosed and 182 had received prior treatment elsewhere. The mean fatigue scores at baseline, 3 and 6 months were 43.6, 37.3, and 41.8 respectively; the scores at baseline and 3 months were significantly different (p = .009). At baseline, after controlling for age, gender, prior treatment history, and tumor stage at diagnosis, every 10 unit increase in fatigue was significantly associated with 1.3 units decrease in QLI health subscale. Similarly at 3 and 6 months after treatment, every 10 unit increase in fatigue was significantly associated with 1.2 and 1.4 units decrease in QLI health subscale. Conclusions: In our study, we found that fatigue is a strong correlate of PS independent of the effects of age, gender, prior treatment history and tumor stage at diagnosis during the first 6 months of treatment. Interestingly, fatigue showed a significant improvement after 3 months of treatment and returned back to baseline levels at 6 months. This finding needs to be investigated further to evaluate the impact of integrative cancer care services on PS.

No significant financial relationships to disclose.
Multiple primary cancer in adults (MPCA)
Authors: Ares S. L. , Polo S. , Ezcurdia L. , Tognelli F. , Mussini S. , Gercovich N. , Rivarola E. , Morgenfeld E. , Gil Deza E. , Gercovich F. G.
Published: March 2020

16027

Background: As a result of the improvement in oncological treatments, MPCA could arise as a more frequent problem in Public Health. The purpose of this retrospective review was to estimate both the incidence and medical features of MPCA pts treated at the Instituto Oncológico Henry Moore (IOHM). Methods: We analyzed 17,100 medical charts from our database since 1987 and identified 378 MPC (2,21%). Then we retrieved data over the last eight years (1997–2005). Those pts with at least two second primary tumors were included in this analysis. They were categorized as synchronous (second tumor diagnosis within the first six months from the first one) and metachronous (all the remaining). Pts with skin cancer different from melanoma were excluded. Results: One hundred and seventy eight (M:73; F:105) out of 8,500 cancer pts (2.09%) had at least two primary cancers. Median age was 59, 64 and 68 yo at the moment of the first, second and third diagnosis, respectively. In 138 (78%) pts, the diagnosis of the second cancer was suspected by clinical findings, while in 40 (22%) pts, it was discovered because of medical screening in an otherwise asymptomatic pt. (See Table below) The most frequent site combination was breast-breast (n = 21). A total of 57 pts (32%) had a family history of oncologic diseases. With a median follow-up of 31 mo (range: 0,57–311) after the second cancer diagnosis, 127 pts are still alive (71,35%) and 51 (28,65%) are dead. Conclusions: In the last eight years, 178 (2.09%) pts had developed MPC, being breast, prostate, colon and lung the most frequent (first and later) localizations, and breast-breast the most frequent site combination. The so-called “screening effect” seems to have a low impact on the studied population.

[Table: see text]

No significant financial relationships to disclose.
The European Organisation for Research and Treatment of Cancer (EORTC) translation procedure for standardized quality of life questionnaires
Authors: Koller M. , Aaronson N. K. , Blazeby J. , Bottomley A. , Johnson C. , Ramage J. , West K.
Published: March 2020

16033

Background: The EORTC Quality of Life (QoL) Group has developed a modular approach to QoL measurement for use in clinical trials in cancer. Questionnaires are used in international trials and standardized translation procedures are therefore required. This report summarizes the EORTC translation procedure, its accomplishments and translation problems. Methods: Translations follow a forward-backward procedure, independently carried out by two native-speakers of the target language. Discrepancies are arbitrated by a third consultant, and solutions are reached by consensus. Translated questionnaires undergo pilot-testing. Suggestions (by patients and users) are incorporated into the final questionnaire version. Most translations are performed by professional translators. The translation procedure is managed and supervised by the Translation Committee within the EORTC QoL Group. Results: To date, the core EORTC QoL questionnaire, the QLQ-C30, has been translated and validated into 62 languages, with a further 12 translations in progress. Translations include all major Western languages, East European languages, Asian languages and also remote languages, such as Xhoza (Africa).The validated, condition-specific questionnaire modules have been translated in up to 37 languages. The following major translation problems were encountered: lack of expressions for specific symptoms in various languages, the quest for formal versus informal versions, recent spelling reforms in several European countries, and different weights of social issues between Western and Eastern cultures. The EORTC measurement system is now registered for use in over 9000 clinical studies in 80 countries worldwide. Conclusions: The EORTC provides a strong infrastructure and methodology to produce high quality translations of their QoL questionnaires for use in international clinical trials. Translation problems have been identified and it will be an important topic for future research to specify whether these problems arise out of procedural/methodological shortcomings or are due to subtle cross-cultural differences in concepts of health, illness and QoL.

