N.S. Ramsinghani

Brachytherapy for primary and recurrent nasopharyngeal carcinoma: 20 years' experience at Long Beach Memorial.

PURPOSE We evaluated treatment outcomes of patients with mostly locally advanced primary and recurrent cancer of the nasopharynx managed with interstitial and intraluminal brachytherapy. METHODS AND MATERIALS This is a retrospective analysis of 56 patients with cancer arising from the nasopharynx treated with interstitial and intracavitary afterloading brachytherapy from 1978 to 1997. Patients were divided into three treatment groups: 15 patients with primary cancer (Group 1), 34 patients with recurrent or persistent disease (Group 2), and 7 patients with cancer in the nasopharynx who had history of previous definitive radiation therapy to the nasopharynx for head and neck cancer (Group 3). Fifty-three percent of patients in Group 1 had 1992 AJCC Stage IV disease, and 49% of patients in Groups 2 and 3 had extensive disease (defined as T3, T4, or parapharyngeal extension). Group 1 received megavoltage radiation to 50-60 Gy followed by a boost to the primary site and neck (in cases of persistent neck disease) with a combination of interstitial and intracavitary brachytherapy (mean dose 33-37 Gy). Five patients received chemotherapy, and 6 patients received hyperthermia. Groups 2 and 3 patients were treated with brachytherapy implants (mean dose 50-58 Gy) without external beam radiation. Twenty-five patients received chemotherapy either before or during radiation, and 21 patients received hyperthermia. RESULTS The overall survival at 2, 5, and 10 years for patients in Group 1 was 79%, 61%, and 61%, respectively, and for patients in Groups 2 and 3 combined was 48%, 30%, and 20%, respectively. Cause-specific survival at 2, 5, and 10 years was 87%, 74%, and 74%, respectively, for patients in Group 1; and 82%, 60%, and 60%, respectively, for patients in Groups 2 and 3. Local control at 2, 5, and 10 years was 93%, 93%, and 77%, respectively, for patients in Group 1; and 81%, 59%, and 49%, respectively, for patients in Groups 2 and 3. Control in the neck at 2, 5, and 10 years was achieved in 93%, 93%, and 93% of patients, respectively, in Group 1; and 88%, 81%, and 81%, respectively, for patients in Groups 2 and 3. Disease-free survival was 87%, 74%, and 62%, respectively, for patients in Group 1, and 56%, 41%, and 34%, respectively, for patients in Groups 2 and 3. There were 4 peri-operative deaths. One death (2%) was attributable to the development of late complications. Forty-five percent of patients experienced some form of late complications. CONCLUSION Interstitial afterloading brachytherapy can provide effective treatment for nasopharyngeal cancers, especially for locally persistent/recurrent and locally extensive lesions.

Intensity-modulated radiotherapy for previously irradiated, recurrent head-and-neck cancer

The purpose of this work is to evaluate our initial experience in treating previously irradiated, recurrent head-and-neck cancers using intensity-modulated radiotherapy (IMRT). Between July 1997 and September 1999, 12 patients with previously irradiated, locally recurrent head-and-neck cancers were treated with IMRT. These included cancers of the nasopharynx, oropharynx, hypopharynx, larynx, paranasal sinus, skin of the head-and-neck region, and malignant melanoma. Five of these 12 patients had received radiation as the primary treatment, with doses ranging from 66.0 to 126.0 Gy, and the remaining 7 patients had undergone definitive surgeries followed by an adjuvant course of radiation treatment, with doses ranging between 36.0 and 64.8 Gy. Recurrence after the initial course of radiation occurred in periods ranging from 4 to 35 months, with 11 of 12 cases recurring fully in the fields of previous irradiation. Recurrent tumors were treated with IMRT to total doses between 30 to 70 Gy (> 50 Gy in 10 cases) prescribed at the 75% to 92% isodose lines with daily fractions of 1.8 to 2 Gy. The results revealed that acute toxicities were acceptable except in 1 patient who died of aspiration pneumonia during the course of retreatment. There were 4 complete responders, 2 partial responders, and 2 patients with stable disease in the IMRT-treated volumes. Three patients received IMRT as adjuvant treatment following salvage surgery. At 4 to 16 months of follow-up, 7 patients were still alive, with 5 revealing no evidence of disease. In conclusion, this pilot study demonstrates that IMRT offers a viable mode of re-irradiation for recurrent head-and-neck cancers in previously irradiated sites. Longer follow-up time and a larger number of patients are needed to better define the therapeutic advantage of IMRT in recurrent, previously irradiated head-and-neck cancers.

