Rakesh R. Patel

Helical Tomotherapy: An Innovative Technology and Approach to Radiation Therapy

Helical tomotherapy represents both a novel radiation treatment device and an innovative means of delivering radiotherapy. The helical tomotherapy unit itself is essentially a hybrid between a linear accelerator and a helical CT scanner for the purpose of delivering intensity-modulated radiation therapy (IMRT). The imaging capacity conferred by the CT component allows targeted regions to be visualized prior to, during, and immediately after each treatment. The megavoltage CT (MVCT) images supplant the port-films used in conventional radiotherapy, providing unprecedented anatomical detail. Image-guidance through MVCT will allow the development and refinement of the concept of “adaptive radiotherapy”, the reconstruction of the actual daily delivered dose (as opposed to planned dose) accompanied by prescription and delivery adjustments when appropriate. In addition to this unique feature, helical tomotherapy appears capable of further improvements over 3-dimensional conformal radiation therapy and non-helical IMRT in the specific avoidance of critical normal structures, i.e. “conformal avoidance”, the counterpart of conformal radiation therapy. Based on radiobiological principles that exploit the physical advantages of helical tomotherapy, several dosimetric and clinical investigations are underway.

The American Brachytherapy Society consensus statement for accelerated partial breast irradiation

PURPOSE To develop clinical guidelines for the quality practice of accelerated partial breast irradiation (APBI) as part of breast-conserving therapy for women with early-stage breast cancer. METHODS AND MATERIALS Members of the American Brachytherapy Society with expertise in breast cancer and breast brachytherapy in particular devised updated guidelines for appropriate patient evaluation and selection based on an extensive literature search and clinical experience. RESULTS Increasing numbers of randomized and single and multi-institution series have been published documenting the efficacy of various APBI modalities. With more than 10-year followup, multiple series have documented excellent clinical outcomes with interstitial APBI. Patient selection for APBI should be based on a review of clinical and pathologic factors by the clinician with particular attention paid to age (≥50 years old), tumor size (≤3cm), histology (all invasive subtypes and ductal carcinoma in situ), surgical margins (negative), lymphovascular space invasion (not present), and nodal status (negative). Consistent dosimetric guidelines should be used to improve target coverage and limit potential for toxicity following treatment. CONCLUSIONS These guidelines have been created to provide clinicians with appropriate patient selection criteria to allow clinicians to use APBI in a manner that will optimize clinical outcomes and patient satisfaction. These guidelines will continue to be evaluated and revised as future publications further stratify optimal patient selection.

Dosimetric comparison of left-sided whole breast irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical tomotherapy, and topotherapy

BACKGROUND AND PURPOSE To compare left-sided whole breast conventional and intensity-modulated radiotherapy (IMRT) treatment planning techniques. MATERIALS AND METHODS Treatment plans were created for 10 consecutive patients. Three-dimensional conformal radiotherapy (3DCRT), forward-planned IMRT (for-IMRT), and inverse-planned IMRT (inv-IMRT) used two tangent beams. For-IMRT utilized up to four segments per beam. For helical tomotherapy (HT) plans, beamlet entrance and/or exit to critical structures was blocked. Topotherapy plans, which used static gantry angles with simultaneous couch translation and inverse-planned intensity modulation, used two tangent beams. Plans were normalized to 50Gy to 95% of the retracted PTV. RESULTS Target max doses were reduced with for-IMRT compared to 3DCRT, which were further reduced with HT, topotherapy, and inv-IMRT. HT resulted in lowest heart and ipsilateral lung max doses, but had higher mean doses. Inv-IMRT and topotherapy reduced ipsilateral lung mean and max doses compared to 3DCRT and for-IMRT. CONCLUSIONS All modalities evaluated provide adequate coverage of the intact breast. HT, topotherapy, and inv-IMRT can reduce high doses to the target and normal tissues, although HT results in increased low doses to large volume of normal tissue. For-IMRT improves target homogeneity compared with 3DCRT, but to a lesser degree than the inverse-planned modalities.

