In lung cancer, randomized trials assessing hyperfractionated or accelerated radiotherapy seem to yield conflicting results regarding the effects on overall (OS) or progression-free survival (PFS). ...The Meta-Analysis of Radiotherapy in Lung Cancer Collaborative Group decided to address the role of modified radiotherapy fractionation.
We performed an individual patient data meta-analysis in patients with nonmetastatic lung cancer, which included trials comparing modified radiotherapy with conventional radiotherapy.
In non-small-cell lung cancer (NSCLC; 10 trials, 2,000 patients), modified fractionation improved OS as compared with conventional schedules (hazard ratio HR = 0.88, 95% CI, 0.80 to 0.97; P = .009), resulting in an absolute benefit of 2.5% (8.3% to 10.8%) at 5 years. No evidence of heterogeneity between trials was found. There was no evidence of a benefit on PFS (HR = 0.94; 95% CI, 0.86 to 1.03; P = .19). Modified radiotherapy reduced deaths resulting from lung cancer (HR = 0.89; 95% CI, 0.81 to 0.98; P = .02), and there was a nonsignificant reduction of non-lung cancer deaths (HR = 0.87; 95% CI, 0.66 to 1.15; P = .33). In small-cell lung cancer (SCLC; two trials, 685 patients), similar results were found: OS, HR = 0.87, 95% CI, 0.74 to 1.02, P = .08; PFS, HR = 0.88, 95% CI, 0.75 to 1.03, P = .11. In both NSCLC and SCLC, the use of modified radiotherapy increased the risk of acute esophageal toxicity (odds ratio OR = 2.44 in NSCLC and OR = 2.41 in SCLC; P < .001) but did not have an impact on the risk of other acute toxicities.
Patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy; a similar but nonsignificant trend was observed for SCLC. As expected, there was increased acute esophageal toxicity.
Abstract
Introduction: HER2 gene amplificationis associated with shorter disease-free and overall survival in breast cancer.The prognostic value of the NLR, PLR, LMR or MLR has been also reported for ...many types of cancer. The aim of the present study was to assess the blood the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) as a prognostic factors in breast cancer patients (BC) according to HER2 overexpression. Material and Methods: A the retrospective analysis of 529 BC patients who were treated at COI (Gliwice, Poland) between January 2005 and June 2018 was performed. The prognostic value (OS) of the pre-treatment PLR, NLR and MLR was assessed by univariate and multivariate analysis. The cut-off values were determined using receiver operating characteristic curves. Based on the cut-off values determined, the NLR was considered as ‘elevated’ at >1.68, the MLR value was ‘elevated’ at >0.23 and the PLR was considered ‘elevated’ at>119.0. Result: The 5-year OS rates in HER2 positive and HER2 negative BC were 86.5 and 90.4%, respectively.The 5-year OS in the NLR >1.68 subgroup with HER2 (83.0 vs. 93.0%; P=0.579) and without HER2 overexpression (88.7 vs. 92.9%; P=0.159) were lower compared with a patients with NLR <1.68. Similarly, 5-year OS was lower in patients with a PLR of >119.0 with HER2 (85.9vs. 87.8%; P=0.782) and without HER2 overexpression (88.1 vs. 94.0%; P=0.060) compared with that in patients with a PLR of ≤119.0. The 5-year OS was similar in patients with a MLR of >0.23 with HER2 overexpression compared with that in patients with a MLR of ≤119.0 (86.1 vs. 86.7%; P=0.745). In group with a MLR of >0.23 without HER2 overexpression OS was lower compared with that in patients with a MLR of ≤0.23 (89.5 vs. 91.7%; P=0.185). Univariate Cox regression analyses of OS showed that in subgroup with HER2 overexpression factors such as tumor size (T3-4 vs. T1-2, HR=2.47; P=0.008), the presence of lymph node metastases (N+ vs.N0, HR=3.15; P=0.006) and estrogen receptor status (ER(+) vs. ER(-), HR=0.50; P=0.039) were statistically significant. Factors such as NLR, PLR and MLR were not statistically significant.Multivariate analysis revealed that in group breast cancer patients with HER2 overexpression negative prognostic factors were: tumor size and lymph node metastases. In contrary, positive prognostic factor was positive steroid receptor status (ER+).Univariate Cox regression analyses of OS showed that in subgroup without HER2 overexpression factors such as tumor size (T3-4 vs. T1-2, HR=3.89; P=0.0001), the presence of lymph node metastases (N+ vs.N0, HR=3.16; P=0.001), tumor