Effects of tumor motion in GRID therapy.

Clinical and biological evidence suggest that the success of GRID therapy in debulking large tumors depends on the high peak-to-valley contrast in the dose distribution. In this study, we show that the peaks and valleys can be significantly blurred out by respiration-induced tumor motion, possibly affecting the clinical outcome. Using a kernel-based Monte Carlo dose engine that incorporates phantom motion, we calculate the dose distributions for a GRID with hexagonally arranged holes. The holes have a diameter of 1.3 cm and a minimum center-to-center separation of 2.1 cm (projected at the isocenter). The phantom moves either in the u parallel direction, which is parallel to a line joining any two nearest neighbors, or in the perpendicular u perpendicular direction. The displacement-time waveform is modeled with a cosn function, with n assigned 1 for symmetric motion, or 6 to simulate a large inhale-exhale asymmetry. Dose calculations are performed on a water phantom for a 6 MV x-ray beam. Near dmax, the static valley dose is 0.12D0, where D0 is the peak static dose. For motion in the u parallel direction, the peak and valley doses vary periodically with the amplitude of motion a and the transverse dose profiles are maximally flat near a=0.8 cm and a=1.9 cm. For the cos waveform, the minimum peak dose (Dpmin) is 0.67D0 and the maximum valley dose (Dvmax) is 0.60D0. Less dose blurring is seen with the cos6 waveform, with Dpmin=0.77D0 and Dvmax=0.45D0. For motion in the u perpendicular direction, the maximum flattening of dose profiles occurs at a=1.5 cm. GRIDs with smaller hole separations produce similar blurring at proportionally smaller amplitudes. The reported clinical response data from GRID therapy seem to indicate that mobile tumors, such as those in the thorax and abdomen, respond worse to GRID treatments than stationary tumors, such as those in the head and neck. To establish a stronger correlation between clinical response and tumor motion, and possibly improve the clinical response rates, it is recommended that prospective GRID therapy trials be conducted with motion compensation strategies, such as respiratory gating.

Adjuvant pelvic irradiation for cervical cancer in the setting of a transplanted pelvic kidney.

Postoperative radiation therapy is often needed following resection for gynecological cancers. A pelvic kidney, whether ectopic or transplanted, is considered an absolute contraindication for radiation if the organ is left in place. A 45-year-old, immunosuppressed patient with FIGO IB1 cervical adenocarcinoma was treated with intensity-modulated radiation therapy (IMRT) to 45 Gy to the modified whole pelvis with a boost to 59.4 Gy to high-risk areas despite having a transplanted kidney in the right iliac fossa. The irradiation prevented further local failure in the pelvis at 36-month follow-up with no decrement in renal function. Radiation to the modified pelvis using IMRT while avoiding the renal allograft is technically feasible and should be offered to more high-risk patients.

Decrease of the lumpectomy cavity volume after whole-breast irradiation affects small field boost planning.

To determine whether small field boost (SFB) replanning is necessary when the lumpectomy cavity (LPC) decreases during whole-breast irradiation (WBI) and what parameters might predict a change in the SFB plan. Forty patients had computed tomography (CT) simulation (CT1) within 60 days of surgery and were resimulated (CT2) after 37.8-41.4 Gy for SFB planning. A 3-field photon plan and a single en face electron plan were created on both CTs and compared. In the 26 patients who had a ≥5 cm(3) and a ≥25% decrease in lumpectomy cavity volume (LCV) between CT scans, the SFB plan using photons was different in terms of normal breast tissue volume irradiated (BTV) (p < 0.001), and field dimensions (p < 0.001). In 20/35 patients, the energy or field size changed for electron plans on CT2, but no tested characteristics predicted for a change. Less BTV was irradiated using electrons than photons in 29% (CT1) to 37% (CT2). SFB replanning needs to be individualized to each patient because of the variety of factors that can impact dosimetric planning. Replanning is recommended when using 3-field photons if the patient has experienced a ≥5 cm(3) and a ≥25% decrease in LCV during WBI. Some patients may benefit from electron SFB replanning but no tested characteristics reliably predict those who may benefit the most. The amount of BTV irradiated is less with electrons than in photon plans and this has the potential to improve cosmesis, a clinically important outcome in breast-conserving therapy.