Rectal dose sparing with a balloon catheter and ultrasound localization in conformal radiation therapy for prostate cancer

BACKGROUND AND PURPOSE To compare the rectal wall and bladder volume in the high dose region with or without the use of a balloon catheter with both three-dimensional (3D)-conformal and intensity modulated radiation therapy (CRT, IMRT) approaches in the treatment of prostate cancer. MATERIAL AND METHODS Five patients with a wide range of prostate volumes and treated with primary external beam radiation therapy for localized prostate cancer were selected for analysis. Pinnacle treatment plans were generated utilizing a 3D conformal six-field design and an IMRT seven coplanar-field plan with a novel, three-step optimization and with ultrasound localization. Separate plans were devised with a rectal balloon deflated or air inflated with and without inclusion of the seminal vesicles (SV) in the target volume. The prescription dose was 76Gy in 38 fractions of 2Gy each. Cumulative dose-volume histograms (DVHs) were analyzed for the planning target volume (PTV), rectal wall, and bladder with an inflated (60cc air) or deflated balloon with and without SV included. The volumes of rectal wall and bladder above 60, 65, and 70Gy with each treatment approach were evaluated. RESULTS Daily balloon placement was well-tolerated with good patient positional reproducibility. Inflation of the rectal balloon in all cases resulted in a significant decrease in the absolute volume of rectal wall receiving greater than 60, 65, or 70Gy. The rectal sparing ratio (RSR), consisting of a structures high dose volume with the catheter inflated, divided by the volume with the catheter deflated, was calculated for each patient with and without seminal vesicle inclusion for 3D-CRT and IMRT. For 3D-CRT, RSRs with SV included were 0.59, 0.59, and 0.56 and with SV excluded were 0.60, 0.58, and 0.54 at doses of greater than 60, 65, and 70Gy, respectively. Similarly, for IMRT, the mean RSRs were 0.59, 0.59, and 0.63 including SV and 0.71, 0.66, and 0.67 excluding SV at these same dose levels, respectively. Averaged over all conditions, inflation of the rectal balloon resulted in a significant reduction in rectal volume receiving > or =65Gy to a mean ratio of 0.61 (P=0.01) or, in other words, a mean fractional high dose rectal sparing of 39%. There was a slight overall increase to 1.13 in the relative volume of bladder receiving at least 65Gy; however, this was not significant (P=0.6). Use of an endorectal balloon with a non-image-guided 3D-CRT plan produced about as much rectal dose sparing as a highly conformal, image-guided IMRT approach without a balloon. However, inclusion of a balloon with IMRT produced further rectal sparing still. CONCLUSION These results indicate that use of a rectal balloon with a 3D-CRT plan incorporating typical treatment margins will produce significant high dose rectal sparing that is comparable to that achieved by a highly conformal IMRT with ultrasound localization. Further sparing is achieved with the inclusion of a balloon catheter in an IMRT plan. Thus, in addition to a previously reported advantage of prostate immobilization, the use of a rectal displacement balloon during daily treatment results in high dose rectal wall sparing during both modestly and highly conformal radiotherapy. Such sparing could assist in controlling and limiting rectal toxicity during increasingly aggressive dose escalation.

Targeted Therapy for Brain Metastases: Improving the Therapeutic Ratio

Brain metastasis is the most common intracranial malignancy in adults. Improvements in modern imaging techniques are detecting previously occult brain metastases, and more effective therapies are extending the survival of patients with invasive cancer who have historically died from extracranial disease before developing brain metastasis. This combination of factors along with increased life expectancy has led to the increased diagnosis of brain metastases. Conventional treatment has been whole brain radiotherapy, which can improve symptoms, but potentially results in neurocognitive deficits. Several strategies to improve the therapeutic ratio are currently under investigation to either enhance the radiation effect, thereby preventing tumor recurrence or progression as well as reducing collateral treatment-related brain injury. In this review article, we discuss new directions in the management of brain metastases, including the role of chemical modifiers, novel systemic agents, and the management and prevention of neurocognitive deficits.

OUTCOMES AFTER ACCELERATED PARTIAL BREAST IRRADIATION IN PATIENTS WITH ASTRO CONSENSUS STATEMENT CAUTIONARY FEATURES

PURPOSE To evaluate outcomes among women with American Society for Radiation Oncology (ASTRO) consensus statement cautionary features treated with brachytherapy-based accelerated partial breast irradiation (APBI). METHODS AND MATERIALS Between March 2001 and June 2006, 322 consecutive patients were treated with high-dose-rate (HDR) APBI at the University of Wisconsin. A total of 136 patients were identified who met the ASTRO cautionary criteria. Thirty-eight (27.9%) patients possessed multiple cautionary factors. All patients received 32 to 34 Gy in 8 to 10 twice-daily fractions using multicatheter (93.4%) or Mammosite balloon (6.6%) brachytherapy. RESULTS With a median follow-up of 60 months, there were 5 ipsilateral breast tumor recurrences (IBTR), three local, and two loco-regional. The 5-year actuarial rate of IBTR was 4.8%±4.1%. The 5-year disease-free survival was 89.6%, with a cause-specific survival and overall survival of 97.6% and 95.3%, respectively. There were no IBTRs among 32 patients with ductal carcinoma in situ (DCIS) vs. 6.1% for patients with invasive carcinoma (p=0.24). Among 104 patients with Stage I or II invasive carcinoma, the IBTR rate for patients considered cautionary because of age alone was 0% vs. 12.7% in those deemed cautionary due to histopathologic factors (p=0.018). CONCLUSIONS Overall, we observed few local recurrences among patients with cautionary features. Women with DCIS and patients 50 to 59 years of age with Stage I/II disease who otherwise meet the criteria for suitability appear to be at a low risk of IBTR. Patients with tumor-related cautionary features will benefit from careful patient selection.