grade (G3 vs. G1-2, HR=2.59; P=0.005), estrogen receptor status (ER(+) vs. ER(-), HR=0.43; P=0.012), progesterone receptor status (PR(+) vs. PR(-), HR=0.31; P=0.001), leukocytes >6.22 (HR=2.11; P=0.041), monocytes >0.52 (HR=2.24; P=0.018) and PLT>291 (HR=2.24; P=0.024) were statistically significant. Factors such as NLR (HR=1.66; P=0.166), PLR (HR=2.03; P=0.067) and MLR (HR=1.61; P=0.192) were not statistically significant. Multivariate analysis revealed that significant negative prognostic factors in without HER2 overexpression breast cancer patients were: tumor size, lymph node metastases and leukocyte number. In contrary, positive prognostic factor were positive steroid receptor status (PR+) and lymphocytes number. Conclusion: Elevated PLR, NLR and MLR worsens insignificantly prognosis in group of patients with tumors without HER2 overexpression. The presence of elevated MLR, PLR, NLR did not influence overall survival (prognosis) in group with HER2 overexpression. In both subgroups (HER2 positive and HER2 negative) common negative prognostic factors were tumor size and lymph node metastases.
Citation Format: Joanna Huszno, Zofia Kolosza, Jolanta Mrochem Kwarciak, Aleksander Zajusz. Prognostic value of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratio breast cancer patients according to HER2 overexpression abstract. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-67.
Abstract Aim To evaluate the tolerability and toxicity of PCI in patients with NSCLC. Background Prophylactic cranial irradiation (PCI) is a standard treatment for patients with small cell lung ...cancer. There are data showing a decreasing ratio of brain metastases after PCI for non-small cell lung cancer (NSCLC-non small cell lung cancer) patients but, so far, there is no evidence for increasing overall survival. The main concern in this setting is the tolerance and toxicity of the treatment. Materials and methods From 1999 to 2007, 50 patients with NSCLC treated with radical intent underwent PCI (30 Gy in 15 fractions). Mean follow-up was 2.8 years. The tolerability and hematological toxicity were evaluated in all patients, a part of participants had done neuropsychological tests, magnetic resonance imaging with1 H nuclear magnetic resonance spectra, and estimation of pituitary function. Results During follow-up, 20 patients developed distant metastases, 4-brain metastases. Fourteen (30%) patients had acute side effects: (headache, nausea, erythema of the skin). The symptoms did not require treatment breaks. Six patients complained of late side effects (vertigo, nausea, anxiety, lower extremity weakness, deterioration of hearing and olfactory hyperesthesia). Hematological complications were not observed. Testosterone levels tended to decrease ( p = 0.062). Visual-motor function deteriorated after treatment ( p < 0.059). Performance IQ decreased ( p < 0.025) and the difference between performance IQ and verbal IQ increased ( p < 0.011). Degenerative periventricular vascular changes were observed in two patients. Analysis of the spectroscopic data showed metabolic but reversible alterations after PCI. Conclusion PCI in the current series was well tolerated and associated with a relatively low toxicity.
Abstract The aim of study was to assess the tolerance and effectiveness of preoperative chemoradiotherapy in the group of 40 patients with operable gastric cancer. The therapy was well tolerated. We ...observed the high rate of pathological response and R0 resections, low rate of local recurrence and high percent of 2-year survival.
Clinical data that compare external-beam radiotherapy (EBRT) combined with high-dose-rate brachytherapy (HDR-BT) boost versus EBRT alone are scarce. The analysis of published studies suggest that ...biochemical relapse-free survival in combined EBRT and HDR-BT may be superior compared to EBRT alone. We retrospectively examined the effectiveness and tolerance of both schemes in a single center study.
Between March 2003 and December 2004, 229 patients were treated for localized T1-T2N0M0 prostate cancer. Median age was 66 years (range, 49 - 83 years). PSA level ranged from 0.34 to 64 ng/ml (median 12.3 ng/ml) and Gleason score ranged from 2 to 10. The analysis included 99 patients who underwent EBRT with HDR-BT (group A) and 130 patients who were treated with EBRT alone (group B).
