Clinical results and toxicity for short-course preoperative radiotherapy and total mesorectal excision in rectal cancer patients.

Short-course preoperative radiotherapy (SCPRT) is an alternative method to chemoirradiation for patients with Stage II and III rectal cancer when no downsizing is needed, but there is still widespread reluctance to use this method because of fear of side effects from high-fraction doses. This paper reports on a single institution patient cohort of operated rectal cancer patients after SCPRT, evaluated for chronic adverse effects, local control, progression-free survival and overall survival. Altogether, 257 patients were treated with SCPRT and surgery including total mesorectal excision (92% total mesorectal excision = TME) between 2002 and 2009. Local control and survival were analyzed. Chronic adverse effects for 154 patients without local relapse were evaluated according to the NCI-CTCAE version 4.0 classification, with a median follow-up of 48 months. We found a 5-year disease-free survival (DFS) and overall survival (OS) of 71%. The 5-year estimated local control (LC) rate was 94%. A positive resection margin was found in 4% of the patients and was significantly correlated with decreased DFS, OS and LC. Chronic adverse effects were reported by 58% of the patients, of which 10% were Grade 3 toxicities. The most frequent Grade 2 toxicity was stool incontinence (13%). Sexual dysfunction was found in 36% of the patients (31% Grade 1 or 2, and only 5% Grade 3). SCPRT combined with TME produced excellent LC rates together with a low rate of high-grade chronic adverse effects.

The role of perfusion effects in monitoring of chemoradiotherapy of rectal carcinoma using diffusion-weighted imaging.

PURPOSE: The aim of this study was to characterize and understand the therapy-induced changes in diffusion parameters in rectal carcinoma under chemoradiotherapy (CRT). The current literature shows conflicting results in this regard. We applied the intravoxel incoherent motion model, which allows for the differentiation between diffusion (D) and perfusion (f) effects, to further elucidate potential underlying causes for these divergent reports. MATERIALS AND METHODS: Eighteen patients with primary rectal carcinoma undergoing preoperative CRT were examined before, during, and after neoadjuvant CRT using diffusion-weighted imaging. Using the intravoxel incoherent motion approach, f and D were extracted and compared with postoperative tumor downstaging and volume. RESULTS: Initial diffusion-derived parameters were within a narrow range (D1 = 0.94 ± 0.12 × 10(-3) mm(2)/s). At follow-up, D rose significantly (D2 = 1.18 ± 0.13 × 10(-3) mm(2)/s; P < 0.0001) and continued to increase significantly after CRT (D3 = 1.24 ± 0.14 × 10(-3) mm(2)/s; P < 0.0001). The perfusion fraction f did not change significantly (f1 = 9.4 ± 2.0%, f2 = 9.4 ± 1.7%, f3 = 9.5 ± 2.7%). Mean volume (V) decreased significantly (V1 = 16,992 ± 13,083 mm(3); V2 = 12,793 ± 8317 mm(3), V3 = 9718 ± 6154 mm(3)). T-downstaging (10:18 patients) showed no significant correlation with diffusion-derived parameters. CONCLUSIONS: Conflicting results in the literature considering apparent diffusion coefficient (ADC) changes in rectal carcinoma under CRT for patients showing T-downstaging are unlikely to be due to perfusion effects. Our data support the view that under effective therapy, an increase in D/ADC can be observed.

Intensity modulated radiotherapy (IMRT) combined with concurrent but not adjuvant chemotherapy in primary nasopharyngeal cancer - a retrospective single center analysis.

