The influence of time of radio-chemotherapy and other therapeutic factors on treatment results in patients with limited disease small cell lung cancer.

PURPOSE: The evaluation of effect of therapeutic parameters such as time of starting thoracic radiotherapy in relation to chemotherapy, schedule of combination chemo- and radiotherapy and SER, on treatment results in patients with limited disease small cell lung cancer (LD SCLC). METHODS: Between 2000 and 2007, 212 patients with LD SCLC received combined therapy: chemotherapy and thoracic radiotherapy. All patients received chemotherapy according to PE schedule (4-6 cycles), in combination with thoracic radiotherapy. The total dose applied to GTV was 54 Gy given in 27-30 fractions using fraction dose of 1.8-2.0 Gy. The concurrent treatment was performed in 112 patients (52.8%): the conventional fractionation (once a day, every five days a week) in 35 patients while 77 patients received "moderate" accelerated fractionation (one fraction a day, every four days a week and two fractions within one day, a week apart, with 6h gap). The remaining 100 patients (47.2%) received sequential treatment. The time from the first day of chemotherapy to the end of thoracic radiotherapy (SER) was evaluated in all patients. The SER ranged from 57 to 337 days with the median value of 121 days. RESULTS: The complete response in the thorax was observed in 143 out of 212 patients (67.5%). Out of these, 82 patients received concurrent chemo-radiotherapy (given in 22 patients as conventional dose fractionation and in 60 patients according to "moderate" accelerated dose fractionation), and the remaining 61 patients were treated with sequential therapy. The 5-year survival rates were: 17.7% for overall survival (OS), and 19.3% for disease-free survival (DFS). The relationship of therapeutic factors to survival rates showed statistically significant improvement of survival ratios in relation to early starting of thoracic radiotherapy and application of concurrent chemo-radiotherapy. The results of logistic regression revealed significant relationship between the value of SER and OS and DFS. The analysis shows that each day of extension of the SER resulted in increased probability of death (decrease of OS) by 0.28% and in increased the risk of development failure (decrease of DFS) by 0.31%. The influence of SER on lowered probability of complete response frequency was not statistically significant. CONCLUSIONS: The concurrent chemo-radiotherapy with early administration of thoracic radiotherapy, results in improved complete response in the thorax and increase of overall and disease-free survival rates. The 5-year survival rates were: 17.7% for overall survival and 19.3% for disease-free survival. Our analysis and data from the literature suggest that shorter SER may play prognostic role in patients with LD SCLC treated with combination chemo- and radiotherapy. However, these observations require the confirmation in following studies.

Gefitinib plus cisplatin and radiotherapy in previously untreated head and neck squamous cell carcinoma: a phase II, randomized, double-blind, placebo-controlled study.

BACKGROUND AND PURPOSE: To assess the efficacy and safety of gefitinib given concomitantly and/or as maintenance therapy to standard cisplatin/radiotherapy for previously untreated, unresected, stage III/IV non-metastatic SCCHN. MATERIALS AND METHODS: In this phase II, double-blind, study, 226 patients were randomized to gefitinib 250mg/day, 500mg/day or placebo in two phases: a concomitant phase (gefitinib or placebo with chemoradiotherapy), followed by a maintenance phase (gefitinib or placebo alone). Primary endpoint was local disease control rate (LDCR) at 2years; secondary endpoints were LDCR at 1year, objective response rate, progression-free survival, overall survival, and safety and tolerability. RESULTS: Gefitinib (250 and 500mg/day) did not improve 2-year LDCR compared with placebo either when given concomitantly with chemoradiotherapy (32.7% vs. 33.6%, respectively; OR 0.921, 95% CI 0.508, 1.670 [1-sided p=0.607]) or as maintenance therapy (28.8% vs. 37.4%, respectively; OR 0.684, 95% CI 0.377, 1.241 [1-sided p=0.894]). Secondary efficacy outcomes were broadly consistent with the 2-year LDCR results. In both doses, gefitinib was well-tolerated and did not adversely affect the safety and tolerability of concomitant chemoradiotherapy. CONCLUSION: Gefitinib was well-tolerated, but did not improve efficacy compared with placebo when given concomitantly with chemoradiotherapy, or as maintenance therapy alone.

Comparison of the effectiveness of "late" and "early" prophylactic cranial irradiation in patients with limited-stage small cell lung cancer.

