Faculty Bibliography

Pre-operative chemoradiotherapy followed by a total mesorectal excision (TME) is the standard of care for patients with locally advanced (stage II or III) rectal cancer. Approximately 20% of patients may achieve a pathologic complete response after chemoradiation therapy (CRT), which has been shown to be associated with better oncologic outcomes. Whether surgery can be avoided in this population is an area of active investigation. Recent studies demonstrated feasibility and safety of non-operative management in patients with clinical complete response (cCR) after chemoradiotherapy. In this article, we set out to review the current data on non-operative management and to identify areas requiring further investigation, including improvement in imaging for reassessment after CRT and identifying the optimal time frame for restaging. As the field moves forward with non-operative management in select patients with rectal cancer, there continues to be a need to better understand the prognostic factors and biomarkers that may more accurately characterize patients who are qualified for this "wait-and-see" approach and thereby avoid overtreatment, potentially leading to improvements in long-term quality of life.

BACKGROUND:With the continuing increase in the use of definitive stereotactic radiosurgery (SRS) for patients with limited brain metastases (BM), clinicians need more specific prognostic tools. We investigated clinical predictors of outcomes in patients with limited breast cancer BM treated with SRS alone. METHODS AND MATERIALS/METHODS:We identified 136 patients with breast cancer and 1-3 BM who underwent definitive SRS for 186 BM between 2000 and 2012. The Kaplan-Meier method was used to assess overall survival (OS), regional failure (RF), and local failure (LF). Associations between clinical factors and outcomes were tested using Cox regression. A point scoring system was used to stratify patients based on OS, and the predictive power was tested with concordance probability estimate (CPE). RESULTS:The median OS was 17.6 months. The 12-month RF and LF rates were 45% and 10%, respectively. On multivariate analysis, >1 lesion (hazard ratio [HR] = 1.6, P=.02), triple-negative (TN) disease (HR=2.0, P=.006), and active extracranial disease (ED) (HR=2.7, P<.0001) were significantly associated with worse OS. The point score system was defined using proportional simplification of the multivariate Cox proportional hazards regression function. The median OS for patients with 3.0-4.0 points (n=37), 4.5-5.5 points (n=28), 6.0-6.5 points (n=37), and 8-8.5 points (n=34) were 9.2, 15.6, 25.1, and 45.1 months, respectively (P<.0001, CPE = 0.72). Active ED (HR=2.4, P=.0007) was significantly associated with RF. Higher risk for LF was significantly associated with larger BM size (HR=3.1, P=.0001). CONCLUSION/CONCLUSIONS:Patients with >1 BM, active ED, and TN had the highest risk of death after SRS. Active ED is an important prognostic factor for OS and intracranial control.

BACKGROUND AND PURPOSE/OBJECTIVE:To identify clinical and dosimetric factors associated with hematologic toxicity (HT) during chemoradiotherapy for rectal cancer. MATERIALS AND METHODS/METHODS:We analyzed 120 rectal cancer patients treated with neoadjuvant pelvic radiotherapy (PRT) with concurrent 5-fluorouracil-based chemotherapy. The coxal (ilium, ischium, and pubis) bone marrow (BM), sacral BM, and femoral BM were contoured and dose-volume parameters were extracted. Associations between cell count trend and clinical predictors were tested using repeated-measures analysis of variance (ANOVA) test. Associations between clinical variables, Vx (percentage volume receiving x Gy), and cell count ratio at nadir were tested using linear regression models. RESULTS:Nadirs for white blood cell count (WBC), absolute neutrophil count (ANC), and platelets (PLT) occurred in the second week of PRT and the fifth week for hemoglobin and absolute lymphocyte count (ALC). Using cell count ratio, patients treated with 3DCRT had a lower WBC ratio trend during PRT compared to patients treated with IMRT (p=0.04), and patients ⩾59 years of age had a lower hemoglobin ratio trend during PRT (p=0.02). Using absolute cell count, patients treated with 3DCRT had lower ANC cell count trend (p=0.03), and women had lower hemoglobin cell count trend compared to men (p=0.03). On univariate analysis, use of 3DCRT was associated with a lower WBC ratio at nadir (p=0.02). On multiple regression analysis using dosimetric variables, coxal BM V45 (p=0.03) and sacral BM V45 (p=0.03) were associated with a lower WBC and ANC ratio at nadir, respectively. CONCLUSIONS:HT trends during PRT revealed distinct patterns: WBC, ANC, and PLT cell counts reach nadirs early and recover, while hemoglobin and ALC decline steadily. Patients who were treated with 3DCRT and older patients experienced lower cell count ratio trend during PRT. Dosimetric constraints using coxal BM V45 and sacral BM V45 can be considered.

