Optimal Radiation Therapy Fractionation Regimens for Early-Stage Non-Small Cell Lung Cancer.

PURPOSE: A series of radiobiological models were developed to study tumor control probability (TCP) for stereotactic body radiation therapy (SBRT) of early-stage non-small cell lung cancer (NSCLC) per the Hypofractionated Treatment Effects in the Clinic (HyTEC) working group. This study was conducted to further validate 3 representative models with the recent clinical TCP data ranging from conventional radiation therapy to SBRT of early-stage NSCLC and to determine systematic optimal fractionation regimens in 1 to 30 fractions for radiation therapy of early-stage NSCLC that were found to be model-independent. METHODS AND MATERIALS: Recent clinical 1-, 2-, 3-, and 5-year actuarial or Kaplan-Meier TCP data of 9808 patients from 56 published papers were collected for radiation therapy of 2 to 4 Gy per fraction and SBRT of early-stage NSCLC. This data set nearly triples the original HyTEC sample, which was used to further validate the HyTEC model parameters determined from a fit to the clinical TCP data. RESULTS: TCP data from the expanded data set are well described by the HyTEC models with α/ß ratios of about 20 Gy. TCP increases sharply with biologically effective dose and reaches an asymptotic maximal plateau, which allows us to determine optimal fractionation schemes for radiation therapy of early-stage NSCLC. CONCLUSIONS: The HyTEC radiobiological models with α/ß ratios of about 20 Gy determined from the fits to the clinical TCP data for SBRT of early-stage NSCLC describe the recent TCP data well for both radiation therapy of 2 to 4 Gy per fraction and SBRT dose and fractionation schemes of early-stage NSCLC. A steep dose response exists between TCP and biologically effective dose, and TCP reaches an asymptotic maximum. This feature results in model-independent optimal fractionation regimens determined whenever safe for SBRT and hypofractionated radiation therapy of early-stage NSCLC in 1 to 30 fractions to achieve asymptotic maximal tumor control, and T2 tumors require slightly higher optimal doses than T1 tumors. The proposed optimal fractionation schemes are consistent with clinical practice for SBRT of early-stage NSCLC.

Long-Term Outcomes From a Phase 2 Trial of Radiofrequency Ablation Combined With External Beam Radiation Therapy for Patients With Inoperable Non-Small Cell Lung Cancer.

PURPOSE: Long-term outcomes after external beam radiation therapy (EBRT) and radiofrequency ablation (RFA) for medically inoperable early-stage non-small cell lung cancer (NSCLC) are not well known. METHODS AND MATERIALS: Patients with medically inoperable early-stage NSCLC were enrolled in a prospective single-arm, phase 2 study between June 2007 and October 2008 and were treated with RFA followed by EBRT. Radiation was delivered using hypofractionated radiation therapy (HFRT; 70.2 Gy in 26 fractions) or stereotactic body radiation therapy (54 Gy in 3 fractions). RESULTS: Twelve patients were evaluable; 10 patients were treated with HFRT. The cumulative incidence of local progression at 5 years was 16.7% (95% confidence interval [CI], 0-37.8). Median progression-free survival was 37.8 months (95% CI, 11.1 to not reached) and median overall survival was 53.6 months (95% CI, 21.0 to not reached). There were no mortalities within 30 days after RFA and no grade ≥4 toxicity. CONCLUSIONS: The combination of RFA with EBRT appears feasible with favorable long-term local control. However, because SBRT alone has similar or better rates of control, we do not recommend routine combined RFA and EBRT.

Stereotactic body radiotherapy for an isolated splenic metastasis from ovarian carcinoma.

Splenic metastases from oligometastatic ovarian carcinoma are a rare occurrence. Usual treatment for splenic metastases includes splenectomy, but some patients are either unable or unwilling to undergo surgery. Stereotactic body radiotherapy (SBRT) is an effective ablative modality for treating metastatic disease. SBRT to abdominopelvic tumors has been shown to be safe and effective for properly-selected patients and is particularly attractive in the oligometastatic setting as an alternative to radical resection. In this case study, we report a patient with an isolated splenic metastasis from ovarian carcinoma treated with 50 Gy in 10 fractions.