The use of RapidArc volumetric-modulated arc therapy to deliver stereotactic radiosurgery and stereotactic body radiotherapy to intracranial and extracranial targets

Twenty-three targets in 16 patients treated with stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT) were analyzed in terms of dosimetric homogeneity, target conformity, organ-at-risk (OAR) sparing, monitor unit (MU) usage, and beam-on time per fraction using RapidArc volumetric-modulated arc therapy (VMAT) vs. multifield sliding-window intensity-modulated radiation therapy (IMRT). Patients underwent computed tomography simulation with site-specific immobilization. Magnetic resonance imaging fusion and optical tracking were incorporated as clinically indicated. Treatment planning was performed using Eclipse v8.6 to generate sliding-window IMRT and 1-arc and 2-arc RapidArc plans. Dosimetric parameters used for target analysis were RTOG conformity index (CI(RTOG)), homogeneity index (HI(RTOG)), inverse Paddick Conformity Index (PCI), D(mean) and D5-D95. OAR sparing was analyzed in terms of D(max) and D(mean). Treatment delivery was evaluated based on measured beam-on times delivered on a Varian Trilogy linear accelerator and recorded MU values. Dosimetric conformity, homogeneity, and OAR sparing were comparable between IMRT, 1-arc RapidArc and 2-arc RapidArc plans. Mean beam-on times ± SD for IMRT and 1-arc and 2-arc treatments were 10.5 ± 7.3, 2.6 ± 1.6, and 3.0 ± 1.1 minutes, respectively. Mean MUs were 3041, 1774, and 1676 for IMRT, 1-, and 2-arc plans, respectively. Although dosimetric conformity, homogeneity, and OAR sparing were similar between these techniques, SRS and SBRT fractions treated with RapidArc were delivered with substantially less beam-on time and fewer MUs than IMRT. The rapid delivery of SRS and SBRT with RapidArc improved workflow on the linac with these otherwise time-consuming treatments and limited the potential for intrafraction organ and patient motion, which can cause significant dosimetric errors. These clinically important advantages make image-guided RapidArc useful in the delivery of SRS and SBRT to intracranial and extracranial targets.

Outcomes of High-Dose-Rate Interstitial Brachytherapy in the Treatment of Locally Advanced Cervical Cancer: Long-term Results

PURPOSE The purpose of this study was to determine locoregional control (LRC), disease-free survival (DFS), and toxicity of high-dose-rate interstitial brachytherapy (HDR-ISBT) in the treatment of locally advanced cervical cancer. METHODS AND MATERIALS Between March 1996 and May 2009, 116 patients with cervical cancer were treated. Of these, 106 (91%) patients had advanced disease (International Federation of Gynecology and Obstetrics stage IIB-IVA). Ten patients had stage IB, 48 had stage II, 51 had stage III, and 7 had stage IVA disease. All patients were treated with a combination of external beam radiation therapy (EBRT) to the pelvis (5040 cGy) and 2 applications of HDR-ISBT to a dose of 3600 cGy to the implanted volume. Sixty-one percent of patients also received interstitial hyperthermia, and 94 (81%) patients received chemotherapy. RESULTS Clinical LRC was achieved in 99 (85.3%) patients. Three-year DFS rates were 59%, 67%, 71%, and 57% for patients with stage IB, II, III, and IVA disease, respectively. The 5-year DFS and overall survival rates for the entire group were 60% and 44%, respectively. Acute and late toxicities were within acceptable limits. CONCLUSIONS Locally advanced cervical cancer patients for whom intracavitary BT is unsuitable can achieve excellent LRC and OS with a combination of EBRT and HDR-ISBT.

