Intrafraction Prostate Motion Management for Ultra-Hypofractionated Radiotherapy of Prostate Cancer.

Purpose: Determine the time-dependent magnitude of intrafraction prostate displacement and a cutoff for the tracking decision. Methods: Nine patients with localized prostate cancer were treated with ultra-hypofractionated radiotherapy (CyberKnife) with fiducial markers. Exact tract kV/kV imaging was used with an average interval of 19−92 s. A Gaussian distribution was calculated for the x-, y-, and z-directions (σx,y,z). The variation of prostate motion (µσ) was obtained by averaging the patients' specifics, and the safety margin was calculated to be MAB = WYm + WBSs. Results: The calculated PTV safety margins were as follows: at 40 s: 0.55 mm (L/r), 0.85 mm (a/p), and 1.05 mm (s/i); at 60 s: 0.9 mm (L/r), 1.35 mm (a/p), and 1.55 mm (s/i); at 100 s: 1.5 mm (L/r), 2.3 mm (a/p), and 2.6 mm (s/i); at 150 s: 1.9 mm (L/r), 3.1 mm (a/p), and 3.6 mm (s/i); at 200 s: 2.2 mm (L/r), 3.8 mm (a/p), and 4.2 mm (s/i); and at 300 s: 2.6 mm (L/r), 5.3 mm (a/p), and 5.6 mm (s/i). A tracking cutoff of 2.5 min seemed reasonable. In order to achieve an accuracy of < 1 mm, tracking with < 50 s intervals was necessary. Conclusions: For ultra-hypofractionated radiotherapy of the prostate with treatment times > 2.5 min, intrafraction motion management is recommended.

Long-term intra-fractional motion of the prostate using hydrogel spacer during Cyberknife® treatment for prostate cancer--a case report.

BACKGROUND: There is a trend towards hypofractionated stereotactic radiotherapy (RT) in prostate cancer to apply high single doses in a few fractions. Using the Cyberknife® robotic system multiple non-coplanar fields are usually given with a treatment time of one hour or more. We planned to evaluate organ motion in this setting injecting a hydrogel spacer to protect the anterior rectal wall during treatment. METHODS: A 66 years old man with low risk prostate cancer was planned for robotic hypofractionated stereotactic RT. After implantation of fiducial markers and a hydrogel spacer a total dose of 36.25 Gy in 5 fractions was given to the planning target volume (clinical target volume + 3 mm). After each beam the corresponding data reporting on the intra-fractional movement were pre-processed, the generated log-files extracted and the data analysed according to different directions: left -right (LR); anterior - posterior (AP); inferior -superior (IS). Clinical assessments were prospectively done before RT start, one week after the end of treatment as well as 1, 6 and 12 months afterwards. Symptoms were documented using Common Toxicity and Adverse Events Criteria 4.0. RESULTS: Tolerability of marker and hydrogel implantation was excellent. A total of 284 non-coplanar fields were used per fraction. The total treatment time for all fields per fraction lasted more than 60 minutes. The detected and corrected movements over all 5 fractions were in a range of +/- 4 mm in all directions (LR: mean 0,238 - SD 0,798; AP: mean 0,450 - SD 1,690; and IS: mean 0,908 - SD 1,518). V36Gy for the rectum was 0.062 ccm. After RT, grade 1-2 intestinal toxicity and grade 1 genitourinarytoxicity occurred, but resolved completely after 10 days. On 1-, 6- and 12-months follow-up the patient was free of any symptoms with only slight decrease of erectile function (grade 1). There was a continuous PSA decline. CONCLUSIONS: Prostate movement was relatively low (+/- 4 mm) even during fraction times of more than 60 minutes. The hydrogel spacer might serve as a kind of stabilisator for the prostate, but this should be analysed in a larger cohort of patients.

Objective response to radiation therapy and long-term survival of patients with WHO grade II astrocytic gliomas with known LOH 1p/19q status.

BACKGROUND: WHO grade II gliomas are often approached by radiation therapy (RT). However, little is known about tumor response and its potential impact on long-term survival. PATIENTS AND METHODS: Patients subjected to RT were selected from the own database of WHO grade II gliomas diagnosed between 1991 and 2000. The volumetric tumor response after RT was assessed based on magnetic resonance imaging and graded according to standard criteria as complete, partial (PR, >or= 50%), or minor (MR, 25% to <50%). RESULTS: There were 24 astrocytomas and three oligoastrocytomas. 21 patients (78%) were dead at follow-up (mean survival 74 months). None of the patients had chemotherapy. Objective response occurred in 14 patients (52%, five PR and nine MR) but was not associated with overall survival. The vast majority of the tumors had no loss of heterozygosity (LOH) 1p and/or 19q (86%). CONCLUSION: Approximately 50% of patients with astrocytic WHO grade II gliomas respond to RT despite the absence of LOH for 1p/19q. The potential predictive factors for response and the impact of response on overall survival remain unclear.

Histologic characteristics and tumor spread of recurrent glottic carcinoma: analysis on whole-organ sections and comparison with tumor spread of primary glottic carcinomas.

