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Prognostic factors derived from recursive partition analysis (RPA) of radiation therapy oncology group (RTOG) brain metastases trials applied to surgically resected and irradiated brain metastatic cases

PURPOSEn(a) To identify the prognostic factors that determine survival after surgical resection and irradiation of tumors metastatic to brain. (b) To determine if the prognostic factors used in the recursive partition analysis (RPA) of brain metastases cases from Radiation Therapy Oncology Group (RTOG) studies into three distinct survival classes is applicable to surgically resected and irradiated patients.nnnMETHODnThe medical records of 125 patients who had surgical resection and radiotherapy for brain metastases from 1985 to 1997 were reviewed. The patients disease and treatment related factors were analyzed to identify factors that independently determine survival after diagnosis of brain metastasis. The patients were also grouped into three classes using the RPA-derived prognostic parameters which are: age, performance status, state of the primary disease, and presence or absence of extracranial metastases. Class 1: patients < or = 65 years of age, Karnofsky performance status (KPS) of > or =70, with controlled primary disease and no extracranial metastases; Class 3: patients with KPS < 70. Patients who do not qualify for Class 1 or 3 are grouped as Class 2. The survival of these patients was determined from the time of diagnosis of brain metastases to the time of death.nnnRESULTSnThe median survival of the entire group was 9.5 months. The three classes of patients as grouped had median survivals of 14.8, 9.9, and 6.0 months respectively (p=0.0002). Age of < 65 years, KPS of > or = 70, controlled primary disease, absence of extracranial metastases, complete surgical resection of the brain lesion(s) were found to be independent prognostic factors for survival; the total dose of radiation was not.nnnCONCLUSIONnBased on the results of this study, the patients and disease characteristics have significant impact on the survival of patients with brain metastases treated with a combination of surgical resection and radiotherapy. These parameters could be used in selecting patients who would benefit most from such treatment.

The relationship between biochemical failure and time to nadir in patients treated with external beam therapy for T1-T3 prostate carcinoma.

PURPOSE AND BACKGROUNDnTo determine a prostatic-specific antigen (PSA) nadir value and time to nadir that predict a high probability of freedom from biochemical failure in men treated with external beam therapy for prostate cancer.nnnMATERIALS AND METHODSnBetween January 1990 and March 1994, 228 men with T1-T3 adenocarcinoma of the prostate received a radical course of external beam irradiation with no prior or adjuvant hormonal therapy. All men had pre- and post-treatment serum PSA evaluations, and were followed up for at least 24 months, to ensure PSA nadir was reached. Biochemical failure was defined as three successive post-treatment rises in serum PSA, regardless of the magnitude of elevation.nnnRESULTSnOverall, 4-year biochemical disease-free survival (BDFS) was 42%. PSA nadir was predictive of subsequent BDFS. For those whose serum PSA nadir was < or =1 ng/ml, 4-year BDFS was 70%, versus 12% for those with serum PSA nadir > 1 ng/ml (P = < 0.001). The 4-year BDFS for patients with time to nadir < or =1 year, was 28%, versus 58% for those with time to nadir > 1 year (P < 0.001). For patients with PSA nadir < or =1 ng/ml, 4-year BDFS was 75% for those with time to nadir > 1 year, versus 61% for those with time to nadir < or =1 year (P < 0.021). In multivariate analysis, PSA nadir(< or =1 ng/ml versus >1 ng/ml, and time to nadir (< or =1 year versus > year) were independent predictors of BDFS alone with pre-treatment PSA and Gleason score.nnnCONCLUSIONnOnly those who achieved PSA nadir < or =1 ng/ml following external beam therapy have a favourable chance of lasting biochemical disease control, while those with nadir > 1 ng/ml have a high subsequent failure rate. The prognosis is better in patients with late time to nadir. In addition to PSA nadir, time to nadir, pretreatment PSA, and Gleason score were of independent prognostic significance.

A phase III study of high-dose intensification without hematopoietic progenitor cells support for patients with high-risk primary breast carcinoma.