High-dose spatially fractionated GRID radiation therapy (SFGRT): a comparison of treatment outcomes with Cerrobend vs. MLC SFGRT.

PURPOSE: Spatially fractionated GRID radiotherapy (SFGRT) using a customized Cerrobend block has been used to improve response rates in patients with bulky tumors. The clinical efficacy of our own multileaf collimator (MLC) technique is unknown. We undertook a retrospective analysis to compare clinical response rates attained using these two techniques. METHODS AND MATERIALS: Seventy-nine patients with bulky tumors (median diameter, 7.6 cm; range, 4-30 cm) treated with SFGRT were reviewed. Between 2003 and late 2005, the Cerrobend block technique (n = 39) was used. Between late 2005 and 2008, SFGRT was delivered using MLC-shaped fields (n = 40). Dose was prescribed to dmax (depth of maximum dose) and was typically 15 Gy. Eighty percent of patients in both groups received external beam radiotherapy in addition to SFGRT. The two-sided Fisher-Freeman-Halton test was used to compare pain and mass effect response rates between the two groups. RESULTS: Sixty-one patients (77%) were treated for palliative intent and 18 (23%) for curative intent. The majority of patients had either lung or head-and-neck primaries in both groups; the most frequent site of SFGRT application was the neck. The majority of patients complained of either pain (65%) or mass effect (58%) at intake. Overall response rates for pain and mass response were no different between the Cerrobend and MLC groups: pain, 75% and 74%, respectively (p = 0.50), and mass effect, 67% and 73%, respectively (p = 0.85). The majority of toxicities were Grade 1 or 2, and only 3 patients had late Grade 3-4 toxicities. CONCLUSIONS: MLC-based and Cerrobend-based SFGRT have comparable and encouraging response rates when used either in the palliative or curative setting. MLC-based SGFRT should allow clinics to more easily adopt this novel treatment approach for the treatment of bulky tumors.

Helical tomotherapy versus single-arc intensity-modulated arc therapy: a collaborative dosimetric comparison between two institutions.

PURPOSE: Both helical tomotherapy (HT) and single-arc intensity-modulated arc therapy (IMAT) deliver radiation using rotational beams with multileaf collimators. We report a dual-institution study comparing dosimetric aspects of these two modalities. METHODS AND MATERIALS: Eight patients each were selected from the University of Maryland (UMM) and the University of Wisconsin Cancer Center Riverview (UWR), for a total of 16 cases. Four cancer sites including brain, head and neck (HN), lung, and prostate were selected. Single-arc IMAT plans were generated at UMM using Varian RapidArc (RA), and HT plans were generated at UWR using Hi-Art II TomoTherapy. All 16 cases were planned based on the identical anatomic contours, prescriptions, and planning objectives. All plans were swapped for analysis at the same time after final approval. Dose indices for targets and critical organs were compared based on dose-volume histograms, the beam-on time, monitor units, and estimated leakage dose. After the disclosure of comparison results, replanning was done for both techniques to minimize diversity in optimization focus from different operators. RESULTS: For the 16 cases compared, the average beam-on time was 1.4 minutes for RA and 4.8 minutes for HT plans. HT provided better target dose homogeneity (7.6% for RA and 4.2% for HT) with a lower maximum dose (110% for RA and 105% for HT). Dose conformation numbers were comparable, with RA being superior to HT (0.67 vs. 0.60). The doses to normal tissues using these two techniques were comparable, with HT showing lower doses for more critical structures. After planning comparison results were exchanged, both techniques demonstrated improvements in dose distributions or treatment delivery times. CONCLUSIONS: Both techniques created highly conformal plans that met or exceeded the planning goals. The delivery time and total monitor units were lower in RA than in HT plans, whereas HT provided higher target dose uniformity.