Median follow-up was 6 years. Biochemical relapses occurred in 34% vs. 22% (p = 0.002), local recurrences in 17% vs. 5% (p = 0.002), and distant metastases in 11% vs. 6% (p = 0.179) of patients in groups A and B, respectively. Five-year biochemical relapse-free survival was 67% vs. 81% (p = 0.005), local recurrence-free survival 95% vs. 99% (p = 0.002), metastases-free survival 95% vs. 94% (p = 0.302) for groups A and B, respectively. Five-year overall survival was 85% in both groups (p = 0.596). Grade 2/3 late GI complications appeared in 9.2% and 24.8% (p = 0.003), respectively. Grade 2/3 late GU symptoms occurred in 12% in both groups.
Although because of the retrospective character of the study and nonrandomized selection of fractionation schedule the present conclusions had limitations EBRT alone appeared more effective than EBRT combined with HDR-BT. It was likely the result of the less frequent use of androgen deprivation therapy (ADT) for combined scheme group, too low dose in a single BT fraction or inadequate assumptions regarding fractionation sensitivity of prostate cancer.
Two different radiotherapy techniques, a traditional one (CRT) - based on consecutive decreasing of irradiation fields during treatment, and intensity modulated radiation therapy technique (IMRT) ...with concomitant boost, deliver different doses to treated volumes, increasing the dose in regions of interest. The fractionation schedule differs depending on the applied technique of irradiation. The aim of this study was to compare different fractionation schedules considering tumor control and normal tissue complications. The analysis of tumor control probability (TCP) and normal tissue complication probability (NTCP) were based on the linear quadratic (LQ) model of biologically equivalent dose. A therapeutic gain (TG) formula that combines NTCP and TCP for selected irradiated volumes was introduced to compare CRT and simultaneous boost (SIB) methods. TG refers to the different doses per fraction, overall treatment time (OTT), and selected biological factors such as tumor cell and repopulation time. Therapeutic gain increases with the dose per fraction and reaches the maximum for the doses at about 3 Gy. Further increase in dose per fraction results in decrease of TG, mainly because of the escalation of NTCP. The presented TG formula allows the optimization of radiotherapy planning by comparing different treatment plans for individual patients and by selecting optimal fraction dose.
We sought to evaluate the efficacy, biochemical effects, safety and outcome of recombinant human thyroid-stimulating hormone (rhTSH) as an adjunct to radioiodine treatment of advanced differentiated ...thyroid carcinoma (DTC). We also sought to determine whether rhTSH is useful as an adjunct to radioiodine treatment following isotretinoin re-differentiation therapy of DTC metastases that have lost function. Therefore, in 54 consecutive patients who had retained bulky metastatic and/or locoregional lesions of DTC despite the exhaustion of other therapeutic options, we gave one to four courses of two consecutive daily intramuscular injections of rhTSH, 0.9 mg, followed by a therapeutic activity of (131)I per os on day 3. Fifty patients had received prior radioiodine treatment aided by l-thyroxine (T(4)) withdrawal. We included in the study 23 patients who had received a trial of isotretinoin therapy for re-differentiation of confirmed de-differentiated metastases. In a blinded, within-patient comparison of post-therapy whole-body scans after the first rhTSH-aided and latest withdrawal-aided treatments in patients with functional metastases at baseline, 18 of 27 (67%) scan pairs were concordant, four (15%) were discordant in favour of the rhTSH-aided scan and five (19%) were discordant in favour of the withdrawal-aided scan. In total, 37 (74%) of 50 paired scans were concordant, eight (16%) favoured rhTSH and five (10%) favoured withdrawal. All differences appeared to be attributable to clinical causes, not to any difference between endogenous and exogenous TSH stimulation. Reflecting the biochemical activity of rhTSH and the release of thyroglobulin (Tg) due to tumour destruction, median serum Tg concentration rose approximately fourfold between baseline and day 6 of the rhTSH-aided treatment course. rhTSH was well tolerated, with mostly minor, transient toxicity, except for neck oedema in three patients with neck infiltrates and pathological spine fracture in one patient with a large vertebral metastasis. At 6 months, complete response occurred in one (2%), partial response in 12 (26%) and disease stabilisation in 19 (40%) of 47 evaluable patients. The rate of complete + partial response was 41% and that of disease stabilisation, 30%, in the 27 evaluable patients with functional metastases at baseline; the corresponding rates were 10% and 55% in the 20 evaluable patients with non-functional metastases at baseline. Although within-patient comparison of early outcome after both modalities is limited by a significantly greater median number of courses and a greater median cumulative activity of radioiodine given under withdrawal, response to rhTSH-aided and withdrawal-aided treatment was similar in 23 (52%) of 44 evaluable patients, superior with rhTSH in 12 (27%) and superior with withdrawal in seven (16%). In two patients, a superior response was obtained after isotretinoin pretreatment and rhTSH and attributed to re-differentiation therapy. In conclusion, our study provides preliminary evidence that rhTSH safely and effectively aids radioiodine treatment of advanced DTC, and does so to an at least equivalent degree as does T(4) withdrawal.