BACKGROUND: We report our experience in 49 consecutive patients with nasopharyngeal carcinoma who were treated by Intensity-modulated radiation therapy (IMRT) combined with simultaneous but not adjuvant chemotherapy (CHT). METHODS: The medical records of 49 patients with histologically proven primary nasopharygeal carcinoma treated with IMRT and concurrent platin-based CHT (predominantly cisplatin weekly) were retrospectively reviewed. The majority of patients showed advanced clinical stages (stage III/IV:72%) with undifferentiated histology (82%). IMRT was performed in step-and-shoot technique using an integrated boost concept in 84%. In this concept, the boost volume covered the primary tumor and involved nodes with doses of 66-70.4 Gy (single dose 2.2 Gy). Uninvolved regional nodal areas were covered with doses of 54-59.4 Gy (median single dose 1.8 Gy). At least one parotid gland was spared. None of the patients received adjuvant CHT. RESULTS: The median follow-up for the entire cohort was 48 months. Radiation therapy was completed without interruption in all patients and 76% of the patients received at least 80% of the scheduled CHT. Four local recurrences have been observed, transferring into 1-, 3-, and 5-year Local Control (LC) rates of 98%, 90% and 90%. One patient developed an isolated regional nodal recurrence, resulting in 1-, 3-, and 5-year Regional Control (RC) rates of 98%. All locoregional failures were located inside the radiation fields. Distant metastases were found in six patients, transferring into 1-, 3, and 5-year Distant Control (DC) rates of 92%, 86% and 86%. Progression free survival (PFS) rates after 1, 3 and 5 years were 86%, 70% and 69% and 1-, 3- and 5-year Overall Survival (OS) rates were 96%, 82% and 79%. Acute toxicity ≥ grade III mainly consisted of dysphagia (32%), leukopenia (24%), stomatitis (16%), infection (8%) and nausea (8%). Severe late toxicity (grade III) was documented in 18% of the patients, mainly as xerostomia (10%). CONCLUSION: Concurrent chemoradiation without the addition of adjuvant chemotherapy cycles using IMRT with an integrated boost concept yielded good disease control and overall survival in patients suffering from primary nasopharyngeal cancer with acceptable acute side effects and limited rates of late toxicity.

Local setup errors in image-guided radiotherapy for head and neck cancer patients immobilized with a custom-made device.

PURPOSE: To evaluate the local positioning uncertainties during fractionated radiotherapy of head-and-neck cancer patients immobilized using a custom-made fixation device and discuss the effect of possible patient correction strategies for these uncertainties. METHODS AND MATERIALS: A total of 45 head-and-neck patients underwent regular control computed tomography scanning using an in-room computed tomography scanner. The local and global positioning variations of all patients were evaluated by applying a rigid registration algorithm. One bounding box around the complete target volume and nine local registration boxes containing relevant anatomic structures were introduced. The resulting uncertainties for a stereotactic setup and the deformations referenced to one anatomic local registration box were determined. Local deformations of the patients immobilized using our custom-made device were compared with previously published results. Several patient positioning correction strategies were simulated, and the residual local uncertainties were calculated. RESULTS: The patient anatomy in the stereotactic setup showed local systematic positioning deviations of 1-4 mm. The deformations referenced to a particular anatomic local registration box were similar to the reported deformations assessed from patients immobilized with commercially available Aquaplast masks. A global correction, including the rotational error compensation, decreased the remaining local translational errors. Depending on the chosen patient positioning strategy, the remaining local uncertainties varied considerably. CONCLUSIONS: Local deformations in head-and-neck patients occur even if an elaborate, custom-made patient fixation method is used. A rotational error correction decreased the required margins considerably. None of the considered correction strategies achieved perfect alignment. Therefore, weighting of anatomic subregions to obtain the optimal correction vector should be investigated in the future.

Intraoperative electron radiotherapy for the management of aggressive fibromatosis.