Improved survival with radiation therapy in high-grade soft tissue sarcomas of the extremities: a SEER analysis.

PURPOSE: The benefit of radiation therapy in extremity soft tissue sarcomas remains controversial. The purpose of this study was to determine the effect of radiation therapy on overall survival among patients with primary soft tissue sarcomas of the extremity who underwent limb-sparing surgery. METHODS AND MATERIALS: A retrospective study from the Surveillance, Epidemiology, and End Results (SEER) database that included data from January 1, 1988, to December 31, 2005. A total of 6,960 patients constituted the study population. Overall survival curves were constructed using the Kaplan-Meir method and for patients with low- and high-grade tumors. Hazard ratios were calculated based on multivariable Cox proportional hazards models. RESULTS: Of the cohort, 47% received radiation therapy. There was no significant difference in overall survival among patients with low-grade tumors by radiation therapy. In high-grade tumors, the 3-year overall survival was 73% in patients who received radiation therapy vs. 63% for those who did not receive radiation therapy (p < 0.001). On multivariate analysis, patients with high-grade tumors who received radiation therapy had an improved overall survival (hazard ratio 0.67, 95% confidence interval 0.57-0.79). In patients receiving radiation therapy, 13.5% received it in a neoadjuvant setting. The incidence of patients receiving neoadjuvant radiation did not change significantly between 1988 and 2005. CONCLUSIONS: To our knowledge, this is the largest population-based study reported in patients undergoing limb-sparing surgery for soft tissue sarcomas of the extremities. It reports that radiation was associated with improved survival in patients with high-grade tumors.

Comparative analysis of the post-lumpectomy target volume versus the use of pre-lumpectomy tumor volume for early-stage breast cancer: implications for the future.

PURPOSE: Three-dimensional conformal accelerated partial breast irradiation (APBI-3D-CRT) is commonly associated with the treatment of large amounts of normal breast tissue. We hypothesized that a planning tumor volume (PTV) generation based on an expansion of the pre-lumpectomy (pre-LPC) intact tumor volume would result in smaller volumes of irradiated normal breast tissue compared with using a PTV based on the post-lumpectomy cavity (post-LPC). Use of PTVs based on the pre-LPC might also result in greater patient eligibility for APBI-3D-CRT. METHODS AND MATERIALS: Forty-one early-stage breast cancers were analyzed. Preoperative imaging was used to determine a pre-LPC tumor volume. PTVs were developed in the pre- and post-LPC settings as per National Surgical Breast and Bowel Project (NSABP)-B39 guidelines. The pre- and post-LPC PTV volumes were compared and eligibility for APBI-3D-CRT determined using NSABP-B39 criteria. RESULTS: The post-LPC PTV exceeded the pre-LPC PTV in all cases. The median volume for the pre- and post-LPC PTVs were 93 cm(3) (range, 24-570 cm(3)) and 250 cm(3) (range, 45-879 cm(3)), respectively, p <0.001. The difference between pre- and post-LPC PTVs represented a median of 165 cc (range, 21-482 cc) or 16% (range, 3%-42%) of the whole breast volume. Three of 41 vs. 13 of 41 cases were ineligible for APBI-3D-CRT when using the pre- and post-LPC PTVs, respectively. CONCLUSION: PTVs based on pre-LPC tumor expansion are likely associated with reduced amounts of irradiated normal breast tissue compared with post-LPC PTVs, possibly leading to greater patient eligibility for APBI-3D-CRT. These findings support future investigation as to the feasibility of neoadjuvant APBI-3D-CRT.

Comparing radiation treatments using intensity-modulated beams, multiple arcs, and single arcs.