Cartilage oligomeric matrix protein in patients with osteoarthritis is independently associated with metastatic disease in prostate cancer.

Metastatic prostate cancer has a 5-year survival rate of 30%. Identifying predictors of metastasis outcome could potentially reduce patient mortality. The objective of this study was to determine whether osteoarthritis had an impact on outcomes of prostate cancer including death, local recurrence and/or metastasis and to determine whether cartilage oligomeric matrix protein was involved. We performed a retrospective case-control study of patients with prostate cancer with and without the diagnosis of osteoarthritis and completed immunohistochemistry (IHC) analysis of prostate (n=20) and lymph node (n=7) surgical specimens. We evaluated death, local recurrence and metastatic disease by various IHC biomarkers including prostate specific membrane antigen (PSMA), cartilage oligomeric matrix protein (COMP), CD31, and Ki-67. Our model identified osteoarthritis as an independent risk factor for metastatic disease (OR 5.24, 95% CI 1.49 - 18.41). Most notably, when joint arthroplasty was included in the model, osteoarthritis was no longer an independent risk factor for this outcome (p=0.071). IHC demonstrated that those with osteoarthritis, had greater expression of COMP in the prostate samples (mean 23.9% vs 5.84%, p<0.05) but not of Ki-67, CD31, or PSMA. This study identified and quantified increased metastatic disease in patients with osteoarthritis. Also, patients with osteoarthritis expressed increased COMP levels in the prostate and most likely in distant lymphatic nodes. Moreover, our findings suggest that joint arthroplasty may affect the ability of osteoarthritis to promote metastasis, which could impact treatment protocols and survival outcomes of the most common cause of cancer-related death (metastasis) in the United States.

Limited-Stage Small Cell Lung Cancer: Is Prophylactic Cranial Irradiation Necessary?

PURPOSE: Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases in patients with limited stage small cell lung cancer (LS-SCLC). However, PCI is associated with neurotoxicity. Previous studies have not consistently used pretreatment magnetic resonance imaging. Modern imaging improvements continue to enhance early metastasis detection, potentially decreasing the utility of PCI. We sought to determine whether PCI was associated with improved outcomes in LS-SCLC patients with modern imaging. METHODS AND MATERIALS: We identified LS-SCLC patients with no intracranial disease who were treated between 2007 and 2018. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated and multivariate Cox proportional hazards models were generated. The cumulative incidence of brain metastases was estimated using competing risks methodology. RESULTS: Ninety-two patients were identified without intracranial disease at initial staging, 39 of whom received PCI. Median follow-up was 56.7 months. The median OS for the cohort was 35.5 months (95% CI, 25.8-49.3), and median PFS was 19.1 months (95% CI, 12.3-30.5). Median OS with PCI versus observation was 37.9 months (95% CI, 31.8-not reached) versus 30.5 months (95% CI, 14.6-56.1; P = .07), whereas median PFS was 26.3 months (95% CI 19.1-not reached) versus 12.3 months (95% CI, 8.5-30.5; P = .02), respectively. Overall, at 2 years, the cumulative incidence of brain metastases was 10% with PCI and 29% without; this increased to 32% and 29% by 4 years (P = .66). In those patients who had negative magnetic resonance imaging of the brain after completing initial treatment, the 1-year cumulative incidence of brain metastasis was not significantly different at 8% versus 11% (P = .46) respectively. Both PCI and treatment response were independent predictors for PFS on multivariate analysis. Stratified by disease response, patients with a complete response did not benefit from PCI (P = .50), whereas those with partial response or stable disease experienced improved PFS (P = .01). CONCLUSIONS: Overall, PCI was associated with improved PFS and reduced early incidence of brain metastases. Patients achieving a complete response to initial therapy did not experience a PFS benefit with PCI. This may indicate that subsets of LS-SCLC patients can potentially be spared from PCI in the era of modern imaging.

Simple and Rapid Creation of Customized 3-dimensional Printed Bolus Using iPhone X True Depth Camera.