PURPOSE: We analyzed our experience with intraoperative electron radiotherapy (IOERT) followed by moderate doses of external beam radiotherapy (EBRT) after organ-sparing surgery in patients with primary or recurrent aggressive fibromatosis. METHODS AND MATERIALS: Indication for IOERT and postoperative EBRT as an individual treatment approach to avoid mutilating surgical procedures was seen when complete surgical removal seemed to be unlikely or impossible. A total of 31 lesions in 30 patients were treated by surgery and IOERT with a median dose of 12 Gy. Median age was 31 years (range, 13-59 years). Resection status was close margin in six lesions, microscopically positive in 13, and macroscopically positive in 12. Median tumor size was 9 cm. In all, 25 patients received additional EBRT, with a median dose of 45 Gy (range, 36-54 Gy). RESULTS: After a median follow-up of 32 months (range, 3-139 months), no disease-related deaths occurred. A total of five local recurrences were seen, resulting in actuarial 3-year local control rates of 82% overall and 91% inside the IOERT areas. Trends to improved local control were seen for older age (>31 years) and negative margins, but none of these factors reached significance. Perioperative complications were found in six patients, in particular as wound healing disturbances in five patients and venous thrombosis in one patient. Late toxicity was seen in five patients. CONCLUSION: Introduction of IOERT into a multimodal treatment approach in patients with aggressive fibromatosis is feasible with low toxicity and yielded good local control rates even in patients with microscopical or gross residual disease.

Quantitative assessment of image-guided radiotherapy for paraspinal tumors.

PURPOSE: To evaluate stereotactic positioning uncertainties of patients with paraspinal tumors treated with fractionated intensity-modulated radiotherapy; and to determine whether target-point correction via rigid registration is sufficient for daily patient positioning. PATIENTS AND METHODS: Forty-five patients with tumors at the cervical, thoracic, and lumbar spine received regular control computed-tomography (CT) scans using an in-room CT scanner. All patients were immobilized with the combination of Scotch cast torso and head masks. The positioning was evaluated regarding translational and rotational errors by applying a rigid registration algorithm based on mutual information. The registration box was fitted to the target volume for optimal registration in the high-dose area. To evaluate the suitability of the rigid registration result for correcting the target volume position we subsequently registered three small subsections of the upper, middle, and lower target volume. The resulting residual deviations reflect the extent of the elastic deformations, which cannot be covered by the rigid-body registration procedure. RESULTS: A total of 321 control CT scans were evaluated. The rotational errors were negligible. Translational errors were smallest for cervical tumors (-0.1 +/- 1.1, 0.3 +/- 0.8, and 0.1 +/- 0.9 mm along left-right, anterior-posterior, and superior-inferior axes), followed by thoracic (0.8 +/- 1.1, 0.3 +/- 0.8, and 1.1 +/- 1.3 mm) and lumbar tumors (-0.7 +/- 1.3, 0.0 +/- 0.9, and 0.5 +/- 1.6 mm). The residual deviations of the three subsections were <1 mm. CONCLUSIONS: The applied stereotactic patient setup resulted in small rotational errors. However, considerable translational positioning errors may occur; thus, on the basis of these data daily control CT scans are recommended. Rigid transformation is adequate for correcting the target volume position.

Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC).

BACKGROUND: The clinical results after stereotactic single-dose radiotherapy of nonsmall-cell lung cancer (NSCLC) stages I and II were evaluated. METHODS: Forty-two patients with biopsy-proven NSCLC received stereotactic radiotherapy. Patients were treated in a stereotactic body frame and breathing motion was reduced by abdominal compression. The single doses used ranged between 19 and 30 Gy/isocenter. RESULTS: After a median follow-up period of 15 months (range, 1.5-72 months) the actuarial overall survival rates and disease-free survival rates were 74.5%, 65.4%, 37.4%, and 70.2%, 49.1%, 49.1% at 12, 24, and 36 months after therapy, respectively. The actuarial local tumor control rates were 89.5%, 67.9%, and 67.9% at 12, 24, and 36 months after therapy, respectively. A significant difference (P = .032) in local tumor control was found for patients receiving 26-30 Gy (n = 32) compared with doses of less than 26 Gy (n = 10). The effect of the tumor volume on local tumor control was also evaluated. Although the difference was not statistically significant (P = .078), the subgroup of tumors with a tumor volume of less than 12 cm(3) (n = 10) experienced no tumor recurrence. Thirteen (31%) patients developed metastases during follow-up, whereas isolated regional lymph node recurrence was only encountered in 2 patients. No clinically significant treatment-associated side effects were documented. CONCLUSIONS: Stereotactic single-dose radiotherapy is a safe and effective treatment option for patients with early stage NSCLC not suitable for surgery. Especially for small tumor volumes it seems to be equally effective as hypofractionated radiotherapy, while minimizing the overall treatment time.

