HI-CHART: a phase I/II study on the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer.

PURPOSE: To determine the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: In a prospective, Phase I/II study, according to the risk for radiation pneumonitis, three risk groups were defined: V(20) <25%, V(20) 25-37%, and V(20) >37%. The dose was administered in three steps from 61.2 Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38 fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional conformal technique. Only the mediastinal lymph node areas that were positive on the pretreatment (18)F-deoxy-D-glucose positron emission tomography scan were included in the target volume. The primary endpoint was toxicity. RESULTS: A total of 48 Stage I-IIIB patients were included. In all risk groups, 68.40 Gy/38 fractions/25 days could be administered. Maximal toxicity according to the risk groups was as follows: V(20) <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3 reversible esophageal toxicity; V(20) 35-37% (n = 12): 1 G5 lung and 1 G3 reversible esophageal toxicity. For the whole group, local tumor recurrence occurred in 25% (95% confidence interval 14%-40%) of the patients, with 1 of 48 (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal recurrence. The median actuarial overall survival was 20 months, with a 2-year survival rate of 36%. CONCLUSIONS: High-dose continuous hyperfractionated accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a biologic equivalent of approximately 80 Gy when delivered in conventional fractionation) in patients with inoperable NSCLC and a V(20) up to 37% is feasible.

Total body irradiation, toward optimal individual delivery: dose evaluation with metal oxide field effect transistors, thermoluminescence detectors, and a treatment planning system.

PURPOSE: To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. METHODS AND MATERIALS: A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. RESULTS: The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. CONCLUSIONS: The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

Radiation-induced bullous pemphigoid: a systematic review of an unusual radiation side effect.

BACKGROUND: Percutaneous radiotherapy (RT) may cause a range of acute and late side effects of the skin within the irradiated area. In rare cases radiotherapy can cause bullous pemphigoid (BP). BP is reported to occur mainly within irradiated fields following radiation treatment. Exceptionally, BP may arise during RT. It is unclear which mechanism exactly triggers BP following megavoltage irradiation and whether there is a potential association with hormonal anticancer treatment. METHODS: A systematic literature based review was performed. Publications reporting histologically confirmed BP and a treatment with RT were retrieved based on a standardized query using electronic databases. A standardized quality assessment was applied. RESULTS: Out of 306 potentially relevant publications 21 were identified to be relevant and included in this review. An association between RT and BP was reported in 27 patients. The majority developed BP after RT and a median dose of 50 Gy. Four patients developed BP during RT after a minimal dose of 20 Gy. CONCLUSIONS: BP induced by RT was observed predominantly in patients with breast cancer. In all reported cases, there is a clear relationship with RT. Therefore, BP may be considered as RT-induced side effect. RT can induce a BP following a minimal dose of 20 Gy. New biological agents may play a role in the future treatment of BP.

Omission of elective node irradiation on basis of CT-scans in patients with limited disease small cell lung cancer: a phase II trial.