Intensity-modulated radiation therapy for the spine at the University of California, Irvine

Radiation treatment of malignant diseases of the spine poses unique challenges to the radiation oncology treatment team. Intensity-modulated radiation therapy (IMRT) offers the capability of delivering high doses to targets near the spine while respecting spinal cord tolerance. At the University of California, Irvine, 8 patients received a total of 10 courses to the spine for a variety of primary and metastatic malignant conditions. This paper discusses anatomical considerations, spinal cord radiation myelopathy, and treatment planning issues as it relates to the treatment of spinal cord lesions. Between October 1997 and August 2001, a total of 8 patients received 10 courses of IMRT for primary or metastatic disease of the spine. Cancers treated included metastatic lung, renal, adrenocortical cancers, and primary sarcomas and giant cell tumor. Five cases had 6 courses given for re-irradiation of symptomatic disease and 3 cases had 4 courses of IMRT as primary management of their spinal lesions. Although 3 courses were given postoperatively, these were for grossly residual disease. For the re-irradiation patients, the mean follow-up interval was 4 months. The local control was estimated at 14%. Of the patients treated with primary intent, the mean follow-up was 9 months and the local control rate 75%. No patients developed spinal cord complications.

A randomized, controlled, double-blind study of light emitting diode photomodulation for the prevention of radiation dermatitis in patients with breast cancer

BACKGROUND AND OBJECTIVES Radiation dermatitis occurs in a majority of patients with breast cancer who receive radiation therapy (RT), causes significant pain, and may necessitate treatment delay. Light emitting diode (LED) photomodulation has been reported to minimize radiation dermatitis. This study sought to further evaluate the efficacy of LED photomodulation in lessening radiation dermatitis. MATERIALS & METHODS After surgery, patients with breast cancer received LED photomodulation or sham treatments in conjunction with three‐dimensional conformal RT. Reactions were evaluated using standardized photographs graded according to National Cancer Institute criteria. RESULTS In the LED treatment group (n=18), no patients had grade 0 reactions, six (33.3%) had grade 1 reactions, 12 (66.7%) had grade 2 reactions, and none had a grade 3 reaction. In the sham treatment group (n=15), one (6.6%) patient had a grade 0 reaction, four (26.7%) had grade 1 reactions, 9 (60.0%) had grade 2 reactions, and one (6.7%) had a grade 3 reaction. Two (11.1%) patients in the LED treatment group and one (6.7%) in the control group had to interrupt treatment. Differences between groups were not statistically significant. CONCLUSION LED photomodulation did not reduce the incidence of radiation‐induced skin reactions or interruptions in therapy. &NA; Funding was provided for this study through the Cutting Edge Research Grant, sponsored by the American Society for Dermatologic Surgery. The GentleWaves LED Select units were loaned for this study by Light BioScience

The University of California, Irvine experience with tomotherapy using the Peacock system ☆

Our institutional experience using the Peacock system for intensity-modulated radiation therapy (IMRT) is summarized. Over 100 patients were treated using this system, which is fitted to a Clinac 600C linac. Both cranial and extracranial lesions have been treated using this modality. Immobilization is achieved either with the Talon system for cranial sites or an Aquaplast cast. Target volumes up to 500 cm3 have been treated. Multiple lesions (up to 3) were treated in one setup. The range of dose/fractionation schemes used was 15 Gy/1 fx (radiosurgical treatment) - 80 Gy/40 fx. Dose validation studies were carried out using film and ion chamber dosimetry in a specially designed phantom. Optimal dose distributions were attainable using inverse treatment planning for IMRT delivery. These were found to encompass the target volumes accurately using dose validation phantom studies. Immobilization methods used were accurate to within 1 mm, as evidenced by daily portal films. IMRT using the Peacock system offers the advantage of delivery of conformal therapy to high doses safely and accurately. This provides the opportunity for dose escalation studies, retreatment of previously treated tumors, as well as treating multiple targets in one setup. The system may be fitted to a conventional linac without major modifications.

Bone mineral density loss in thoracic and lumbar vertebrae following radiation for abdominal cancers.