Helical tomotherapy as a means of delivering accelerated partial breast irradiation.

A novel treatment approach utilizing helical tomotherapy for partial breast irradiation for patients with early-stage breast cancer is described. This technique may serve as an alternative to high dose-rate (HDR) interstitial brachytherapy and standard linac-based approaches. Through helical tomotherapy, highly conformal irradiation of target volumes and avoidance of normal sensitive structures can be achieved. Unlike HDR brachytherapy, it is noninvasive. Unlike other linac-based techniques, it provides image-guided adaptive radiotherapy along with intensity modulation. A treatment planning CT scan was obtained as usual on a post-lumpectomy patient undergoing HDR interstitial breast brachytherapy. The patient underwent catheter placement for HDR treatment and was positioned prone on a specially designed position-supporting mattress during C T. The planning target volume (PTV) was defined as the lumpectomy bed plus a 20 mm margin. The prescription dose was 34 Gy (10 fx of 3.4 Gy) in both the CT based HDR and on the tomotherapy plan. Cumulative dose-volume histograms (DVHs) were generated and analyzed for the target, lung, heart, skin, pectoralis muscle, and chest wall for both HDR brachytherapy and helical tomotherapy. Dosimetric coverage of the target with helical tomotherapy was conformal and homogeneous. “Hot spots” (≥150% isodose line) were present around implanted dwell positions in brachytherapy plan whereas no isodose lines higher than 109% were present in the helical tomotherapy plan. Similar dose coverage was achieved for lung, pectoralis muscle, heart, chest wall and breast skin with the two methods. We also compared our results to that obtained using conventional linac-based three dimensional (3D) conformal accelerated partial breast irradiation. Dose homogeneity is excellent with 3D conformal irradiation, and lung, heart and chest wall dose is less than for either HDR brachytherapy or helical tomotherapy but skin and pectoral muscle doses were higher than with the other techniques. Our results suggest that helical tomotherapy can serve as an effective means of delivering accelerated partial breast irradiation and may offer superior dose homogeneity compared to HDR brachytherapy.

3D-Ultrasound Guided Radiation Therapy in the Post-Prostatectomy Setting

Daily transabdominal ultrasound-directed localization has proven valuable in correcting for setup error and organ motion in the treatment of prostate cancer with three-dimensional conformal radiation therapy (3DCRT). The present study sought to determine whether this trans-abdominal ultrasound technology could also be reliably applied in the post-operative adjuvant or salvage setting to improve the reproducibility of coverage of the intended volumes and to enhance conformal avoidance of adjacent normal structures. Sixteen consecutive patients who received external beam radiotherapy underwent daily localization using an optically guided 3D-ultrasound target localization system (SonArray™, Zmed, Inc., Ashland, MA). Six of the above patients were treated in a post-prostatectomy setting, either adjuvantly or for salvage, while the remaining 10 with intact prostates were treated definitively. Because the bladder neck generally approximates the postoperative prostatic fossa, it was used during ultrasound localization as the primary reference structure for the post-prostatectomy patients. For patients treated definitively, the prostate was the primary reference structure. Daily shifts were recorded and port films were taken weekly immediately after ultrasound-based repositioning. By comparing port films taken after ultrasound localization, which evaluates for both set-up error and internal shift, with the original digitally reconstructed radiographs (DRRs), which represents a zero clinical set-up error situation, the degree of variability in organ position was determined. The average absolute, ultrasound-based shifts from the clinical set-up position in the anterior/posterior, lateral, and cranial/caudal directions for the post-prostatectomy patients were 5 ± 4 mm SD, 3 ± 3 mm SD, and 3 ± 4 mm SD over the entire course of treatment, respectively. The average vector length shift was 8 ± 4 mm SD. For patients treated with an intact prostate, the analogous average absolute shifts in the anterior/posterior, lateral, and cranial/caudal directions were 4 ± 3 mm SD, 4 ± 3 mm SD, and 4 ± 3 mm SD over the entire course of treatment. The average vector length shift was 7 ± 4 mm SD. Vector length shifts representing interfraction internal motion were estimated by comparing post-ultrasound port films with DRRs. These were 5 ± 3 mm SD and 4 ± 4mm SD for post-prostatectomy and intact prostate patients, respectively. These ultrasound-based displacements were not statistically different in patients with an intact prostate versus patients post-prostatectomy (p > 0.1). In conclusion, daily transabdominal 3D-ultrasound localization proved to be a clinically feasible method of correcting for set-up and internal motion displacements. The bladder neck, which serves as an adequate localization reference structure for the prostatic fossa, could be readily ultrasound imaged and repositioned as necessary. Daily internal motion errors that would have occurred if only pre-treatment port films were used were similar in magnitude to those observed for the patients with intact prostates and were of sufficient magnitude to support the use of daily pre-treatment ultrasound localization in the post-prostatectomy setting.

