Ronald C. Chen

Internal Mammary Nodes in Breast Cancer: Diagnosis and Implications for Patient Management—A Systematic Review

The management of internal mammary nodes (IMNs) in breast cancer is controversial. Surgical series from the 1950s showed that one third of breast cancer patients had IMN involvement, with a higher risk in patients with medial tumors and/or positive axillary nodes. IMN metastasis has similar prognostic importance as axillary nodal involvement. However, after three randomized trials showed no survival benefit from extended mastectomy compared with radical or modified radical mastectomy, IMN dissection was largely abandoned. Recently, lymphoscintigraphy studies have renewed interest in IMN evaluation. Approximately one fifth of internal mammary sentinel nodes are pathologic, although most centers do not perform IMN biopsies because of concerns about morbidity and lack of established survival benefit. In addition, results from randomized trials testing the value of postmastectomy irradiation and a meta-analysis of 78 randomized trials have provided high levels of evidence that local-regional tumor control is associated with long-term survival improvements. This benefit was limited to trials that used systemic therapy, which was not routinely administered in the earlier surgical studies, although the contribution from IMN treatment is unclear. IMN irradiation has also been shown to cause increased cardiac morbidity. Before mature results from current randomized trials assessing the benefit of IMN irradiation become available, lymphoscintigraphy may be used to help guide decisions regarding systemic and local-regional treatment. However, even in patients with visualized primary IMN drainage, the potential benefit of treatment should be balanced against the risk of added morbidity.

Treatment 'mismatch' in early prostate cancer: Do treatment choices take patient quality of life into account?

Pretreatment urinary, bowel, and sexual dysfunction may increase the toxicity of prostate cancer treatments or preclude potential benefits. Using patient‐reported baseline dysfunction from a prospective cohort study, we determined the proportion of patients receiving relatively contraindicated (‘mismatched’) treatments.

Practice-based evidence to evidence-based practice: Building the national radiation oncology registry

The National Radiation Oncology Registry (NROR), sponsored by the Radiation Oncology Institute and the American Society for Radiation Oncology, is designed to collect standardized information on cancer care delivery among patients treated with radiotherapy in the United States and will focus on patients with prostate cancer. Stakeholders were engaged through a forum that emphasized the need for patient-centered outcomes, minimal data burden, and maximal connectivity to existing registries and databases. An electronic infrastructure is under development to provide connectivity across radiation oncology and hospital information systems. The NROR Gateway features automatic abstraction as well as aggregation of treatment and outcome data. The prostate cancer data dictionary provides standardized elements in four domains: facility, physician, patient, and treatment. The pilot phase will consist of clinical centers chosen to provide a representative mix of radiation treatment modalities, facility types, population-based settings, and regional locations. The initial set of radiation practice metrics includes physician board certification and maintenance, ordering of staging scans, active surveillance discussion, dose prescriptions for low-risk/high-risk disease, radiation fields for low-risk/high-risk disease, image-guided radiation therapy use, androgen deprivation therapy use, post-brachytherapy implant computed tomography dosimetry, collection of toxicity assessments, and longitudinal patient follow-up. The NROR pilot study will provide the framework for expansion to a nationwide electronic registry for radiation oncology.

Dose--volume effects on patient-reported acute gastrointestinal symptoms during chemoradiation therapy for rectal cancer.

PURPOSE Research on patient-reported outcomes (PROs) in rectal cancer is limited. We examined whether dose-volume parameters of the small bowel and large bowel were associated with patient-reported gastrointestinal (GI) symptoms during 5-fluorouracil (5-FU)-based chemoradiation treatment for rectal cancer. METHODS AND MATERIALS 66 patients treated at the Brigham & Womens Hospital or Massachusetts General Hospital between 2006 and 2008 were included. Weekly during treatment, patients completed a questionnaire assessing severity of diarrhea, urgency, pain, cramping, mucus, and tenesmus. The association between dosimetric parameters and changes in overall GI symptoms from baseline through treatment was examined by using Spearmans correlation. Potential associations between these parameters and individual GI symptoms were also explored. RESULTS The amount of small bowel receiving at least 15 Gy (V15) was significantly associated with acute symptoms (p = 0.01), and other dosimetric parameters ranging from V5 to V45 also trended toward association. For the large bowel, correlations between dosimetric parameters and overall GI symptoms at the higher dose levels from V25 to V45 did not reach statistical significance (p = 0.1), and a significant association was seen with rectal pain from V15 to V45 (p < 0.01). Other individual symptoms did not correlate with small bowel or large bowel dosimetric parameters. CONCLUSIONS The results of this study using PROs are consistent with prior studies with physician-assessed acute toxicity, and they identify small bowel V15 as an important predictor of acute GI symptoms during 5-FU-based chemoradiation treatment. A better understanding of the relationship between radiation dosimetric parameters and PROs may allow physicians to improve radiation planning to optimize patient outcomes.

