Journal of Radiation Oncology

Few studies have evaluated re-irradiation of lung cancer recurrences with stereotactic body radiotherapy (SBRT). This study evaluates outcomes with SBRT re-irradiation for recurrent lung cancer. Two hundred and seventy-eight patients treated with SBRT for lung cancer were retrospectively reviewed. Of those, 26 patients with 29 tumors were re-irradiated with SBRT. Ninety percent of tumors received prior external beam irradiation and 10 % received prior SBRT. Previous median radiation dose was 61.2 Gy with a median 8-month interval from previous radiation. The median re-irradiation SBRT dose was 30 Gy (48 Gy10 biological effective dose (BED)). Endpoints evaluated included local control, overall survival, and progression-free survival. Twenty-five of 29 tumors were evaluable for local control, with 27 tumors (93 %) considered in-field recurrences. In-field crude local control rate was 80 % (20/25) with 1 and 2-year actuarial rates of 78.6 and 65.5 %, respectively. One and 2-year actuarial survival rates were 52.3 and 37.0 %, respectively. One and 2-year actuarial progression-free survival rates were 56.7 and 37.0 %, respectively. Fifty-five percent of patients reported acute/chronic grades 1 and 2 toxicities. No grade 3 or higher toxicities were reported. Patients with recurrent lung cancer have limited options. SBRT re-irradiation is tolerable even after a median 61.2 Gy to the re-irradiation site. The lower BED used provided acceptable progression-free survival with low toxicity. Given the poor prognosis with current treatment options, new paradigms for re-treatment should include SBRT-re-irradiation as an adjunct to systemic therapy for in-field lung cancer recurrence.

The complications as a result of re-irradiation (re-RT) for recurrent head and neck cancer (HNC) can be devastating to the already very ill patient. We sought to examine the pattern of failure with the goal of designing optimal re-RT fields for these patients. From July 1996 to April 2011, 47 HNC patients treated with fractionated re-RT developed locoregional failure. Recurrence sites were oropharynx (n = 12), neck (n = 11), oral cavity (n = 9), larynx (n = 5), paranasal sinuses (n = 5), parotid (n = 4), and hypopharynx (n = 1). Median initial radiation therapy (RT) dose was 65 Gy and median time between radiations was 32.2 months. Salvage surgery was performed in 21 patients (45 %), and 37 patients (79 %) received concurrent chemotherapy. Median re-RT dose was 60 Gy, and all patients received intensity-modulated RT. Patterns of failure were assessed by reviewing target volume delineation and compared slice-by-slice visually alongside axial imaging documenting locoregional recurrence. There was no intention to encompass prophylactic subclinical regions at risk. Coding of failures was either in-field (InF) or out-of-field (OutF). All others were marginal failures (margF). With a median follow-up of 24.5 months, the median time to locoregional progression-free survival (LRPFS) was 5.3 months and median overall survival (OS) was 12.5 months. Failures were documented as InF in 42 patients (89 %), OutF in three patients (6 %), and margF in two patients (4 %). Five patients died while undergoing re-RT. Patients who developed OutF occurred at sites beyond 2 cm from the tumor volume. In our series of recurrent HNC patients who underwent salvage re-RT, the vast majority of locoregional failures were InF. We feel that confining re-RT targets to the gross tumor volume or postoperative clinical target volume without treating the subclinical regions at risk for failure is sufficient. With current image guidance capabilities, reducing the planning target volume margin may further minimize toxicities.