No significant financial relationships to disclose.
Use of palonosetron 0.25 mg IV daily and incidence of nausea and vomiting in patients undergoing bone marrow transplantation (BMT)
Authors: Adel N. G. , Khan A. , Lucarelli C.
Published: March 2020

16510

Background: Preparative regimens for BMT are associated with a high incidence of nausea and vomiting, which can negatively affect quality of life. It is important to evaluate the incidence of nausea and vomiting and understand which antiemetic regimens are most effective in these patients in order to improve outcomes. Methods: A retrospective review of patients admitted to the adult BMT Unit at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1/1/05 and 12/31/05 was performed. Currently at MSKCC, palonosetron (0.25 mg IV daily) is used as the main antiemetic agent during the preparative regimen; dexamethasone 20 mg IV is occasionally combined with palonosetron when there is no other contraindication to its use with some preparative regimens. The electronic medical records, as well as the pharmacy computer system, were used to collect demographics, primary diagnosis, BMT type, preparative BMT regimen, days of regimen, whether radiation was included, antiemetic used, and incidence of nausea and vomiting, which were assessed 3 times daily during the administration of the preparative regimen. Results: 176 pts (75 women, 101 men) received BMT; mean age was 50 yrs (18–73). All patients received a highly emetogenic preparative regimen for which the mean duration was 5 days (1–9 days). Over a 1–12 day period the incidence of nausea and vomiting were 78% and 39% in those undergoing an allogeneic transplant compared with 51% and 18% in those undergoing an autologous transplant. Patients with leukemia had the highest incidence of nausea (85%) and vomiting (45%). The rates of nausea and vomiting in those receiving radiation were 81% and 33%, while in those not receiving radiation, the rates of nausea and vomiting were 51% and 20%, respectively. Of patients receiving palonosetron alone, 87% experienced nausea and 41% had vomiting, compared to 48% and 15% for those receiving both palonosetron and dexamethasone. Conclusions: Radiation therapy and allogeneic transplant had higher incidences of nausea and vomiting when compared to autologous transplant. Nausea and vomiting were better controlled in patients receiving palonosetron and dexamethasone compared with those receiving palonosetron alone.

No significant financial relationships to disclose.
Acute heart failure in bone marrow transplantation: Impact of intravenous immune globulin as adjuvant therapy
Authors: Salcedo P. , Shpall E. , Yusuf W. , Roberson S. , Woods M. , Lenihan D. , Durand J.
Published: March 2020

16512

Background: Little is known regarding management or treatment of cardiac failure after bone marrow transplantation. We investigated the management, treatment and outcome of new onset acute decompensated heart failure (ADHF) after bone marrow transplantation (BMT) with beta blockers, ace-inhibitors and adjuvant intravenous immune globulin (IVIG) therapy. Methods: We retrospectively examined 25 patients with ADHF. Eleven of these patients developed congestive heart failure within 100 days of BMT. Baseline echocardiograms were normal prior to admission and all patients were hospitalized and evaluated for left ventricular ejection fraction (LVEF), and New York Heart Association (NYHA) class. Patients with acute heart failure were treated with standard heart failure medications and patients post-BMT were treated with standard heart failure therapy plus adjuvant (IVIG) (500mg/Kg/day) for 48 hours. Baseline LVEF and NYHA class of 11 patients pre- and post-BMT were compared with LVEF and NYHA class of 14 patients with ADHF that did not receive a BMT. Results: The baseline diagnosis for all patients in the BMT group was NYHA class 4 and post-therapy improved to class 1.2. The baseline diagnosis for all patients in the non-BMT group were NYHA class 3.7 and improved to class 1.2 with medical therapy. The mean LVEF in the BMT group at diagnosis of ADHF was 27.5% and the mean post-therapy with IVIG was 57.6%. The mean baseline LVEF in the group not undergoing BMT and at diagnosis of ADHF was 28.2% and improved post-therapy to 45.2%. Conclusions: Acute decompensated heart failure in the cancer patient is highly treatable with aggressive medical management. Patients with ADHF after BMT and treated with IVIG may have potential clinical benefits with IVIG and standard medical therapy. Significant improvement in LVEF and NYHA were present in the BMT group versus the non-BMT group. These data suggest that BMT outcomes may be improved with routine heart failure management. Further randomized studies should be conducted.