PURPOSE: To evaluate the patterns of recurrence when elective node irradiation was omitted in patients with limited disease small cell lung cancer (LD-SCLC). METHODS: A prospective phase II study was undertaken in 27 patients with LD-SCLC without detectable distant metastases on CT scan. Chest radiotherapy to a dose of 45 Gy in 30 fractions in 3 weeks (1.5 Gy BID with 6 - 8 h interval) was delivered concurrently with carboplatin and etoposide chemotherapy. Chest radiation started after a mean time of 17.7 days +/- 9.7 days (SD) (range: 0-33 days) after the beginning of chemotherapy. Only the primary tumour and the positive nodal areas on the pre-treatment CT scan were irradiated. A total of five chemotherapy cycles were administered, followed by prophylactic cranial irradiation (PCI) in patients without disease progression. Isolated nodal failure was defined as recurrence in the regional nodes outside of the clinical target volume, in the absence of in-field failure. RESULTS: After a median time of 18 months post-radiotherapy, 7 patients (26%, 95% CI 19.5-42.5%) developed a local recurrence. Three patients (crude rate 11%, 95% CI 2.4-29%), developed an isolated nodal failure, all of them in the ipsilateral supraclavicular fossa. The median actuarial overall survival was 21 months (95% CI 15.3-26.7), and the median actuarial progression free survival was 16 months (95% CI 6.5-25.5). Eight patients developed an acute, reversible grade 3 (CTC 3.0) radiation oesophagitis (30%, 95% CI 14-50%). CONCLUSIONS: Because of the small sample size, no definitive conclusions can be drawn. However, the omission of elective nodal irradiation on the basis of CT scans in patients with LD-SCLC resulted in a higher than expected rate of isolated nodal failures in the ipsilateral supraclavicular fossa. The incidence of acute, reversible oesophagitis was in the same range as reported with elective nodal fields. The safety of selective nodal irradiation in NSCLC should not be extrapolated to patients with LD-SCLC until more data are available. In the mean time, elective nodal irradiation should only be omitted in clinical trials.

Combined-modality therapy for clinical stage I or II Hodgkin's lymphoma: long-term results of the European Organisation for Research and Treatment of Cancer H7 randomized controlled trials.

PURPOSE: In early-stage Hodgkin's lymphoma (HL), subtotal nodal irradiation (STNI) and combined chemotherapy/radiotherapy produce high disease control rates but also considerable late toxicity. The aim of this study was to reduce this toxicity using a combination of low-intensity chemotherapy and involved-field radiotherapy (IF-RT) without jeopardizing disease control. PATIENTS AND METHODS: Patients with stage I or II HL were stratified into two groups, favorable and unfavorable, based on the following four prognostic factors: age, symptoms, number of involved areas, and mediastinal-thoracic ratio. The experimental therapy consisted of six cycles of epirubicin, bleomycin, vinblastine, and prednisone (EBVP) followed by IF-RT. It was randomly compared, in favorable patients, to STNI and, in unfavorable patients, to six cycles of mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV hybrid) and IF-RT. RESULTS: Median follow-up time of the 722 patients included was 9 years. In 333 favorable patients, the 10-year event-free survival rates (EFS) were 88% in the EBVP arm and 78% in the STNI arm (P = .0113), with similar 10-year overall survival (OS) rates (92% v 92%, respectively; P = .79). In 389 unfavorable patients, the 10-year EFS rate was 88% in the MOPP/ABV arm compared with 68% in the EBVP arm (P < .001), leading to 10-year OS rates of 87% and 79%, respectively (P = .0175). CONCLUSION: A treatment strategy for early-stage HL based on prognostic factors leads to high OS rates in both favorable and unfavorable patients. In favorable patients, the combination of EBVP and IF-RT can replace STNI as standard treatment. In unfavorable patients, EBVP is significantly less efficient than MOPP/ABV.

Palliative chest irradiation in sitting position in patients with bulky advanced lung cancer.

Some patients with bulky advanced lung cancer are not able to lie down because of dyspnea. We therefore designed a technique for irradiation in a sitting position by using a dedicated chair. The reproducibility of the sitting position was high and all ten patients preferred this position over lying down. In selected patients who are unable to lie down, palliative irradiation in a sitting position may be an option.

Primary spinal epidural lymphoma: patients' profile, outcome, and prognostic factors: a multicenter Rare Cancer Network study.