BACKGROUND: The assessment of the precise tumor extent of recurrent glottic carcinomas is a challenge. METHODS: The histologic characteristics of 29 recurrent glottic carcinomas after radiation failures, initially classified as T1 and T2, were analyzed on whole-organ slices. The growth patterns of 21 recurrent prT3 and prT4 and 52 primary pT3 and pT4 carcinomas were compared. RESULTS: Fifteen of 29 (52%) recurrent carcinomas were under-staged by imaging studies and endoscopy. Most recurrent carcinomas presented with multicentric tumor foci, whereas most primary carcinomas with a concentric tumor growth pattern (p < .05). Undifferentiated dissociated tumor cells were observed more often in the vicinity of recurrent tumor foci than of the primary tumor mass (p < .05). CONCLUSION: Recurrent glottic carcinomas are often under-staged and present with multiple tumor foci dispersed in different regions of the larynx. If voice-preserving salvage surgery is considered as a treatment option, these facts should be kept in mind.

Radionecrosis or tumor recurrence after radiation of laryngeal and hypopharyngeal carcinomas.

OBJECTIVE: To analyze the incidence and diagnostic difficulties of radionecrosis vs tumor recurrence of laryngeal and hypopharyngeal carcinomas. STUDY DESIGN AND SETTING: Retrospective study on 341 patients treated by radiation alone or radiochemotherapy. The clinicopathologic findings, work-up, treatment, and follow-up of 20 patients with symptoms suggestive but negative for tumor recurrence on initial imaging studies and endoscopy were analyzed. RESULTS: The incidence of chondroradionecrosis in 341 irradiated patients was 5%. Ten of 20 patients initially negative for tumor recurrence were treated by total laryngectomy; in all laryngectomy specimens, chondroradionecrosis was present, in six specimens associated with tumor recurrence. Ten patients were treated by tracheotomy and tumor recurrence was detected in one patient during follow-up. CONCLUSION: Chondroradionecrosis is a relatively rare treatment complication. Typical imaging findings suggestive of radionecrosis are often missing. Tumor recurrence may be present beneath an intact mucosa and missed by endoscopy.

Outcomes and patterns of failure in solitary plasmacytoma: a multicenter Rare Cancer Network study of 258 patients.

PURPOSE: To assess the outcomes and patterns of failure in solitary plasmacytoma (SP). METHODS AND MATERIALS: The data from 258 patients with bone (n = 206) or extramedullary (n = 52) SP without evidence of multiple myeloma (MM) were collected. A histopathologic diagnosis was obtained for all patients. Most (n = 214) of the patients received radiotherapy (RT) alone; 34 received chemotherapy and RT, and 8 surgery alone. The median radiation dose was 40 Gy. The median follow-up was 56 months (range 7-245). RESULTS: The median time to MM development was 21 months (range 2-135), with a 5-year probability of 45%. The 5-year overall survival, disease-free survival, and local control rate was 74%, 50%, and 86%, respectively. On multivariate analyses, the favorable factors were younger age and tumor size <4 cm for survival; younger age, extramedullary localization, and RT for disease-free survival; and small tumor and RT for local control. Bone localization was the only predictor of MM development. No dose-response relationship was found for doses >30 Gy, even for larger tumors. CONCLUSION: Progression to MM remains the main problem. Patients with extramedullary SP had the best outcomes, especially when treated with moderate-dose RT. Chemotherapy and/or novel therapies should be investigated for bone or bulky extramedullary SP.

Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.

BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety. METHODS: Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESULTS: A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients. CONCLUSIONS: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.

Acute radiation colitis in patients treated with short-term preoperative radiotherapy for rectal cancer.

The histopathologic features of acute radiation-induced colitis in humans have been described in occasional, >20-year-old studies, but they have not been analyzed in detail. We characterize such findings in 34 patients with rectal cancer who underwent surgery a few days after preoperative irradiation with 25 Gy given over 5-7 days, and we compare the results to the histopathologic features detected in 18 patients treated by a conventional preoperative irradiation protocol consisting of 45 Gy during 5 weeks followed by surgery after a time interval of at least 3 weeks. Short-term preoperative irradiation therapy generally induced severe mucosal inflammation characterized by increased cellularity of the lamina propria, prominent eosinophilic infiltrates, crypt disarray, surface and crypt epithelial damage, nuclear abnormalities, and presence of apoptotic bodies in the crypt epithelium. These histopathologic features were absent or detected only occasionally in the patient group treated according to the long-term preoperative irradiation protocol. Despite acute severe inflammation, none of the patients treated by short-term irradiation developed perioperative complications. These observations indicate that acute radiation colitis may remain clinically silent and resolve spontaneously within a few weeks after irradiation. Given the widening acceptance of short-term preoperative irradiation protocols for rectal cancer, pathologists should be aware of the rather characteristic histologic findings of acute radiation colitis and avoid unnecessary concern of clinicians. The differential diagnosis includes infectious colitis, collagenous and ischemic colitis, nonsteroidal anti-inflammatory drug-associated colitis, and chronic idiopathic inflammatory bowel disease.