3-D-conformal radiation therapy for pediatric giant cell tumors of the skull base.

BACKGROUND: Giant cell tumors (GCT) of the base of skull are rare neoplasms. This report reviews the treatment of four pediatric patients presenting with aggressive giant cell tumor, using fractionated and combined, conformal proton and photon radiation therapy at Massachusetts General Hospital and Harvard Cyclotron Laboratory. PATIENTS AND METHODS: Three female patients and one adolescent male, ages 10-15 years, had undergone prior, extensive surgical resection(s) and were treated for either primary (two patients) or recurrent (two patients) disease. Gross residual tumor was evident in three patients and microscopic disease suspected in one patient. Combined proton and photon radiation therapy was based on three-dimensional (3-D) planning, consisting of fractionated treatment, one fraction per day at 1.8 CGE (cobalt-gray equivalent) to total target doses of 57.6, 57.6, 59.4, and 61.2 Gy/CGE. RESULTS: With observation times of 3.1 years, 3.3, 5.3, and 5.8 years, all four patients were alive and well and remained locally controlled without evidence of recurrent disease. Except for one patient with partial pituitary insufficiency following radiotherapy for sellar recurrent disease, thus far no late effects attributable to radiation therapy have been observed. CONCLUSIONS: 3-D-conformal radiation therapy offers a realistic chance of tumor control for aggressive giant cell tumor in the skull base, either postoperatively or at time of recurrence. Conformal treatment techniques allow the safe delivery of relatively high radiation doses in the pediatric patient without apparent increase of side effects.

Conformal proton radiation therapy for pediatric low-grade astrocytomas.

BACKGROUND: To evaluate the safety and efficacy of proton radiation therapy (PRT) for intracranial low-grade astrocytomas, the authors analyzed the first 27 pediatric patients treated at Loma Linda University Medical Center (LLUMC). PATIENTS AND METHOD: Between September 1991 and August 1997, 27 patients (13 female, 14 male) underwent fractionated proton radiation therapy for progressive or recurrent low-grade astrocytoma. Age at time of treatment ranged from 2 to 18 years (mean: 8.7 years). Tumors were located centrally (diencephalic) in 15 patients, in the cerebral and cerebellar hemispheres in seven patients, and in the brainstem in five patients. 25/27 patients (92%) were treated for progressive, unresectable, or residual disease following subtotal resection. Tissue diagnosis was available in 23/27 patients (85%). Four patients with optic pathway tumors were treated without histologic confirmation. Target doses between 50.4 and 63.0 CGE (Cobalt Gray Equivalent, mean: 55.2 CGE) were prescribed at 1.8 CGE per fraction, five treatments per week. RESULTS: At a mean follow-up period of 3.3 years (0.6-6.8 years), 6/27 patients experienced local failure (all located within the irradiated field), and 4/27 patients had died. By anatomic site these data translated into rates of local control and survival of 87% (13/15 patients) and 93% (14/15 patients) for central tumors, 71% (5/7 patients) and 86% (6/7 patients) for hemispheric tumors, and 60% (3/5 patients) and 60% (3/5 patients) for tumors located in the brainstem. Proton radiation therapy was generally well tolerated. All children with local control maintained their performance status. One child with associated neurofibromatosis, Type 1, developed Moyamoya disease. All six patients with optic pathway tumors and useful vision maintained or improved their visual status. CONCLUSIONS: This report on pediatric low-grade astrocytomas confirms proton radiation therapy as a safe and efficacious 3-D conformal treatment modality. Results are encouraging for central tumors as well as large optic pathway tumors, where dose conformity is of particular importance; yet it is difficult to achieve. Longer follow-up time is needed to fully evaluate the benefits of normal tissue sparing.