PURPOSE: Three-dimensional printing has produced customized bolus during radiation therapy for superficial tumors along irregular skin surfaces. In comparison, traditional bolus materials are often difficult to manipulate for a proper fit. Current 3-dimensional printed boluses are made from either preexisting computed tomography scans or complex surface scanning methods. Herein, we introduce an inexpensive, convenient approach to generate a 3-dimensional printed bolus from surface scanning technology available in common smartphones. METHODS AND MATERIALS: A three-dimensional printed bolus was designed using surface scans from iPhone X true depth cameras and a low-cost 3-dimensional printer. The percentage density infill was adjusted to achieve tissue equivalence. To evaluate the clinical feasibility, fit against the skin surface and radiation dose distribution were compared with those of the traditional bolus. RESULTS: We fabricated a customized 3-dimensional printed bolus for different areas of the face using an iPhone X camera and inexpensive commercially available 3-dimensional printer. When printed at 100% density, the bolus material approximated soft tissue/water and provided an equivalent dose distribution to that found with standard bolus materials on direct comparison. The bolus material is inexpensive and produces an ideal fit with the scanned anatomy. CONCLUSIONS: We present a simplified method of highly customized bolus production that requires minimal experience with computer modeling programs and can be accomplished with an iPhone true depth camera.

Oncology Navigation Decreases Time to Treatment in Patients with Pancreatic Malignancy.

BACKGROUND: Care of pancreatic cancer patients has become increasingly complex, which has led to delays in the initiation of therapy. Nurse navigators have been added to care teams, in part, to ameliorate this delay. This study investigated the difference in time from first oncology visit to first treatment date in patients with any pancreatic malignancy before and after the addition of an Oncology Navigator. METHODS: A single-institution database of patients with any pancreatic neoplasm evaluated by a provider in radiation, medical, or surgical oncology between 1 October 2015 and 30 September 2017 was analyzed. After 1 October 2016, an Oncology Navigator met patients at their initial visit and coordinated care throughout treatment. The cohort was divided into two groups: patients evaluated prior to the implementation of an Oncology Navigator and patients evaluated after implementation. Patient demographics and time from first visit to first intervention were compared. RESULTS: Overall, 147 patients with a new diagnosis of pancreatic neoplasm were evaluated; 57 patients were seen prior to the start of the Oncology Navigator program and 79 were evaluated after the navigation program was implemented. On univariate analysis, time from first contact by any provider to intervention was 46 days prior to oncology navigation and 26 days after implementation of oncology navigation (p = 0.005). While controlling for other covariates, employment of the Oncology Navigator decreased the time from first contact by any provider to intervention by almost 16 days (p = 0.009). CONCLUSIONS: Implementing an oncology navigation program significantly decreased time to treatment in patients with pancreatic malignancy.

Long-Term Outcomes of a Phase 2 Trial of Chemotherapy With Consolidative Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer.

PURPOSE: Recent data indicate consolidative radiation therapy improves progression-free survival (PFS) for patients with oligometastatic non-small cell lung cancer (NSCLC). Data on long-term outcomes are limited. METHODS AND MATERIALS: This prospective, multicenter, single-arm, phase 2 trial was initiated in 2010 and enrolled patients with oligometastatic NSCLC. Oligometastatic disease was defined as a maximum of 5 metastatic lesions for all disease sites, including no more than 3 active extracranial metastatic lesions. Limited mediastinal lymph node involvement was allowed. Patients achieving a partial response or stable disease after 3 to 6 cycles of platinum-based chemotherapy were treated with CRT to the primary and metastatic sites of disease, followed by observation alone. The primary endpoint was PFS, with secondary endpoints of local control, overall survival (OS), and safety. RESULTS: Twenty-nine patients were enrolled between October 2010 and October 2015, and 27 were eligible for consolidative radiation therapy. The study was closed early because of slow accrual but met its primary endpoint for success, which was PFS >6 months (P < .0001). The median PFS (95% confidence interval) was 11.2 months (7.6-15.9 months), and the median OS was 28.4 months (14.5-45.8 months). Survival outcomes were not significantly different for patients with brain metastases (P = .87 for PFS; P = .12 for OS) or lymph node involvement (P = .74 for PFS; P = .86 for OS). CONCLUSIONS: For patients with oligometastatic NSCLC, chemotherapy followed by consolidative radiation therapy without maintenance chemotherapy was associated with encouraging long-term outcomes.