PURPOSE To investigate the relationship between abdominal chemoradiation (CRT) for locally advanced cancers and bone mineral density (BMD) reduction in the vertebral spine. MATERIALS AND METHODS Data from 272 patients who underwent abdominal radiation therapy from January 1997 to May 2015 were retrospectively reviewed. Forty-two patients received computed tomography (CT) scans of the abdomen prior to initiation and at least twice after radiation therapy. Bone attenuation (in Hounsfield unit) (HU) measurements were collected for each vertebral level from T7 to L5 using sagittal CT images. Radiation point dose was obtained at each mid-vertebral body from the radiation treatment plan. Percent change in bone attenuation (Δ%HU) between baseline and post-radiation therapy were computed for each vertebral body. The Δ%HU was compared against radiation dose using Pearsons linear correlation. RESULTS Abdominal radiotherapy caused significant reduction in vertebral BMD as measured by HU. Patients who received only chemotherapy did not show changes in their BMD in this study. The Δ%HU was significantly correlated with the radiation point dose to the vertebral body (R=-0.472, P<0.001) within 4-8 months following RT. The same relationship persisted in subsequent follow up scans 9 months following RT (R=-0.578, P<0.001). Based on the result of linear regression, 5 Gy, 15 Gy, 25 Gy, 35 Gy, and 45 Gy caused 21.7%, 31.1%, 40.5%, 49.9%, and 59.3% decrease in HU following RT, respectively. Our generalized linear model showed that pre-RT HU had a positive effect (β=0.830) on determining post-RT HU, while number of months post RT (β=-0.213) and radiation point dose (β=-1.475) had a negative effect. A comparison of the predicted versus actual HU showed significant correlation (R=0.883, P<0.001) with the slope of the best linear fit=0.81. Our models predicted HU were within ±20 HU of the actual value in 53% of cases, 70% of the predictions were within ±30 HU, 81% were within ±40 HU, and 90% were within ±50 HU of the actual post-RT HU. Four of 42 patients were found to have vertebral body compression fractures in the field of radiation. CONCLUSIONS Patients who receive abdominal chemoradiation develop significant BMD loss in the thoracic and lumbar vertebrae. Treatment-related BMD loss may contribute to the development of vertebral compression fractures. A predictive model for post-CRT BMD changes may inform bone protective strategies in patients planned for abdominal CRT.

Phase I/II trial of low dose cyclosporin A with EP for advanced non-small cell lung cancer1

Abstract We and others have shown that cyclosporin A (CsA) reverses resistance to etoposide (E) and cis -platinum (P) in vitro and in vivo. To assess the clinical relevance of combined therapy, we studied CsA with EP in patients with advanced non-small cell lung cancer in a phase I/II clinical trial in a University setting. Patients were treated between July 1989 and June 1994 and included 10 females and 34 males with a median age of 61 years and a mean Karnofsky performance status of 80. CsA was given at escalating doses of 1–6 mg/kg per day on days 1–4 of each 21 day cycle with cis -platinum 25 mg/m 2 per day and etoposide 100 mg/m 2 per days on days 1–3. Response was assessed after each 2 cycles by measuring index lesions. A total of 44 patients received 133 cycles, 22.7% of patients had a partial response and 36.4% had stable disease with 8% 2-year survival. Patients receiving 1–2 mg/kg CsA had a PR rate of 37.5 and 50% SD compared to 19.4 and 33.3% for doses of 3 mg/kg or more. Although no conclusions should be drawn from this small study, the Kaplan-Meier survival curves were statistically significantly different for these two groups by the log-rank test ( P =0.047). The 2-year survival of the former group was 25% compared to 4% for the latter. In light of the potential importance of immunomodulation in cancer control, it seems prudent to balance the effects of CsA on P -glycoprotein and other drug resistance pumps against its dose-dependent immunosuppressive activity. Further studies are needed to validate the activity of low dose CsA in combination with standard chemotherapy for lung cancer.

Three-dimensional conformal radiation therapy in the liver: MRI findings along a time continuum

Abstract Recent development of 3-dimensional conformal radiation therapies provides a concentrated radiation dose to the tumor. To achieve this goal, a complex design of multiple narrow beamlets is used to shape the radiation exposure to conform to the shape of the tumor. Imaging findings after novel radiation therapy techniques differ from those of conventional radiation therapy. This article discusses changes in the liver parenchyma and tumor after conformal radiation therapy focusing on magnetic resonance imaging.