Patients with more than nine ipsilateral lymph node involvement or inflammatory breast cancer have a 5-year survival rate of approximately 50%. We studied the efficacy of high-dose intensification, comparing it with the standard dose chemotherapy for patients with high-risk primary breast cancer. Patients with inflammatory breast cancer or more than nine ipsilateral lymph node involvement without evidence of distant metastasis were randomized to receive either standard dose 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) every 3 weeks for nine courses (control) or six courses of FAC followed by two courses of cyclophosphamide (5.25 g/m2), etoposide (1,500 mg/m2), and cisplatin (165 mg/m2) (HDCVP). The study was terminated in 1998 because of slow accrual of patients. Forty-six patients were entered in the study. At 4 years, the overall survival was 72.8% (SE 11.9%) and 61.7% (SE 12.4%), and disease-free survival were 45.5% (SE 12.3%) and 33.7% (SE 11.9%) for the control and HDCVP groups, respectively (p = 0.757 and 0.720). With the small number of patients in our study, a small overall survival benefit of high-dose intensification compared with the standard therapy cannot be excluded. However, any substantial benefit is unlikely.

Concurrent chemotherapy with hyperfractionated accelerated thoracic irradiation in stage III non-small cell lung cancer

OBJECTIVESnWe evaluated the effect of hyperfractionated accelerated radiotherapy combined with low dose radiosensitisers followed by standard dose chemotherapy in the treatment of unresectable stage III non small cell lung cancer (NSCLC).nnnMETHODSnForty-seven patients received thoracic radiotherapy (1.5 bid x 5 days x 4 weeks) in combination with low dose daily (3-6 mg/m2) cisplatin +/- weekly vinblastine chemotherapy (step I), followed by three cycles of standard dose chemotherapy alone consisting of cisplatin (75-80 mg/m2) and vinblastine (8-16 mg/m2) given at 3-4 week intervals (step II).nnnRESULTSnThe overall response rate was 70% (21% CR). The progression free interval and the median survival duration were 10.4 months and 17.3 months, respectively. The 3 year survival rate was 21%. The site of first progression was local in 44%, distant in 41%, and simultaneous in 15% of patients. Levels of esophageal toxicity were significant but acceptable with the use of prophylactic therapy. Grade 3 or 4 esophageal toxicity was observed in 28 and 19% of patients during step I and II of the study, respectively. There were three deaths associated with esophageal toxicity. All occurred prior to the implementation of the prophylactic therapy for esophagitis. Acute pulmonary symptoms were reported in 25% of patients in step I, and pulmonary fibrosis, primarily asymptomatic, was observed in 51% of patients. Hematological toxicity was moderate. Two patients died of neutropenic sepsis/pneumonia.nnnCONCLUSIONnConcurrent chemotherapy and hyperfractionated accelerated radiotherapy followed by chemotherapy appears moderately effective in controlling tumour growth as measured by response rates and survival estimates. Toxicity is considerable but manageable and compatible with results from other combined modality studies.

Comparison of Favorable Early-Stage Hodgkin's Lymphoma Treatments: A Single-Institution Review

PURPOSEnTo compare outcomes of patients receiving combined-modality chemotherapy and radiation (CMT) vs. other approaches for early-stage Hodgkins lymphoma (HL).nnnMETHODS AND MATERIALSnA review of patients with nonbulky, early-stage (IA/IIA) HL treated between 1984 and 2002 was performed to determine the treatment approaches used and the outcomes obtained.nnnRESULTSnThere were 173 adult patients with newly diagnosed early-stage HL (49% men, 51% women, median age 33 [range 17-82] years). Treatment was as follows: extended-field radiotherapy alone (EFRT) 49%; chemotherapy alone (CTA) 13%; and CMT 38%. Among CMT patients, 36% received abbreviated doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy (three to four cycles) followed by involved-field radiotherapy. With a median follow-up of 8.3 years, the estimated 10-year relapse-free survival (RFS) and overall survival (OS) rates for the entire cohort were 78% and 85%, respectively. The 10-year RFS and OS rates for the various groups were as follows: 69% and 81% for EFRT; 78% and 84% for CTA; and 87% and 89% for CMT. The 10-year RFS rate was significantly higher (p < 0.01) among CMT patients. The use of EFRT has diminished from approximately 90% in the 1980s to virtually no use at present, whereas the use of CTA and CMT has increased significantly (p < 0.01).nnnCONCLUSIONnEarly-stage HL treatment has changed dramatically over the past 2 decades, and our results support the superiority and continued use of CMT, specifically abbreviated-course chemotherapy and involved-field radiotherapy, as an appropriate treatment approach.