Recommendations for permanent prostate brachytherapy with 131Cs: A consensus report from the Cesium Advisory Group

PURPOSE Published clinical information on the safety and efficacy of (131)Cs implants is limited. We provide consensus recommendations for (131)Cs prostate brachytherapy based on experience to date. METHODS AND MATERIALS The Cesium Advisory Group (CAG) consists of experienced (131)Cs users. Recommendations are based on three clinical trials, one of which has completed accrual and has been published in the peer reviewed literature, and combined CAG experience of more than 1200 (131)Cs implants. RESULTS We recommend using 1.059cGyh(-1)U(-1) as the dose rate constant for the IsoRay source. The prescription for monotherapy implants is 115Gy and when combined with 45-50Gy external beam it is 85Gy. Suggested individual source strength ranges from 1.6 to 2.2U. The release criterion for (131)Cs implants is 6mRh(-1) at 1m. (131)Cs brachytherapy should be performed differently from (125)I and (103)Pd brachytherapy: source placement is further from the urethra and rectum; the prostate V(150) should be < or =45%; sufficient margins may be obtained while limiting source placement to the capsule or close to the capsule. The increased dose rate may cause degradation of postimplant quantifiers due to edema. However, large variability in the magnitude and rate of resolution of edema make determination of the most representative postoperative imaging time impossible. The CAG recommends postimplant imaging on the day of the implant. Recommended postimplant evaluation goals include prostate D(90) greater than the prescription dose; maintaining D(u)(,30)<140% of the prescription dose and keeping V(r)(,100)<0.5cm(3). CONCLUSION It was the consensus of the CAG that optimal (131)Cs implants should be performed differently from those performed with (125)I or (103)Pd. Guidelines have been established to allow for safe and effective delivery of (131)Cs prostate brachytherapy.

Phase I Trial of Pelvic Nodal Dose Escalation with Hypofractionated IMRT for High Risk Prostate Cancer

PURPOSE Toxicity concerns have limited pelvic nodal prescriptions to doses that may be suboptimal for controlling microscopic disease. In a prospective trial, we tested whether image-guided intensity-modulated radiation therapy (IMRT) can safely deliver escalated nodal doses while treating the prostate with hypofractionated radiotherapy in 5½ weeks. METHODS AND MATERIALS Pelvic nodal and prostatic image-guided IMRT was delivered to 53 National Comprehensive Cancer Network (NCCN) high-risk patients to a nodal dose of 56 Gy in 2-Gy fractions with concomitant treatment of the prostate to 70 Gy in 28 fractions of 2.5 Gy, and 50 of 53 patients received androgen deprivation for a median duration of 12 months. RESULTS The median follow-up time was 25.4 months (range, 4.2-57.2). No early Grade 3 Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events v.3.0 genitourinary (GU) or gastrointestinal (GI) toxicities were seen. The cumulative actuarial incidence of Grade 2 early GU toxicity (primarily alpha blocker initiation) was 38%. The rate was 32% for Grade 2 early GI toxicity. None of the dose-volume descriptors correlated with GU toxicity, and only the volume of bowel receiving ≥30 Gy correlated with early GI toxicity (p = 0.029). Maximum late Grades 1, 2, and 3 GU toxicities were seen in 30%, 25%, and 2% of patients, respectively. Maximum late Grades 1 and 2 GI toxicities were seen in 30% and 8% (rectal bleeding requiring cautery) of patients, respectively. The estimated 3-year biochemical control (nadir + 2) was 81.2 ± 6.6%. No patient manifested pelvic nodal failure, whereas 2 experienced paraaortic nodal failure outside the field. The six other clinical failures were distant only. CONCLUSIONS Pelvic IMRT nodal dose escalation to 56 Gy was delivered concurrently with 70 Gy of hypofractionated prostate radiotherapy in a convenient, resource-efficient, and well-tolerated 28-fraction schedule. Pelvic nodal dose escalation may be an option in any future exploration of potential benefits of pelvic radiation therapy in high-risk prostate cancer patients.