PURPOSE: To evaluate the effectiveness of timing of application of prophylactic cranial irradiation (PCI) in patients with small cell lung cancer in limited stage of disease (LS SCLC). PATIENTS AND METHODS: Between 1995 and 2004, 129 patients with LS SCLC were treated within two consecutive phase II studies assessing different schedules of combined treatment. All patients received chemotherapy and concurrent thoracic radiotherapy. In 86 patients (66.7%) who developed complete response in the thorax, PCI was performed either after chemoradiotherapy ("late" PCI , n = 45 [52.4%]) or during chemoradiotherapy ("early" PCI, n = 41 [47.7%]). In the latter case, PCI was given immediately after the end of thoracic radiotherapy and prior to the last cycles of chemotherapy to a total dose of 30 Gy in 2-Gy fractions to the whole brain. The results were evaluated with regard to 4-year rates of overall survival, disease-free survival, and brain metastases-free survival. Additionally, the prognostic role of PCI application and its time delay in relation to survival rates and incidence of brain metastases was estimated. RESULTS: The 4-year survival rates were 25.5% for overall survival, 26.8% for disease-free survival, and 67.8% for brain metastases-free survival. During the observation period, 32 patients (24.8%) developed brain metastases, which occurred in 20 of 43 patients (46.5%) without and only in twelve out of 86 patients (14%) with PCI. The 4-year brain metastases-free survival rates were 81.8%, if PCI was applied, versus 32.2%, if no such procedure was used (for p = 0.0000). The timing of PCI appeared to be an important factor in terms of decreasing the incidence of brain metastases. CONCLUSION: PCI significantly decreases the incidence of brain metastases and delays their development in patients with LS SCLC. "Early" PCI is more effective than PCI applied after combined therapy.

Thymoma: Results of treatment and role of radiotherapy.

PURPOSE: The aim of this study is to assess results of treatment, factors influencing prognosis with regard to causes of failure and treatment tolerance in patients with thymoma. MATERIAL AND METHODS: Between 1966 and 2006, 63 patients with thymoma had been treated at the Centre of Oncology in Krakow. Patients were treated by means of different treatment modalities: surgery followed by radiotherapy (52%), radiotherapy alone (13%), chemoradiotherapy alone (15%), surgery followed by chemoradiotherapy (5%), surgery alone (5%) and others. RESULTS: The 10-year locoregional recurrence-free survival (LRRFS) was 79%, disease free survival (DFS) was 57% and overall survival (OS) was 57%. Masaoka stage was the only independent prognostic factor for LRRFS. Masaoka stage and method of radiotherapy delivery (higher photon energies), were independent prognostic factors for OS. For DFS, the independent prognostic factors were age, type of treatment (favoured surgery followed by radiotherapy or chemoradiotherapy), Masaoka stage and year of start of treatment. Most common reactions were lung fibrosis in 36% of patients (mainly asymptomatic in most patients), pneumonitis (9%) and oesophagitis (4%). CONCLUSIONS: Surgery combined with radiotherapy and chemoradiotherapy and modern radiotherapy techniques are correlated with improvement of survival in patients with early stage thymoma.

Comparison between intensity modulated radiotherapy (IMRT) and 3D tangential beams technique used in patients with early-stage breast cancer who received breast-conserving therapy.

BACKGROUND: The most often found complications in patients with breast cancer who received radiotherapy are cardiac and pulmonary function disorders and development of second malignancies. AIM: To compare the intensity modulated radiotherapy with the 3D tangential beams technique in respect of dose distribution in target volume and critical organs they generate in patients with early-stage breast cancer who received breast-conserving therapy. MATERIALS AND METHODS: A dosimetric analysis was performed to assess the three radiotherapy techniques used in each of 10 consecutive patients with early-stage breast cancer treated with breast-conserving therapy. Radiotherapy was planned with the use of all the three techniques: 3D tangential beams with electron boost, IMRT with electron boost, and intensity modulated radiotherapy with simultaneous integrated boost. RESULTS: The use of the IMRT techniques enables more homogenous dose distribution in target volume. The range of mean and median dose to the heart and lung was lower with the IMRT techniques in comparison to the 3D tangential beams technique. The range of mean dose to the heart amounted to 0.3-3.5 Gy for the IMRT techniques and 0.4-4.3 for the tangential beams technique. The median dose to the lung on the irradiated side amounted to 4.9-5 Gy for the IMRT techniques and 5.6 Gy for the 3D tangential beams technique. CONCLUSION: The application of the IMRT techniques in radiotherapy patients with early-stage breast cancer allows to obtain more homogenous dose distribution in target volume, while permitting to reduce the dose to critical organs.

Tracheal cancer: Role of radiation therapy.