Ductal carcinoma in situ (DCIS) represents a quarter of newly diagnosed breast neoplasms, with the majority of cases detected on routine screening mammography in asymptomatic women. Currently, most women with newly diagnosed DCIS are eligible for breast conserving therapy (BCT); however, significant controversy exists regarding whether or not to add radiation treatment (RT) after surgical excision in low-risk patients. While four older prospective randomized clinical trials have shown that the addition of RT after lumpectomy reduces the risk of ipsilateral breast tumor recurrence (IBTR) by approximately 50 %, recent studies have continued to attempt to identify a subset of patients with favorable risk DCIS who are at a sufficiently low-risk of IBTR that omitting RT might be reasonable. While a number of smaller studies have shown promising results, recent prospective data have consistently affirmed the increased risk of IBTR with the omission of RT, with no subset of patients consistently identified that can be safely observed without RT. While radiation after lumpectomy remains the “standard of care,” even in these low-risk patients, future directions include improvements in genetic assays to better identify low-risk patients and new RT techniques and schedules that can potentially reduce the duration of therapy and toxicity while improving quality of life for patients. Based on the data available, we continue to recommend radiation therapy for low-risk patients with DCIS as no discernible subset has been identified that does not benefit from radiation therapy.

Recognizing spinal cord dose limits in various fractionations is essential to ensure adequate dose for tumor control while minimizing the chance of radiation-induced myelopathy (RIM). This study aimed to determine the α/β ratio of the spinal cord and the cord dose limit in terms of BED50, the biological equivalent dose (BED) that induces 50 % chance of RIM, by fitting data collected from published animal and patient studies. RIM data from five rat studies; three large animal studies on monkeys, dogs, and pigs; and 18 patient studies were included for the investigation. The α/β ratios were derived, respectively, for rat (group A), large animal (group B), patient (group C), and combined data (group D). The α/β ratio (and its 95 % confidental interval) was 4.1 (3.2, 5.0) or 3.6 (2.6, 4.6) Gy for group A, depending on fitting algorithms. It was 3.9 (3.0, 4.8), 3.7 (2.2, 8.2) and 3.9 (3.0, 4.9) for groups B, C, and D, respectively. BED50 was 111 Gy for the combined data. It corresponds to a D50 of 73.4 Gy in 2 Gy/FX, or 19.0 Gy in single fraction. BED5, which is the BED to induce 5 % of RIM, was calculated to be 83.9 Gy. It corresponds to D5 of 55.4 Gy in 2 Gy/FX, or 16.2 Gy in single fraction. The study showed that all four groups had similar α/β ratios close to 3.9 Gy, suggesting that the spinal cord has a similar fractionation effect for different species, including human beings.

Benign tumors of the spine pose unique challenges as they are typically located in proximity to the spinal cord and are relatively radio-resistant. Surgery is usually the first line of treatment, but recurrence can be common. Stereotactic radiosurgery (SRS) is an effective treatment for malignant spine lesions. However, patients with benign tumors generally have longer life expectancies and may develop long-term treatment side-effects. Our institutional experience in treating benign tumors with SRS is presented to display its utility for symptom and local control. A retrospective cohort analysis was performed at a single institution between 2001 and 2013. A total of 26 patients (61 vertebral levels) with benign spine tumors were treated. Electronic medical records were queried for clinical, neurological, and radiological examinations. Post-treatment pain, neurological, and radiographic control were the primary endpoints of this study. Five patients (19.2%) were deceased with a median survival time of 16.9 months. Follow-up to evaluate pain response was available for 23 (88%), neurological for 20 (77%), and radiographic for 23 patients (88%). Median follow-up time was 15.5 months. Total pain response was 82.6%. Neurological improvement and radiographic control were noted in 75 and 87% of patients. One case of radionecrosis of the sacrum and one case of axillary numbness were observed. The results of SRS for benign tumors of the spine appear to be promising, and as a result SRS may have a role in treating benign spinal tumors for patients who are not surgical candidates.