Patient-reported quality of life after salvage brachytherapy for radio-recurrent prostate cancer: A prospective Phase II study.

BACKGROUND Patient-reported quality of life (QOL) after salvage brachytherapy for radiorecurrent prostate cancer has not been well-characterized prospectively. METHODS We examined 25 men who recurred after primary radiotherapy for prostate cancer and received MRI-guided salvage brachytherapy as part of a prospective Phase II study. These patients received prospectively a validated patient-reported QOL questionnaire to fill out at baseline, as well as 3, 15, and 27 months after re-irradiation to determine the degree of sexual, bowel, and urinary dysfunction (maximum dysfunction score=100). RESULTS On average, sexual function continued to decline with time, and patients had significantly worse sexual function scores at 27 months than baseline (p=0.01). Although bowel and urinary symptoms worsened acutely at 3 or 15 months, they showed on average some improvement by 27 months, and there were no significant differences between baseline and 27-month urinary or bowel scores. An interval to re-irradiation less than 4.5 years and prior brachytherapy were each associated significantly with the largest decrements in bowel function (p=0.035). CONCLUSION Similar to the patterns seen in the de novo setting, patients who receive salvage brachytherapy report a worsening of bowel and urinary symptoms followed by some improvement by 27 months, while sexual function steadily declines over time. Interval to re-irradiation and type of prior radiation received may be used to counsel and optimize selection of men for salvage brachytherapy with regard to QOL endpoints.

Reply to J.L. Oh et al

We thank Drs Oh and Buchholz for their letter regarding our review article, emphasizing several important issues on the treatment of internal mammary nodes (IMNs) in breast cancer. As the letter suggests and as we summarized in the article, multiple studies consistently show that a significant minority of patients with breast cancer have pathologic IMN involvement, and the risk of IMN involvement increases in patients with medial tumors and/or positive axillary nodes. While it seems reasonable based on these data to consider IMN irradiation for patients with medial tumors and/or positive axillary nodes, evidence directly linking IMN treatment to a survival benefit is not currently available. Randomized trials evaluating IMN dissection did not show a survival benefit, although they were largely underpowered, and retrospective studies evaluating patients with versus without IMN treatment have shown mixed results. We eagerly await results from more recent randomized trials assessing the potential benefit of IMN irradiation to help shed light on this question. Before these data become available, considerations regarding IMN treatment must include its potential therapeutic benefits balanced against a possible risk of increased morbidity. Drs Oh and Buchholz highlight modern radiation treatment techniques for the IMN, including their elegant split-electron beam technique. Indeed, while the older radiation techniques using an anterior photon field or “Hockey Stick” technique to treat the IMN exposed a significant portion of the heart to radiation treatment, modern computed tomography–based planning have allowed the development of multiple techniques that cover the IMN but minimize radiation dose to the heart. As the letter correctly points out, the Danish Breast Cancer Cooperative Group trials 82b and 82c, which used an electron technique to treat the IMN, showed no increase in the rate of deaths from ischemic heart disease (0.9%) in patients randomly assigned to the radiation therapy arm. We agree that current concerns about potential cardiac morbidity and mortality risk from IMN irradiation should not be completely based on outcomes of outdated radiation techniques from 20 to 30 years ago. More studies are needed to evaluate the long-term cardiac effects of modern radiation techniques. Specifically, an especially important area of research is studies that help clarify the relationship between dose/volume of heart-irradiated and long-term cardiac morbidity/mortality, which is not currently well understood. In addition, how radiation treatment to specific portions of the heart changes cardiac physiology also needs to be defined. Such information could allow IMN irradiation to be administered even more safely.