Conformal radiotherapy of prostate cancer: what is the proper technique for sparing organs-at-risk?

The aim of the current study was to evaluate the optimal coplanar technique for conformal radiotherapy of prostate cancer. Twelve inoperable patients with prostatic carcinoma were examined. Five different techniques with three-, four- and six-fields were applied for treatment of prostate and seminal vesicles with or without lymph nodes. Treatment techniques were compared by using rectum, bladder and femoral heads dose-volume histogram data. A three-field arrangement consisting of an anterior and two lateral portals resulted in the maximum rectal sparing irrespectively of the irradiated area. The maximum femoral head sparing was achieved by the technique consisting of six oblique and lateral fields. The maximum bladder protection was observed with the box technique for treatment with large pelvic fields and with the arrangement consisting of two oblique and two lateral portals for conedown irradiation. In conclusion, the presented data allow the radiotherapists to select the proper irradiation technique associated with the maximum sparing of each organ-at-risk.

Pegulated liposomal doxorubicin and cisplatin given concurrently with conventional radiotherapy: a phase I dose-escalation trial for patients with squamous cell carcinoma of head and neck and lung.

This is a phase I study of concurrent chemoradiation with pegulated liposomal doxorubicin (PLDH) and cisplatin for patients with squamous non-small cell lung cancer (NSCLC) and head and neck carcinoma (SCCHN). Nine patients with NSCLC and 9 with SCCHN were recruited in two phase I dose-escalation trials. The starting dose of PLDH was 7 mg/m2 once a week and was increased by 5 mg/m2 dose increments for every 3 patients. The standard dose of cisplatin was 20 mg/m2 once a week for 6.5-7 weeks of conventional external irradiation. The total tumor dose was 64 and 70 Gy for NSCLC and SCCHN patients respectively. The maximum tolerated dose of PLDH was 12 mg/m2 for the two cohorts of patients. Grade 3 mucositis was the dose limiting toxicity for NSCLC and SCCHN patients, at the 17 mg/m2 dose level. Three chemoradiation delays of 7 days were confirmed. The median time of follow-up was 17.9 months (range 3-36 months). Four patients died due to local-regional failure combined with distant metastases (3 patients) and pericardial effusion (1 patient). In total, there were 6/18 (33%) CRs (95% confidence interval, 11-55%), and 10/18 (55%), PRs (95% confidence interval, 32-78%). The recommended phase II PLDH dose combined to cisplatin and external irradiation is 12 mg/m2/week. The incorporation of PLDH in concomitant chemoradiation regimens for future treatment of squamous cell carcinoma of the lung and head and neck is warranted.

A phase I trial of weekly docetaxel and cisplatinum combined to concurrent hyperfractionated radiotherapy for non-small cell lung cancer and squamous cell carcinoma of head and neck.

We conducted a phase I study to evaluate the activity and tolerability of concurrent docetaxel and cisplatinum radiosensitization with hyperfractionated irradiation, in patients with advanced non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Nine patients (5 stage III(A) and 4 III(B)) with NSCLC, and 15 with SCCHN (10 stage III and 5 IV) were treated with a b.i.d. hyperfractionated (HF) radiotherapy schedule. The normalized total dose for alpha/beta ratio = 10 Gy was 69.6 Gy for NSCLC and 80.5 Gy for SCCHN patients. The standard dose of cisplatin (10 mg/m(2)) was given combined to docetaxel on a weekly basis. The docetaxel starting dose level was 10 mg/m(2)/week and was escalated by 3 mg/m(2) increments in cohorts of 8 patients (5 SCCHN and 3 NSCLC). DLT (grade 3 malaise) was observed in 4 out of 8 patients treated at the 16 mg/m(2)/week docetaxel dose level. The 13 mg/m(2)/week docetaxel dose level was defined as the MTD causing grade 3 mucositis in 4 out of 8 patients. In total 4 (17%) patients developed grade 3 neutropenia. G-CSF support was given in 1/8, 4/8, and 5/8 patients treated at the 10, 13 and 16 mg/m(2) docetaxel dose levels respectively. Fatigue was the most common adverse event (5/24: 21%) and was responsible for more than 1 week treatment delay in 4 out of 8 patients treated at the 16 mg/m(2)/week docetaxel dose level. Nine (3 NSCLC and 6 SCCHN patients: 37.5%) had treatment delay of 1 week, while 7 (3 NSCLC and 4 SCCHN: 29%) had delays of 2 weeks for combined chemoradiation sequelae. Acute hypersensitivity reactions occurred in 3 (12.5%) patients, and grade 3 mucositis in 2/8, 5/8 and 6/8 patients, treated at 10, 13 and 16 mg/m(2)/week docetaxel dose levels respectively. The overall response rate was 79% (CI = 63-96%) with 33% and 53% CRs for NSCLC and SCCHN patients respectively. There were 3 deaths among 9 NSCLC and 4 among 15 SCCHN patients. Local and/or distant disease recurrences were shown in 4 NSCLC and in 6 SCCHN patients; 5 NSCLC and 9 SCCHN patients are alive with no evidence of tumor progression at 8.5 months mean follow-up time. Radiosensitization with docetaxel and cisplatin given concurrently with HF (b.i.d.) radiotherapy on a weekly basis is a promising approach and the recommended dose for further phase II studies is 10 mg/m(2)/week for both drugs. The antitumor activity shown was significant in both types of tumors. The incorporation of docetaxel in chemoradiotherapy regimens for future treatment of squamous cell carcinoma of the lung and head and neck, merits evaluation in phase II and III trials.

Peripheral primitive neuroectodermal tumour during pregnancy.

The case of a 25-year-old primipara in the second trimester of pregnancy, suffering from a peripheral primitive neuroectodermal tumour (pPNET) diagnosed by bone biopsy, is described. External irradiation was initially performed because of Jacksonian seizures due to a lesion in the right cerebral hemisphere. Appropriate shielding was used to reduce fetal exposure during brain radiotherapy. Caesarian delivery at the 27th week of gestation was performed because of tumour progression. The neonate had no evidence of disease and survived for 1 month. However, the placenta and ovaries showed metastases from the maternal pPNET. The patient died 14 months after initial diagnosis owing to the aggressiveness of the tumour, the rapid and extensive semination (bone marrow, lung, liver, craniospinal axis involvement) and the inability to adequately treat the patient with appropriate doses of chemotherapy.