PURPOSE: To assess the results of tracheal cancer patients treatment and factors influencing prognosis. BACKGROUND: Primary malignant neoplasms of the trachea are rare. The treatment of choice for tracheal carcinomas is resection. Radiation therapy is recommended as a part of radical treatment or for palliation of symptoms. MATERIALS AND METHODS: Between 1962 and 2006, 50 patients diagnosed with tracheal cancer were treated at the Centre of Oncology in Krakow. The analysis focused on locoregional recurrence-free survival (LRRFS), disease free survival (DFS) and overall survival (OS). Survival rates, univariate and multivariate analyses of prognostic factors were performed using the Kaplan-Meier method, the log rank test and Cox's proportional hazard method, respectively. For over 40 years, patients were treated using different modalities: surgery followed by radiotherapy (6%), radiotherapy (78%), chemoradiotherapy (8%), and symptomatic treatment (8%). RESULTS: The 5-year LRRFS was 18%, DFS was 15% and OS was 17%. gender (favoured females) was the only prognostic factor for LRRFS. For OS, the independent prognostic factors were performance status (favoured Karnofsky higher than 80), stage and year of start of the treatment (later than 1988 vs. earlier - 5-year OS 20% vs. 12%). 5-year OS in the following (strongly differentiated over the time) treatment modalities were: surgery followed by radiotherapy (66%), radiotherapy (16%), chemoradiotherapy (0%), and symptomatic treatment (0%). Of 44 patients treated with radiotherapy symptomatic partial response was observed in 32 patients and follow-up imaging studies revealed complete response in 5 patients, partial response in 25, stable disease in 4 or progressive disease in 4. CONCLUSIONS: Radical treatment in patients in early stage and good performance status seems to be correlated with the improvement of survival. However, despite the fact that results of treatment are poor, radiotherapy offers symptomatic improvement.

ProGRP and NSE in therapy monitoring in patients with small cell lung cancer.

The usefulness of serum pro-gastrin-releasing peptide (ProGRP) as a tumor marker in patients with small cell lung cancer has recently drawn the attention of many research centers. The aim of the study was the evaluation of ProGRP, neuron-specific enolase (NSE), soluble fragment of cytokeratin 19 (CYFRA 21-1) and lactate dehydrogenase (LDH) levels at the time of diagnosis and during chemo- and radiotherapy of small cell lung cancer patients with limited disease (SCLC-LD). The studies were performed on a group of 64 patients with SCLC-LD who had received no prior therapy. All the patients were given the same treatment regimen. ProGRP, NSE, CYFRA 21-1 and LDH were measured before each course of chemotherapy and then at 3 and 6 months after the end of treatment. Prior to therapy, elevated levels of ProGRP, NSE, CYFRA 21-1 and LDH were found in 79.7%, 57.8%, 23.4%, and 12.5% of the patients respectively. Before the second chemotherapy course, all the tumor marker levels except LDH decreased significantly in comparison with the pretreatment concentrations. However, only ProGRP levels showed a progressive drop during consecutive courses of therapy, while NSE and CYFRA 21-1 fluctuated within reference ranges. When the study group was divided with respect to the effect of treatment evaluated six months from its termination, significant differences in ProGRP levels were found between both subgroups throughout all therapy and follow-up, except for the fifth course of chemotherapy. Differences in NSE levels were only significant for the first two courses and follow-up. Univariate analysis showed significant relationships between disease-free survival and the initial levels of NSE and CYFRA 21-1 as well as between overall survival and prophylactic cranial irradiation (PCI) and the initial ProGRP, NSE and CYFRA 21-1 levels. Changes of ProGRP level seem to be more precise than NSE as a tool for monitoring therapy in SCLC patients with limited disease, but for prediction of relapse, in addition to NSE determinations of ProGRP seem to be optimal.

Analysis of treatment results in advanced Hodgkin's disease: the case for adjuvant radiotherapy.

PURPOSE: To assess the treatment results in patients with advanced Hodgkin's disease in a single center and to evaluate the clinical and therapeutic prognostic factors, including verification of the significance of the prognostic score. METHODS AND MATERIALS: Treatment results were analyzed in 133 patients with newly diagnosed Stage IIIB and IV Hodgkin's disease. Treatment consisted of six courses of hybrid chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]/doxorubicin (adriamycin), bleomycin, and vincristine [ABV]) followed by irradiation (RT) in patients with an indication for RT (84 patients). Chemotherapy was then continued for another two cycles. The indications for consolidation RT included bulky disease and/or partial response after six cycles of chemotherapy. In 31 patients, extended-field RT was performed, and in 53, limited fields were irradiated. The median radiation dose was 39 Gy. RESULTS: The median follow-up was 78 months. Complete remission after whole treatment was achieved in 88.7% of patients. The actuarial overall survival rate was 78% and 71%, and relapse-free survival rate was 73% and 65% at 5 and 10 years, respectively. The independent adverse prognostic factors in multivariate analysis appeared to be older age, low serum albumin, low serum gammaglobulin, lower number of chemotherapy cycles, and no RT. The value of the prognostic score was confirmed; the higher the prognostic score, the worse the survival. CONCLUSION: In patients with advanced Hodgkin's disease, consolidation RT improved survival. The best results were achieved with the use of large-volume RT.