Age-not Charlson Co-morbidity Index-predicts for mortality after stereotactic ablative radiotherapy for medically inoperable stage I non-small cell lung cancer

Purpose In this single institution retrospective study of patients with stage I medically inoperable non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR) we attempt to model overall survival (OS) using initial prognostic variables with specific attention on the Charlson co-morbidity index (CCI). Methods Between 2008 and 2013, 335 patients with medically inoperable stage I NSCLC were treated with SABR or hypofractionated radiotherapy (50–60 Gy in at least 5 Gy or 4 Gy fractions respectively) at our institution. Medical comorbidities and Charlson scores were determined by individual chart review. Patients were stratified into 3 groups based on the CCI score (0–1, 2–3, 4–9) and again based on the age-adjusted Charlson Comorbidity score (aCCI). Cumulative survival for each stratum was determined using the Kaplan-Meier method. Non-significant and confounding variables were identified and discounted from survival modeling. 3 sex stratified Cox regression models were tested: (1) aCCI with age and comorbidity combined; (2) age and CCI; (3) age alone, comorbidity removed. Results The median survival was 4.4 years and the median follow up 4.7 years. The median CCI and aCCI scores were 2 and 5 respectively. Patients with aCCI 7–12 had an increased hazard of death on univariate analysis HR 2.45 (1.15–5.22 95%CI, p = 0.02) and -excluding age as a competing variable- on multivariate analysis HR 2.25 (1.04–4.84 95%CI, p = 0.04). Patients with CCI 4-9 had an increased hazard of death on univariate analysis HR 1.57(1.30–2.90) but not on multivariate analysis. On formalized testing – with either continuous or categorical variables- all three survival models yielded similar coefficients of effect. Conclusion We identify male gender, weight loss greater than 10% and age as independent prognostic factors for patients treated with medically inoperable NSCLC treated with SABR or hypofractionated radiotherapy. Based on our survival models, age alone can be used interchangeably with aCCI or CCI plus age with the same prognostic value. Age is more reliably recorded, less prone to error and therefore a more useful metric than Charlson score in this group of patients.

PO-0667: Second malignancies after TBI in AHCT for relapsed follicular lymphoma

Material and Methods: Data from a clinical phase-II trial using LDRT for palliation in diffuse large B-cell lymphoma (DLBCL) patients were compared with clinical outcome of patients with follicular lymphoma (FL), marginal zone lymphoma (MZ), and mycosis fungoides (MF) which were treated with LDRT at our Institution in the same period. LDRT consisted of 4 Gy in 2 fractions on symptomatic areas only for both DLBCL and indolent NHLs. Bulky disease was defined as > 5 cm in maximum diameter. Chemoresistance was defined as the failure of chemo to achieve a complete or partial response, or as disease relapse after a complete response. Clinical response was assessed 21 days after LDRT, and was defined as reduction > 50% of maximum diameter of the radiated lesions. Response evaluation was performed with CT-scan or clinical exam for palpable lesion. Toxicity was scored using the CTCAE v3.0.

236: Validity of Specific Growth Rate in Stage I Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiotherapy (SBRT)

CARO 2016 _________________________________________________________________________________________________________ concentration of the metabolite in the cancer group (p = 0.040). Subsequently, EBC samples were analyzed by an LC-QTOF-Mass Spectroscopy (MS) using a non-targeted approach. A total of 625 compounds were detected in all EBC samples combined among which, four were up regulated in patients with lung cancer (TTest, p < 0.05). Conclusions: Lower concentrations of methanol (EBC), glycoprotein (sputum), absence of glucose in sputum identified through MRS and up regulation of four specific metabolites in EBC identified through MS in patients with known lung cancer suggest that MRS and MS may provide a lung cancer specific metabolic profile that can be used to develop a non-invasive tool to screen for lung cancer in high-risk population.