Cortical Thinning and Structural Bone Changes in Non-Human Primates after Single-Fraction Whole-Chest Irradiation.

Stereotactic body radiation therapy (SBRT) is associated with an increased risk of vertebral compression fracture. While bone is typically considered radiation resistant, fractures frequently occur within the first year of SBRT. The goal of this work was to determine if rapid deterioration of bone occurs in vertebrae after irradiation. Sixteen male rhesus macaque non-human primates (NHPs) were analyzed after whole-chest irradiation to a midplane dose of 10 Gy. Ages at the time of exposure varied from 45-134 months. Computed tomography (CT) scans were taken 2 months prior to irradiation and 2, 4, 6 and 8 months postirradiation for all animals. Bone mineral density (BMD) and cortical thickness were calculated longitudinally for thoracic (T) 9, lumbar (L) 2 and L4 vertebral bodies; gross morphology and histopathology were assessed per vertebra. Greater mortality (related to pulmonary toxicity) was noted in NHPs <50 months at time of exposure versus NHPs >50 months ( P = 0.03). Animals older than 50 months at time of exposure lost cortical thickness in T9 by 2 months postirradiation ( P = 0.0009), which persisted to 8 months. In contrast, no loss of cortical thickness was observed in vertebrae out-of-field (L2 and L4). Loss of BMD was observed by 4 months postirradiation for T9, and 6 months postirradiation for L2 and L4 ( P < 0.01). For NHPs younger than 50 months at time of exposure, both cortical thickness and BMD decreased in T9, L2 and L4 by 2 months postirradiation ( P < 0.05). Regions that exhibited the greatest degree of cortical thinning as determined from CT scans also exhibited increased porosity histologically. Rapid loss of cortical thickness was observed after high-dose chest irradiation in NHPs. Younger age at time of exposure was associated with increased pneumonitis-related mortality, as well as greater loss of both BMD and cortical thickness at both in- and out-of-field vertebrae. Older NHPs exhibited rapid loss of BMD and cortical thickness from in-field vertebrae, but only loss of BMD in out-of-field vertebrae. Bone is sensitive to high-dose radiation, and rapid loss of bone structure and density increases the risk of fractures.

Classification for long-term survival in oligometastatic patients treated with ablative radiotherapy: A multi-institutional pooled analysis.

BACKGROUND: Radiotherapy is increasingly used to treat oligometastatic patients. We sought to identify prognostic criteria in oligometastatic patients undergoing definitive hypofractionated image-guided radiotherapy (HIGRT). METHODS: Exclusively extracranial oligometastatic patients treated with HIGRT were pooled. Characteristics including age, sex, primary tumor type, interval to metastatic diagnosis, number of treated metastases and organs, metastatic site, prior systemic therapy for primary tumor treatment, prior definitive metastasis-directed therapy, and systemic therapy for metastasis associated with overall survival (OS), progression-free survival (PFS), and treated metastasis control (TMC) were assessed by the Cox proportional hazards method. Recursive partitioning analysis (RPA) identified prognostic risk strata for OS and PFS based on pretreatment factors. RESULTS: 361 patients were included. Primary tumors included non-small cell lung (17%), colorectal (19%), and breast cancer (16%). Three-year OS was 56%, PFS was 24%, and TMC was 72%. On multivariate analysis, primary tumor, interval to metastases, treated metastases number, and mediastinal/hilar lymph node, liver, or adrenal metastases were associated with OS. Primary tumor site, involved organ number, liver metastasis, and prior primary disease chemotherapy were associated with PFS. OS RPA identified five classes: class 1: all breast, kidney, or prostate cancer patients (BKP) (3-year OS 75%, 95% CI 66-85%); class 2: patients without BKP with disease-free interval of 75+ months (3-year OS 85%, 95% CI 67-100%); class 3: patients without BKP, shorter disease-free interval, ≤ two metastases, and age < 62 (3-year OS 55%, 95% CI 48-64%); class 4: patients without BKP, shorter disease-free interval, ≥ three metastases, and age < 62 (3-year OS 38%, 95% CI 24-60%); class 5: all others (3-year OS 13%, 95% CI 5-35%). Higher biologically effective dose (BED) (p < 0.01) was associated with OS. CONCLUSIONS: We identified clinical factors defining oligometastatic patients with favorable outcomes, who we hypothesize are most likely to benefit from metastasis-directed therapy.