[Table: see text]

No significant financial relationships to disclose.
Controlled study to evaluate physical and psychosocial effects of a standardized in-patient rehabilitation program for patients after allogenic stem cell transplantation
Authors: Bartsch H. , Auclair P. , Mumm A. , Weis J.
Published: March 2020

16519

Background: Allogeneic stem cell transplantation (HSCT) involves somatic restrictions as well as psychosocial problems. We devolped a specific, standardized in-patient rehabilitation program (RP) for pts after HSCT. Main goals of this combined medical and psychosocial RP are the accelerated increase of physical strength and the decrease of psychosocial distress to improve health related quality of life (QoL).The purpose of this study was to evaluate this RP and define prognostic factors to discriminate between groups of pts. who might differentially benefit by the program. Methods: 132 pts. after HSCT were prospectively enrolled in the treatment group and compared to 22 pts. after HSCT who did not receive the specific RP. Besides an elucidated medical and physical assessment all pts. answered different standadized questionaires for evaluation of treatment related symptoms, fatigue (MFI), QoL (QlQ), and psycosocial distress (HADS). All measurements were repeated at different time points. RP-Pts received the first questionnaire at their admission to our center, controls during the first control after HSCT at their respective treatment center (T1). T2 was at discharge from the hospital or four to six weeks after T1. T3 was six months and T4 twelve months after T2. A matched-pairs strategy was chosen to compare the smaller group of 22 control patients with matching partners selected from the treatment group. Results: The analyses reveal that the rehabilitation patients as a group had significant poorer initial values compared to controls, particularly in physical parameters and fatigue. At T2 and T3 both groups did improve significantly compared to T1 in different physical and psychosocial measures. However the matched pair analysis is still ongoing and data will be presented. Conclusions: Our data show that pts who are obviously more impaired following HSCT were preferentially transferred to our in-patient RP and benefit significantly from a standardized RP in physical as well as psychosocial conditions. The improvement increases over time and reaches after one year values comparable to those of healthy people.

No significant financial relationships to disclose.
Preoperative gemcitabine (G) and docetaxel (D) in patients (pts) with stage IB, II, or III non-small cell lung cancer (NSCLC): A phase II trial of the Minnie Pearl Cancer Research Network
Authors: Spigel D. R. , Hainsworth J. D. , Yardley D. A. , Burris H. A. , Thompson D. S. , Zubkus J. D. , Litchy S. , Silverberg D. , Thomas J. R. , Greco F. A.
Published: March 2020

17007

Background: Preoperative chemotherapy may improve outcomes for pts with resectable NSCLC compared with surgery alone. This multicenter community-based phase II trial examined the role of preoperative G/D for pts with resectable NSCLC. Methods: The primary endpoint was to assess the response rate (RR) of G/D in pts with potentially resectable clinical stages IB, II, and selected III NSCLC [T3N1, T1–3N2 (1 nodal station ≤2 cm), T4N0, T4N1 excluding vascular, tracheal, esophageal, vertebral disease, or malignant effusions]. Treatment included: D 30 mg/m2 IV and G 1000 mg/m2 IV D1,8 Q 21D × 3 cycles. Pts were restaged after treatment and resected 3–6 weeks later. Eligibility included: measurable disease, ECOG PS 0–1, adequate organ function, informed consent. Analysis was by intent to treat. Results: Fifty-four pts were enrolled between 4/04 and 9/05. Baseline features include: median age 62 years (42–82); male/female, 44%/56%; ECOG PS 0/1: 50%/50%; adenocarcinoma (28%), squamous (43%), large cell (9%), mixed/not specified (20%); IB (30%), IIA (5%), IIB (19%), IIIA (33%), IIIB (13%). Forty-eight pts (91%) completed preoperative treatment and 32 pts (60%) underwent resection. Grade 3/4 hematologic and non-hematologic toxicities were limited to neutropenia (20%) and infection (8%), respectively. All other toxicities were <5%. There were no treatment-related deaths. Complete/partial responses for all pts were observed in 1 pt/16 pts, respectively, for an overall RR of 31% (95% CI 20%–44%). Twenty-five pts (46%) had stable disease, and 11% had progression (6 pts were unevaluable.) No pathological complete responses were observed in 32 resected pts. After a median follow-up of 12 months, actuarial 1-year progression-free survival and overall survival (OS) are 54% and 79%, respectively. Median OS has not been reached. Conclusions: G/D is a well-tolerated preoperative regimen for pts with resectable NSCLC with activity rivaling platinum-based regimens. Further follow-up and additional studies comparing preoperative and adjuvant treatment are needed to assess the benefit of this regimen.