PURPOSE: A dosimetric comparison of multiple static-field intensity-modulated radiation therapy (IMRT), multiarc intensity-modulated arc therapy (IMAT), and single-arc arc-modulated radiation therapy (AMRT) was performed to evaluate their clinical advantages and shortcomings. METHODS AND MATERIALS: Twelve cases were selected for this study, including three head-and-neck, three brain, three lung, and three prostate cases. An IMRT, IMAT, and AMRT plan was generated for each of the cases, with clinically relevant planning constraints. For a fair comparison, the same parameters were used for the IMRT, IMAT, and AMRT planning for each patient. RESULTS: Multiarc IMAT provided the best plan quality, while single-arc AMRT achieved dose distributions comparable to those of IMRT, especially in the complicated head-and-neck and brain cases. Both AMRT and IMAT showed effective normal tissue sparing without compromising target coverage and delivered a lower total dose to the surrounding normal tissues in some cases. CONCLUSIONS: IMAT provides the most uniform and conformal dose distributions, especially for the cases with large and complex targets, but with a delivery time similar to that of IMRT; whereas AMRT achieves results comparable to IMRT with significantly faster treatment delivery.

Future directions in neoadjuvant therapy of rectal cancer: maximizing pathological complete response rates.

Neoadjuvant therapy is widely accepted as the current standard of care for localized rectal cancer. Downstaging of disease has been significantly improved and pathological complete response rates (pCR) which were historically below 10% with preoperative radiation alone, now range from 15% to 30% with preoperative chemo-radiation. While the availability of new chemotherapeutic drugs (Irinotecan, Oxaliplatin, etc.) and molecular targeted agents (Bevacizamab, Cetuximab, etc.) hold a great deal of promise, results of recent studies indicate that the pCR rate with neoadjuvant therapy appears to have plateaued at 20-30%. The use of more intensive multidrug combinations has, however, significantly increased the toxicity of treatment. New paradigms in neoadjuvant therapy are therefore needed to further improve results of treatment. This review presents strategies for neoadjuvant therapy, with the potential to improve pCR rates and also survival of patients.

Repeat computed tomography simulation to assess lumpectomy cavity volume during whole-breast irradiation.

PURPOSE: To determine whether the lumpectomy cavity (LPC) decreases in volume during whole-breast radiotherapy (RT) and what factors influence the decrease. PATIENTS AND METHODS: Forty-three women with 44 breast lesions were prospectively enrolled. Eligible patients underwent lumpectomy followed by a CT simulation (CT1) within 60 days of surgery. Patients were treated to the entire breast to a dose of 45-50.4 Gy. After 21-23 treatments, a second planning CT simulation (CT2) was done. The LPC was contoured on CT2, and the volumes (LCV) were compared between CT1 and CT2. RESULTS: The median LCV on CT1 and CT2 was 38.2 cm(3) and 21.7 cm(3), respectively. The median percent change and volume decrease between CT1 and CT2 was -32.0% and 11.2 cm(3), respectively (n = 44). The LCV decreased in 38 of 44 patients (86%). There was a significant correlation between initial LCV and decrease in volume (p = 0.001) and initial LCV and percent decrease in volume (p < 0.001). There was no correlation between time from surgery to CT1, to start of RT, or to CT2 and change in volume. CONCLUSIONS: Patients who undergo lumpectomy almost always have a decrease in their LCV during whole-breast RT. There was a correlation between the initial LCV and decrease in volume on repeat CT simulation. Evaluating patients for this change can potentially lead to decreased doses of radiation to the remaining breast and other critical structures when delivering a small-field boost. Repeat CT simulation should be considered in patients with larger cavities or cavities near critical structures.

The role of radiation therapy in non-small cell lung cancer.

Thoracic irradiation historically plays a strong role in the management of non-small cell lung cancer (NSCLC). Though surgery is the mainstay of early-stage (I and II) disease, adjuvant radiation therapy confers better local control than surgery alone in advanced disease (III). Combining chemotherapy with radiation can help decrease systemic tumor burden and confer an overall survival advantage. Patients with medically inoperable early-stage disease can be treated with radiation alone, and bulky advanced-stage tumors can be treated definitively with platinum-based concurrent chemotherapy and radiation. The success of chemotherapy with radiation together has led to trials of induction treatment for borderline surgical candidates, allowing for downstaging and more complete resection. Local control remains a challenge, and dose escalation as well as more conformal treatment planning studies need to be explored to overcome this problem.