An Intergroup Randomized Phase II Study of Bevacizumab or Cetuximab in Combination with Gemcitabine and in Combination with Chemoradiation in Patients with Resected Pancreatic Carcinoma: A Trial of the ECOG-ACRIN Cancer Research Group (E2204).

OBJECTIVES: Evaluate toxicity of two treatment arms, A (cetuximab) and B (bevacizumab), when combined with gemcitabine, and chemoradiation in patients with completely resected pancreatic carcinoma. Secondary objectives included overall survival (OS) and disease-free survival (DFS). METHODS: Patients with R0/R1 resection were randomized 1:1 to cetuximab or bevacizumab administered in combination with gemcitabine for two treatment cycles. Next three cycles included concurrent cetuximab/bevacizumab plus chemoradiation, followed by one cycle of cetuximab/bevacizumab. Cycles 7-12 included cetuximab/bevacizumab with gemcitabine. Cycles were 2 weeks. Frequency of specific toxicities was summarized for each treatment arm at two times during the study, after chemotherapy but prior to chemoradiation and after all therapy. RESULTS: A total of 127 patients were randomized (A, n = 65; B, n = 62). Prior to chemoradiation, the overall rate for toxicities of interest was 10% for arm A and 2% for arm B. After all therapy, the overall rates for toxicities of interest were 30 and 25% for arms A and B, respectively. Overall median OS and DFS were 17 and 11 months, respectively, which is not a significant improvement over expected survival rates for historical controls. CONCLUSIONS: Both treatments were tolerable with manageable toxicities, and were safe enough for a phase III trial had this been indicated.

Early dose-dependent cortical thinning of the femoral neck in anal cancer patients treated with pelvic radiation therapy.

BACKGROUND AND PURPOSE: Anal cancer patients treated with radiation therapy (RT) have an increased risk of hip fractures after treatment. The mechanism of these fractures is unknown; however, femoral fractures have been correlated with cortical bone thinning. The objective of this study was to assess early changes in cortical bone thickness at common sites of femoral fracture in anal cancer patients treated with intensity modulated radiation therapy (IMRT). MATERIALS AND METHODS: RT treatment plans and computed tomography (CT) scans from 23 anal cancer patients who underwent IMRT between November 2012 and December 2014 were retrospectively reviewed. Cortical thickness (Ct.Th) was mapped at homologous vertices within the proximal femur using pre-RT and post-RT (≤4months) CT scans. The bone attenuation measurements were collected at homologous locations within the trabecular bone of the right femoral neck (FN). The percent change in Ct.Th and trabecular bone mineral density (trBMD) were assessed. FN cortical thinning was correlated to RT dose using linear regression. A logistic model for dose dependent cortical thinning was constructed. RESULTS: Twenty-two patients were analyzed. Significant post-treatment cortical thinning was observed in the intertrochanteric crest, subcapital and inferior FN (p<0.05). FN volume receiving ≥40Gy (V40Gy) was a significant predictor of focal cortical thinning ≥30% (p=0.03). A significant decrease in FN trBMD was observed (-6.4% [range -34.4 to 3.3%]; p=0.01). CONCLUSION: Significant early decrease in Ct.Th and trBMD occurs at the FN in patients treated with RT for anal cancer. FN V40Gy was predictive of clinically significant focal FN cortical thinning.

A cortical thickness and radiation dose mapping approach identifies early thinning of ribs after stereotactic body radiation therapy.