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NOV-002, a chemoprotectant/immunomodulator, added to first-line carboplatin/paclitaxel in advanced non-small cell lung cancer (NSCLC): A randomized Phase 1/2, open-label, controlled study
Authors: Pazoles C. J. , Gerstein H.
Published: March 2020

17021

Background: NOV-002 is a proprietary formulation of oxidized glutathione that modulates production of cytokines and hematopoietic growth factors. A randomized, multi-site advanced NSCLC trial conducted in the Russian Federation showed a one-year survival rate of 63% with NOV-002 + cytotoxic chemotherapy compared to 17% with cytotoxic chemotherapy alone. Methods: Forty-four chemotherapy-naïve, Stage IIIB/IV NSCLC patients (ECOG 0–2, stratified by disease stage) were randomized to one of three groups for six months of treatment: Groups A and B: NOV-002 in combination with carboplatin and paclitaxel (C+P). For each nominal 21-day chemotherapy cycle, these groups received 60 mg of NOV-002 i.v. daily for the first 4 days, then 60 mg i.m. (A) or s.c. (B) weekdays for the next 17 days. Group C: C+P alone. Initial doses of C and P in all three groups were 225 mg/m2 and AUC 6, respectively. Initiation of repeat C+P cycles required an absence of hematologic and other toxicities in excess of pre-defined values. Primary study endpoints included tumor response (scans performed at baseline and then every two months) and safety. Results: An intent-to-treat analysis of the best overall objective tumor response (WHO criteria), showed that 11 out of 16 (69%) Group B patients demonstrated greater than 50% tumor shrinkage versus 5 out of 15 (33%) in the control group (C) (p = 0.044, logistic regression stratified on disease stage). Six out of 13 (46%) patients in Group A demonstrated an objective response. 100% of NOV-002 treated patients in Group B and 85% in Group A were able to complete four cycles of C+P compared to 50% of control patients (Group C) (p = 0.004, chi square). NOV-002 was well-tolerated in this patient population. Conclusions: These data continue to suggest increased efficacy of NOV-002 plus cytotoxic chemotherapy compared to chemotherapy alone in advanced NSCLC.

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Impact of RASSF1A methylation on survival of stage IIIb and IV NSCLC patients treated with gemcitabine
Authors: Fischer J. R. , Ohnmacht U. , Rieger N. , Stoffregen C. , Manegold C. , Lahm H.
Published: March 2020

17028

Background: The epigenetic inactivation of genes plays an important role in lung cancer carcinogenesis. We have investigated the methylation status of seven genes (APC1A, DAPK, FHIT, p14ARF, p16INK4a, RARβ, RASSF1A) in serum DNA of NSCLC patients and analyzed their potential prognostic value. Methods: Blood samples were drawn pretherapeutically. Genomic DNA was purified from serum and subjected to sodium bisulfite treatment to convert unmethylated cytosine bases. Epigenetic alteration was detected by a nested methylation-specific PCR. Results: We have investigated a group of 92 patients with histologically confirmed NSCLC (60 males, 32 females; 21 stage IIIb, 71 stage IV; median age 60.9 years, range 34–78). All patients received gemcitabine first-line alone or in combination with other drugs. The vast majority of samples (n = 87) showed at least one methylated gene. More than half of the tested genes were hypermethylated in 20 samples (21.7%). The methylation frequencies of individual genes were 30.8% (APC1A), 26.1% (DAPK), 47.3% (FHIT), 30.4% (p14ARF), 25.9% (p16INK4a), 44.6% (RARβ) and 33.3% (RASSF1A). The hypermethylation status of none of the genes altered median overall survival (11.0 ± 1.4 mo) of the total population significantly. However, patients with a methylated RASSF1A gene who showed a partial response (n = 27) survived significantly longer (33.6 ± 10.4 mo) compared to those with a wild-type allele (16.1 ± 4.7 mo, P = 0.0045). This difference was not seen in patients with stable (n = 40) or progressive (n = 20) disease. Conclusions: Our results show that the hypermethylation frequency of single genes and the accumulation of epigenetic alterations in individual samples of NSCLC patients may vary considerably. Molecular parameters such as RASSF1A hypermethylation may be useful prognostic markers in subpopulations.