PURPOSE: To assess the clinical profile, treatment outcome, and prognostic factors in primary spinal epidural lymphoma (PSEL). METHODS AND MATERIALS: Between 1982 and 2002, 52 consecutive patients with PSEL were treated in nine institutions of the Rare Cancer Network. Forty-eight patients had an Ann Arbor stage IE and four had a stage IIE. Forty-eight patients underwent decompressive laminectomy, all received radiotherapy (RT) with (n = 32) or without chemotherapy (n = 20). Median RT dose was 36 Gy (range, 6-50 Gy). RESULTS: Six (11%) patients progressed locally and 22 (42%) had a systemic relapse. At last follow-up, 28 patients were alive and 24 had died. The 5-year overall survival, disease-free survival, and local control were 69%, 57%, and 88%, respectively. In univariate analyses, favorable prognostic factors were younger age and complete neurologic response. Multivariate analysis showed that combined modality treatment, RT volume, total dose more than 36 Gy, tumor resection, and complete neurologic response were favorable prognostic factors. CONCLUSIONS: Primary spinal epidural lymphoma has distinct clinical features and outcome, with a relatively good prognosis. After therapy, local control is excellent and systemic relapse occurs in less than half the cases. Combined modality treatment appears to be superior to RT alone.

Effects of radiotherapy planning with a dedicated combined PET-CT-simulator of patients with non-small cell lung cancer on dose limiting normal tissues and radiation dose-escalation: a planning study.

BACKGROUND AND PURPOSE: To investigate the effect of radiotherapy planning with a dedicated combined PET-CT simulator of patients with locally advanced non-small cell lung cancer. PATIENTS AND METHODS: Twenty-one patients underwent a pre-treatment simulation on a dedicated hybrid PET-CT-simulator. For each patient, two 3D conformal treatment plans were made: one with a CT based PTV and one with a PET-CT based PTV, both to deliver 60Gy in 30 fractions. The maximum tolerable prescribed radiation dose for CT versus PET-CT PTV was calculated based on constraints for the lung, the oesophagus, and the spinal cord, and the Tumour Control Probability (TCP) was estimated. RESULTS: For the same toxicity levels of the lung, oesophagus and spinal cord, the dose could be increased from 55.2+/-2.0Gy with CT planning to 68.9+/-3.3Gy with the use of PET-CT (P=0.002), with corresponding TCP's of 6.3+/-1.5% for CT and 24.0+/-5.6% for PET-CT planning (P=0.01). CONCLUSIONS: The use of a combined dedicated PET-CT-simulator reduced radiation exposure of the oesophagus and the lung, and thus allowed significant radiation dose escalation whilst respecting all relevant normal tissue constraints.

Selective mediastinal node irradiation based on FDG-PET scan data in patients with non-small-cell lung cancer: a prospective clinical study.

PURPOSE: To evaluate the patterns of recurrence when selective mediastinal node irradiation based on FDG-PET scan data is used in patients with non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: A prospective Phase I/II study was undertaken on 44 patients with NSCLC without detectable distant metastases on CT and FDG-PET scan, delivering either 61.2 Gy in 34 fractions over 23 days or 64.8 Gy in 36 fractions over 24 days (1.8 Gy b.i.d. with 8-h interval). Only the primary tumor and the positive mediastinal areas on the pretreatment FDG-PET scan were irradiated. Isolated nodal failure was defined as recurrence in the regional nodes outside of the clinical target volume, in the absence of in-field failure. RESULTS: The CT and FDG-PET stage distribution was as follows: Stage I: 8 patients (18%) and 13 patients (29%); Stage II: 6 patients (14%) and 10 patients (23%); Stage IIIA: 15 patients (34%) and 7 patients (16%); Stage IIIB: 15 patients (34%) and 14 patients (32%), respectively. After a median follow-up time of 16 months (95% confidence interval [CI], 11-21 months) postradiotherapy, 11 patients (25%) developed a local recurrence. Only 1 patient (crude rate, 2.3%; upper bound of 95% CI, 10.3%), with a Stage II tumor on both CT and PET, developed an isolated nodal failure. The median actuarial overall survival was 21 months (95% CI, 14-28 months), and the median actuarial progression-free survival was 18 months (95% CI, 12-24 months). CONCLUSIONS: Selective mediastinal node irradiation based on FDG-PET scan data in patients with NSCLC results in low isolated nodal failure rates. In the Phase I component of this trial, radiation dose escalation up to 64.8 Gy in 36 fractions over 24 days is feasible.