BACKGROUND AND PURPOSE: High rates of spontaneous rib fractures are associated with thoracic stereotactic body radiation therapy (SBRT). These fractures likely originate within the cortical bone and relate to the cortical thickness (Ct.Th). We report the development and application of a novel Ct.Th and radiation dose mapping technique to assess early site-specific changes of cortical bone in ribs. MATERIALS AND METHODS: Rib Ct.Th maps were constructed from pre-SBRT and 3month post-SBRT CT scans for 28 patients treated for peripheral lung lesions. The Ct.Th at approximately 50,000 homologous points within the entire rib cage was determined pre- and post-SBRT. Each rib was then divided into 30 homologous regions. The mean dose and thinning were determined per section. RESULTS: Regions of ribs that received ⩾10Gy exhibited significant thinning of cortical bone (p=0.001). The mean Ct.Th percent difference (95% CI) in regions receiving 10-20Gy, 20-30Gy, 30-40Gy, and ⩾40Gy were -7% (-4%,-11%), -14% (-18%,-11%), -15% (-19%,-11%), and -18% (-22%,-15%) respectively. Regions receiving >20Gy experienced significantly more thinning than regions receiving lower doses. CONCLUSIONS: Substantial early cortical bone thinning was observed post-SBRT in regions of ribs that received ⩾10Gy. The rapid thinning of ribs may predispose ribs to fracture after SBRT.

ACR Appropriateness Criteria® Local Excision in Early Stage Rectal Cancer.

Low anterior resection or abdominoperineal resection are considered standard treatments for early rectal cancer but may be associated with morbidity in selected patients who are candidates for early distal lesions amenable to local excision (LE). The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel recognizes the importance of accurate staging to identify patients who may be candidates for a LE approach. Patients who may be candidates for LE alone include those with small, low-lying T1 tumors, without adverse pathologic features. Several surgical approaches can be utilized for LE however none include lymph node evaluation. Adjuvant radiation±chemotherapy may be warranted depending on the risk of nodal metastases. Patients with high-risk T1 tumors, T2 tumors not amenable to radical surgery may also benefit from adjuvant treatment; however, patients with positive margins or T3 lesions should be offered abdominoperineal resection or low anterior resection. Neoadjuvant radiation±chemotherapy followed by LE in higher risk patients results in excellent local control, but it is not clear if this approach reduces recurrence rates over surgery alone.

ACR Appropriateness Criteria® Resectable Stomach Cancer.

For resectable gastric cancer, perioperative chemotherapy or adjuvant chemoradiation with chemotherapy are standards of care. The decision making for adjuvant therapeutic management can depend on the stage of the cancer, lymph node positivity, and extent of surgical resection. After gastric cancer resection, postoperative chemotherapy combined with chemoradiation should be incorporated in cases of D0 lymph node dissection, positive regional lymph nodes, poor clinical response to induction chemotherapy, or positive margins. In the setting of a D2 lymph node dissection, especially those with negative regional lymph nodes, adjuvant chemotherapy alone could be considered. The American College of Radiology (ACR) Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

The multidisciplinary approach to the treatment of rectal cancer: 2015 update.

The multidisciplinary approach to the management of rectal cancer continues to evolve with developments in surgery, radiation therapy as well as systemic chemotherapy. Refinement of surgical techniques to improve organ preservation, selective use of neoadjuvant (or adjuvant) therapies, improvements in staging modalities and emerging criteria for the selection of tailored therapies are some of the advancements made over the last three decades. In addition, neoadjuvant treatment alternatives, multimodality sequencing and adaptive therapies based on treatment response continue to be a subject of clinical investigation. The current article reviews the salient topics related to the multidisciplinary treatment of resectable rectal cancer.

ACR Appropriateness Criteria® rectal cancer: metastatic disease at presentation.

The management of rectal cancer in patients with metastatic disease at presentation is highly variable. There are no phase III trials addressing therapeutic approaches, and the optimal sequencing of chemotherapy, radiation therapy, and surgery remains unresolved. Although chemoradiation is standard for patients with stage II/III rectal cancer, its role in the metastatic setting is controversial. Omitting chemoradiation may not be appropriate in all stage IV patients, particularly those with symptomatic primary tumors. Moreover, outcomes in this setting are vastly different, as some treatments carry the potential for cure in selected patients, while others are purely palliative. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application, by the panel, of a well-established consensus methodology (Modified Delphi) to rate the appropriateness of imaging and treatment procedures. In instances in which evidence is lacking or not definitive, expert opinion may be used as the basis for recommending imaging or treatment.

Comparison of accelerated hypofractionation and stereotactic body radiotherapy for Stage 1 and node negative Stage 2 non-small cell lung cancer (NSCLC).