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Pemetrexed overcomes primary and secondary resistance to erlotinib in human non-small cell lung cancer (NSCLC) cell lines
Authors: Li T. , Ling Y. , Perez-Soler R.
Published: March 2020

17040

Background: Erlotinib (E) and pemetrexed (P) have proven single agent activity in advanced NSCLC after first-line chemotherapy. The presence of K-Ras or EGFR T790M mutations in NSCLC tumors has been associated with primary or secondary resistance to erlotinib. We have previously reported that sequential administration of P followed by E results in synergistic cytotoxicity in NSCLC cells that contain the wild-type EGFR gene. In this study, we evaluate the cytotoxic effects of E and P in E-resistant human NSCLC cell lines that have either EGFR or K-Ras mutations and validate predictive biomarkers for drug sensitivity. Methods: E-resistant NSCLC cell lines [H1650 (EGFRdel E746-A750), H1975 (EGFRL858R/T790M), and A549 (K-RasG12S)] were exposed to E and P continuously for 72 hrs. Combinations of E and P were compared with E or P alone. Cellular effects assayed include cell survival by cell count and MTT assay, cell cycle distribution and apoptosis by flow cytometry after propidium iodide staining, and expression of different elements of the EGFR axis by immunoblots. The degree of cytotoxic synergism was expressed by the combination index (C.I.). Results: P and E have significant cytotoxic synergism (C.I. <1) in these E-resistant NSCLC cell lines. The cytotoxic synergism is, at least in part, mediated by the inhibitory effect of E on the P-induced activation of EGFR-mediated proliferation and/or survival responses (mainly via the PI3K/AKT pathway). Sensitivity of NSCLC cells to P and E might be predicted by the ratio of (p-EGFR:EGFR) to (p-AKT:AKT), reflecting tumor dependency on the EGFR axis for growth and survival. Conclusions: Together with our previous data, we have demonstrated that the combination of P and E is synergistic in E-resistant NSCLC cell lines that have either a wild-type or mutant EGFR gene, or a mutant K-Ras gene. This combination deserves further evaluation in a clinical trial for the treatment of advanced NSCLC.

No significant financial relationships to disclose.
Tumor volume changes on serial imaging with megavoltage CT for non-small cell lung cancer during conformal radiotherapy
Authors: Siker M. L. , Tome W. A. , Mehta M. P.
Published: March 2020

17041

Background: Adaptive radiotherapy allows treatment plan modification based on data obtained during treatment. Assessing volume changes during treatment is now possible with intra-treatment imaging capabilities on radiotherapy devices. This study assesses non-small cell lung cancer (NSCLC) volume changes during treatment with conformal intensity-modulated radiotherapy by evaluating serial megavoltage CT (MVCT) scans. Methods: MVCTs were retrospectively reviewed for 25 patients treated with the TomoTherapy Hi-Art system at the University of Wisconsin. Twenty-one patients received definitive radiotherapy, 4 with extracranial stereotactic radioablation (60 Gy in 5 fractions) and 17 on a dose-per-fraction escalation protocol (57–80.5 Gy in 25 fractions). Four patients were treated palliatively (22–30 Gy in 8–10 fractions). Gross tumor volumes (GTVs) were contoured on serial MVCTs at weekly intervals, by individuals other than the treating physician, to minimize bias. Each patient had 3–25 scans including one at the beginning, mid-way, and one at the end of treatment. Initial GTVs ranged from 1.4 - 565.5 cm3 (mean = 70 cm3). Results: At completion of treatment, no patient demonstrated a complete response (CR). Partial response (PR) defined as a >65% decrease in tumor volume occurred in 3 (12%) and marginal response (MR) defined as a 35 - 65% reduction in tumor volume was noted in 5 (20%). The remaining 17 patients (68%) showed stable disease (SD) defined as <35% reduction or <40% increase in size. The minimum “scorable threshold” for volume discrepancy between scans to account for inter-scan assessment variability was set at >25% volume change; 10 patients (40%) had >25% tumor regression. None of the patients treated ablatively or palliatively showed tumor regression during treatment. Conclusions: Although gross tumor regression during treatment may be objectively measured using MVCTs, substantial volumetric decrease occurs only in a minority. The clinical significance of this regression is questionable, as there is no way to document histologic tumor clearance and therefore field reductions during radiotherapy cannot be recommended.

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