Local failure and subsequent neurologic death continue to be problematic for brain metastases resulting from renal cell carcinoma (RCC), which are highly resistant to whole brain radiation therapy. The objective of this single-institution series is to determine the outcomes of patients with RCC brain metastases treated with stereotactic radiosurgery (SRS). Between January 2005 and December 2011, 51 patients with a total of 104 brain metastases from RCC were treated with linac-based SRS. The median age of this cohort was 60 years (range, 39–82) and consisted of 39 males and 12 females. The average size of the target lesion was 1.6 cc (0.2–82.7) of which 97 (93 %) lesions were treated with a single fraction of 14–24 Gy. Median follow-up for this cohort was 37.5 months. The actuarial 6- and 12-month rates of local control were 89 and 80 %, respectively. By Cox regression analysis, volume was the only predictor of local failure (p = 0.04). Overall survival determined from the time of SRS at 6 and 12 months was 56 and 44 %, respectively. Smaller tumor volume was found to be a significant predictor of improved survival (p = 0.01). None of the patients experienced grade 3 or greater acute or late toxicities. SRS for brain metastases from renal cell carcinoma is a safe and effective treatment resulting in a high rate of local control. To our knowledge, this is the first report demonstrating a relationship between smaller tumor volume and improved outcomes.

We assessed the prognostic value of the interval to biochemical failure (IBF) after salvage radiation therapy (SRT) following radical prostatectomy (RP) for prostate cancer to identify patients at high risk for distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall mortality (OM). From 1991 and 2007, 222 men with T2a-4a, N0/X, M0 prostate cancer received SRT for a rising PSA after RP. Of these, 48 experienced BF. Univariate and multivariate analyses (UVA, MVA, respectively) included initial PSA; T-stage; RT dose; nadir PSA; risk group; IBF; time from surgery to SRT; seminal vesicle invasion; Gleason score; and PSA doubling time. Median follow-up from SRT was 67 months. The median IBF was 33 months (range, 4–96). On UVA, IBF < 12 or <18 months and risk group predicted for DM, PCSM, and OM (p < 0.05). On MVA, IBF < 12 or <18 months predicted for DM (HRs 36.1, 15.3, respectively, p = 0.02). The 5-year DM, PCSM, and OM rates for an IBF of < vs. ≥18 months were 50 vs. 17 %, 45 vs. 0 %, 53 vs. 0 %, respectively (all p < 0.01). Patients with IBF < 18 months are at significantly higher risk of DM and death from prostate cancer. The IBF may be used to guide patients and physicians considering the initiation of salvage ADT. Furthermore, an IBF < 18 months could be used to select “high-risk” patients for clinical trials investigating novel salvage systemic therapy.

This study aims to investigate factors associated with local control and survival benefit of five-fraction stereotactic body radiation therapy (SBRT) for patients with lung malignancies. Patients with pathologically proven malignant lung lesions were treated using SBRT with prescribed dose of 40, 50, and 60 Gy in five fractions. The biologically effective dose assuming α/β ratios of 10 Gy (biologically equivalent doses (BED)10) was 72, 100, and 132 Gy. GTVall and lesion average BED(10), instead of gross tumor volume (GTV) and BED(10), were used in patients with multiple lesions in the overall survival-related factors analysis. GTVall was defined as the sum of all target GTV in treatment, and lesion average BED(10) was defined as the sum of all target BED(10) in treatment divided by number of targets. One hundred and three lesions were treated in 84 patients between June 2004 and June 2008, 69 lesions in 56 patients were eligible in this analysis. No severe (grade >2) toxicities were noted. Two-year local control rates were 92.6%, 100% for primary and recurrent/metastatic groups, respectively. There was no significant factor for local control in univariate and multivariate analyses. One- and 2-year overall survival rates were 96.2%, 45.5%, and 80.0%, 45.6% for the primary and recurrent/metastatic groups, respectively. Multivariate analysis showed that lesion average BED(10) ≥100 and GTVall <20 ml were favorable factors associated with overall survival (P = 0.021 and P = 0.029, respectively). SBRT in five fractions is safe and provides excellent local control for both primary and recurrent/metastatic lung malignancies. BED(10) and tumor volume were shown to be important for overall survival. Additional studies are needed to test the values of lesion average BED(10) and GTVall.