Purpose. Toxicity of an accelerated 7 days per week fractionation schedule (arm A) was evaluated and compared with a conventional 5 days per week treatment (arm B) in a randomized trial.
Materials ...and methods. Forty-four patients with squamous cell carcinoma of the head and neck in stage T
2–4N
0–1M
0 were included in the study. Total dose and dose per fraction of 2.0 Gy given once-a-day at 24 h intervals were the same in both arms of the trial. The only difference was the overall treatment time being 5 weeks in arm A and 7 weeks in arm B.
Results. Analysis of severe mucosal reactions shows significant difference between arm A and B, with regard to both maximum score and duration of severe mucositis. Confluent mucositis (score > 15 according to the Dische system) lasting longer than 3 weeks developed in 48% of patients in arm A and only in 5% in arm B. In group A seven (30%) late effects (osteo- and soft tissue necrosis) occurred during 7–12 month follow-up with two reactions (10%) in group B being suspected as late effects. There was significant association between acute reactions and late effects in arm A, suggesting that the late effects are consequential.
Conclusion. The high incidence of severe acute reactions and consequential late effects suggests that the accelerated treatment in arm A (using daily fractions of 2.0 Gy, 7 days per week) gives unacceptable toxicity.
The purpose of the study is the evaluation of the efficacy and morbidity of conformal radiotherapy in patients with clinical stage T1-T3 prostate cancer.
The study group comprises 71 patients with ...clinical stage T1-T3, N0, M0 prostate cancer, treated with conformal radiotherapy between 1998 and 2000. The planned target volume included in all patients prostate a margin (PTV1). Forty patients (56%) were initially irradiated for the pelvic region (PTV2). The mean total radiation dose delivered to prostate was 68 Gy, and to the pelvis--44 Gy. Radiation morbidity was scored by the RTOG/EORTC system, and it was analysed in relation to the total dose. The 2-year biochemical relapse-free survival and 2-year metastatic control rates were compared by clinical T-stage and histologic grade. The probability of biochemical relapse and the probability of distant metastases were estimated as a function of clinical T-stage, histologic grade, the planned target volume (PTV1 vs PTV1+PTV2) and total radiation dose.
There were no acute > or = grade III bladder toxicity, and only 3 patients (4%), who were irradiated for the pelvis had acute grade III bowel toxicity. No patient had late grade > or = III toxicity. The actual 2-year biochemical relapse-free survival and 2-year metastatic control according to T-stage were respectively: T1c--89% and 100%, T2a--90% and 100%, T2b--77% and 85%, T2c--62% and 83%, T3--58% and 65%, and by histologic grade they were respectively: G1--100% and 100%, G2--79% and 96%, G3--36% and 50%. Statistically significant relationships were found between the probability of distant metastases or biochemical relapse and histologic grade (p<0.00, p=0.005). Clinical T-stage had significant influence on the probability of distant metastases and borderline influence on the probability of biochemical relapse (p=0.004 and p=0.056). In the multivariate analysis, only histologic grade remained significant.
Conformal radiotherapy for prostate cancer is well tolerated, and it yields satisfactory results which depend on histologic grade and clinical T-stage.
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