PURPOSE: To evaluate local control after surgical resection and postoperative stereotactic radiosurgery (SRS) for brain metastases. METHODS AND MATERIALS: A total of 49 patients (50 lesions) were enrolled and available for analysis. Eligibility criteria included histologically confirmed malignancy with 1 or 2 intraparenchymal brain metastases, age >/=18 years, and Karnofsky performance status (KPS) >/=70. A Cox proportional hazard regression model was used to test for significant associations between clinical factors and overall survival (OS). Competing risks regression models, as well as cumulative incidence functions, were fit using the method of Fine and Gray to assess the association between clinical factors and both local failure (LF; recurrence within surgical cavity or SRS target), and regional failure (RF; intracranial metastasis outside of treated volume). RESULTS: The median follow-up was 12.0 months (range, 1.0-94.1 months). After surgical resection, 39 patients with 40 lesions were treated a median of 31 days (range, 7-56 days) later with SRS to the surgical bed to a median dose of 1800 cGy (range, 1500-2200 cGy). Of the 50 lesions, 15 (30%) demonstrated LF after surgery. The cumulative LF and RF rates were 22% and 44% at 12 months. Patients who went on to receive SRS had a significantly lower incidence of LF (P=.008). Other factors associated with improved local control include non-small cell lung cancer histology (P=.048), tumor diameter <3 cm (P=.010), and deep parenchymal tumors (P=.036). Large tumors (>/=3 cm) with superficial dural/pial involvement showed the highest risk for LF (53.3% at 12 months). Large superficial lesions treated with SRS had a 54.5% LF. Infratentorial lesions were associated with a higher risk of developing RF compared to supratentorial lesions (P<.001). CONCLUSIONS: Postoperative SRS is associated with high rates of local control, especially for deep brain metastases <3 cm. Tumors >/=3 cm with superficial dural/pial involvement demonstrate the highest risk of LF.

BACKGROUND:This study was conducted to identify the factors associated with acute gastrointestinal (GI) toxicity during pelvic chemoradiotherapy (PCRT) in patients with rectal cancer. METHODS:We analyzed 177 patients with rectal cancer treated from 2007 through 2010. Clinical information, including weekly diarrhea and proctitis toxicity grade during PCRT, was recorded. GI structures including bowel and anal canal were contoured. The associations between toxicity and clinical and dosimetric predictors were tested. RESULTS:The median age was 60; 76 patients were women; 98 were treated with intensity-modulated radiotherapy (IMRT) and 79 with 3D conformal RT (3DCRT). A higher rate of grade 2+ diarrhea was observed in the women, starting at week 4 (24% women vs. 11% men, P = .01; week 5: 33% vs. 12%, P = .002), as well as in all the patients treated with 3DCRT (22% vs. 12% IMRT, P = .03; week 5: 32% vs. 11%, P = .001). On multivariate analysis, the normal tissue complication probability (NTCP) model including bowel V45 (bowel volume receiving ≥45 Gy) showed that being female, and use of 3DCRT, was most predictive of grade 2+ diarrhea (area under the curve [AUC] = 0.76; R S = 0.35; P < .001). A higher rate of grade 2+ proctitis was seen in patients <60 years of age starting at week 3 (21% vs. 9%, P = .02; week 4: 35% vs. 16%, P = .003). The NTCP model including anal canal V15 and younger age was most predictive of grade 2+ proctitis (AUC = 0.67; R S = 0.25; P < .001). CONCLUSIONS:Women and all patients who were treated with 3DCRT had higher rates of grade 2+ diarrhea, and the younger patients had a higher rate of grade 2+ proctitis during PCRT. The use of more stringent dosimetric constraints in higher risk patients is a strategy for minimizing toxicity.

In recent years, accelerated partial breast irradiation (APBI) has been considered an alternative to whole breast irradiation for patients undergoing breast-conserving therapy. APBI delivers higher doses of radiation in fewer fractions to the post-lumpectomy tumor bed with a 1-2 cm margin, targeting the area at the highest risk of local recurrence while sparing normal breast tissue. However, there are inherent challenges in defining accurate target volumes for APBI. Studies have shown that significant interobserver variation exists among radiation oncologists defining the lumpectomy cavity, which raises the question of how to improve the accuracy and consistency in the delineation of tumor bed volumes. The combination of standardized guidelines and surgical clips significantly improves an observer's ability in delineation, and it is the standard in multiple ongoing external-beam APBI trials. However, questions about the accuracy of the clips to mark the lumpectomy cavity remain, as clips only define a few points at the margin of the cavity. This paper reviews the techniques that have been developed so far to improve target delineation in APBI delivered by conformal external beam radiation therapy, including the use of standardized guidelines, surgical clips or fiducial markers, pre-operative computed tomography imaging, and additional imaging modalities, including magnetic resonance imaging, ultrasound imaging, and positron emission tomography/computed tomography. Alternatives to post-operative APBI, future directions, and clinical recommendations were also discussed.

Radiation therapy (RT) plays an essential role in the management of breast cancer by eradicating subclinical disease after surgical removal of grossly evident tumor. Radiation reduces local recurrence rates and increases breast cancer-specific survival in patients with early-stage breast cancer after breast-conserving surgery and in node-positive patients who have undergone mastectomy. This article reviews the following topics: (1) the rationale for adjuvant RT and the evidence for its use in noninvasive and invasive breast cancer, (2) RT delivery techniques for breast-conserving therapy such as hypofractionated RT, partial breast irradiation, and prone irradiation, and (3) indications for PMRT.