PURPOSE: Stereotactic body radiation therapy (SBRT) and accelerated hypofractionated radiation therapy (AHRT) have favorable local control (LC) relative to conventional fractionation in the treatment of stage I non-small cell lung cancer (NSCLC). We report the results of our single institution experience with the treatment of early stage NSCLC with SBRT or AHRT in cases where SBRT was felt to be suboptimal. METHODS: One hundred and sixty patients with Stage 1 and node negative Stage 2 NSCLC were treated with SBRT or AHRT from 2003 to 2011. Median follow-up was 29.4 and 19 months (mo), respectively. The median dose was 54Gy in 3 fractions (fx) (SBRT) and 70.2Gy in 26 fx (AHRT). Acute and late toxicities (tox) were graded (G) per CTCAE v4. Time to local (LF), regional (RF) and distant (DF) failure were estimated using the Kaplan-Meier method. The impact of patient and tumor related factors on LF were estimated by multivariate Cox proportional hazard model. RESULTS: Three-year LC rates were 87.7% (SBRT) and 71.7% (AHRT). The 3-year freedom from DF was 73.3% and 68.1%. Median OS was 38.4 (95% CI 29.7-51.6) and 35 (95% CI 22-48.3) mo. No G3 or 4 tox were observed. At 1 year, 30% and 50% of complications resolved, while (5-6%) had persistent chest wall pain. Multivariate analysis demonstrated that increasing dose per fraction and tumor size (>5.5 vs. 4cm) in the AHRT and SBRT group were found to be associated with a reduced (HR 0.33 95% CI 0.13-0.84, p=0.021) and increased (HR: 6.372 95% CI 1.23-32.92, p=0.027) hazard for local failure respectively. CONCLUSIONS: Our results compare favorably with other reports of treatment for early stage NSCLC. AHRT patients had comparable LC despite increased size and central disease. Toxicity was limited and overall survival, regional and distant recurrences were similar between groups.

Management of mediastinal relapse after treatment with stereotactic body radiotherapy or accelerated hypofractionated radiotherapy for stage I/II non-small-cell lung cancer.

PURPOSE/OBJECTIVE(S): Regional failures occur in up to 15% of patients treated with stereotactic body radiotherapy (SBRT) for stage I/II lung cancer. This report focuses on the management of the unique scenario of isolated regional failures. METHODS: Patients treated initially with SBRT or accelerated hypofractionated radiotherapy were screened for curative intent treatment of isolated mediastinal failures (IMFs). Local control, regional control, progression-free survival, and distant control were estimated from the date of salvage treatment using the Kaplan-Meier method. RESULTS: Among 160 patients treated from 2002 to 2012, 12 suffered IMF and were amenable to salvage treatment. The median interval between treatments was 16 months (2-57 mo). Median salvage dose was 66 Gy (60-70 Gy). With a median follow-up of 10 months, the median overall survival was 15 months (95% confidence interval, 5.8-37 mo). When estimated from original treatment, the median overall survival was 38 months (95% confidence interval, 17-71 mo). No subsequent regional failures occurred. Distant failure was the predominant mode of relapse following salvage for IMF with a 2-year distant control rate of 38%. At the time of this analysis, three patients have died without recurrence while four are alive and no evidence of disease. High-grade toxicity was uncommon. CONCLUSIONS: To our knowledge, this is first analysis of salvage mediastinal radiation after SBRT or accelerated hypofractionated radiotherapy in lung cancer. Outcomes appear similar to stage III disease at presentation. Distant failures were common, suggesting a role for concurrent or sequential chemotherapy. A standard full course of external beam radiotherapy is advisable in this unique clinical scenario.

ACR Appropriateness Criteria®-Anal Cancer.

The management of anal cancer is driven by randomized and nonrandomized clinical trials. However, trials may present conflicting conclusions. Furthermore, different clinical situations may not be addressed in certain trials because of eligibility inclusion criteria. Although prospective studies point to the use of definitive 5-fluorouracil and mitomycin C-based chemoradiation as a standard, some areas remain that are not well defined. In particular, management of very early stage disease, radiation dose, and the use of intensity-modulated radiation therapy remain unaddressed by phase III studies. The American College of Radiology (ACR) Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.