Jiho Nam

Radiotherapy Dose–Volume Effects on Salivary Gland Function

Publications relating parotid dose-volume characteristics to radiotherapy-induced salivary toxicity were reviewed. Late salivary dysfunction has been correlated to the mean parotid gland dose, with recovery occurring with time. Severe xerostomia (defined as long-term salivary function of <25% of baseline) is usually avoided if at least one parotid gland is spared to a mean dose of less than approximately 20 Gy or if both glands are spared to less than approximately 25 Gy (mean dose). For complex, partial-volume RT patterns (e.g., intensity-modulated radiotherapy), each parotid mean dose should be kept as low as possible, consistent with the desired clinical target volume coverage. A lower parotid mean dose usually results in better function. Submandibular gland sparing also significantly decreases the risk of xerostomia. The currently available predictive models are imprecise, and additional study is required to identify more accurate models of xerostomia risk.

RADIATION DOSE-VOLUME EFFECTS OF OPTIC NERVES AND CHIASM

Publications relating radiation toxicity of the optic nerves and chiasm to quantitative dose and dose-volume measures were reviewed. Few studies have adequate data for dose-volume outcome modeling. The risk of toxicity increased markedly at doses >60 Gy at approximately 1.8 Gy/fraction and at >12 Gy for single-fraction radiosurgery. The evidence is strong that radiation tolerance is increased with a reduction in the dose per fraction. Models of threshold tolerance were examined.

Radiation Dose-Volume Effects In the Esophagus

Publications relating esophageal radiation toxicity to clinical variables and to quantitative dose and dose-volume measures derived from three-dimensional conformal radiotherapy for non-small-cell lung cancer are reviewed. A variety of clinical and dosimetric parameters have been associated with acute and late toxicity. Suggestions for future studies are presented.

Radiation Dose–Volume Effects and the Penile Bulb

The dose, volume, and clinical outcome data for penile bulb are reviewed for patients treated with external-beam radiotherapy. Most, but not all, studies find an association between impotence and dosimetric parameters (e.g., threshold doses) and clinical factors (e.g., age, comorbid diseases). According to the data available, it is prudent to keep the mean dose to 95% of the penile bulb volume to <50 Gy. It may also be prudent to limit the D70 and D90 to 70 Gy and 50 Gy, respectively, but coverage of the planning target volume should not be compromised. It is acknowledged that the penile bulb may not be the critical component of the erectile apparatus, but it seems to be a surrogate for yet to be determined structure(s) critical for erectile function for at least some techniques.

Local failure after complete resection of N0-1 non-small cell lung cancer

PURPOSE To estimate the risk of local-regional failure (LRF) after surgery for operable NSCLC, and the effect of clinical/pathologic factors on this risk. METHODS Records of 335 patients undergoing complete resection (lobectomy, pneumonectomy) for pathological T1-4 N0-1 NSCLC (without post-operative radiation) from 1996 to 2006 were reviewed. Crude and actuarial estimated failure rates were computed; local-regional sites included ipsilateral lung, surgical stump, hilar, mediastinal, or supraclavicular nodes. Failure times in sub-groups were calculated with the Kaplan-Meier method and compared via log-rank test. Independent factors adversely affecting LRF were determined with Cox regression. RESULTS The median follow-up duration for event-free surviving patients was 40 months (range: 1-150). The crude and actuarial 5-year probability of any failure (LR or distant) were 33% and 43%, respectively. Of all failures; 37% were LR only, 35% LR and distant and 28% distant only. The 5-year crude and actuarial probability of LRF were 24% and 35% (95% CI: 29-42%). Five-year crude LRF rates for T1-2N0, T1-2N1, T3-4N0 and T3-4N1 disease were 19% (41/216), 27% (16/59), 37.5% (15/40) and 40% (8/20), respectively. The corresponding actuarial estimates were T1-2N0 28%, T1-2N1 39%, T3-4N0 50% and T3-4N1 67%. In Cox multiple regression analysis, lymphovascular space invasion (p=0.03, HR: 1.7) and tumor size (p=0.01, HR: 1.67 for 5 cm increment) were associated with an increased risk of LRF. CONCLUSION Five-year LRF rates are ≥19% in essentially all patient subsets.

Variability in Defining T1N0 Non-Small Cell Lung Cancer Impacts Locoregional Failure and Survival

BACKGROUND Locoregional recurrence can occur despite complete anatomic resection of T1N0 non-small cell lung cancer. That may be the result of incomplete resection or inaccurate staging. We assessed the impact of extent of nodal staging on the rate of locoregional failure and patient survival. METHODS The records of 742 patients undergoing lobectomy, bilobectomy, or pneumonectomy for non-small cell lung cancer from 1996 to 2006 were reviewed. Operative reports and pathology reports were reviewed for the number of lymph nodes and the anatomic nodal stations examined. The Kaplan-Meier method was applied to analyze recurrence-free survival. RESULTS A total of 119 patients with pathologically staged Ia lung cancer were identified. Histology type included 61% (n = 73) adenocarcinoma, 27% (n = 32) squamous cell cancer, and 12% (n = 14) other. Median age was 65 years (range, 34 to 88). Mean follow-up duration was 40 months (median 47; range, 1 to 121). Locoregional recurrence occurred in 20% (n = 18). The N2 nodal stations were examined in 94% (n = 112). At least one defined N1 nodal station was examined in 70% (n = 83). Station undefined N1 nodes were examined in 27% (n = 32), and no N1 nodes were examined in 3% (n = 4). Median number of N1 lymph nodes analyzed was 5 (range, 0 to 18). The locoregional recurrence rate was 14% (12 of 83) for patients with a defined N1 station node versus 31% (11 of 36) for patients in whom there were undefined N1 nodes (p = 0.03). Similar differences were seen in disease-free survival, 78.2% versus 62.6%, respectively (p = 0.06). CONCLUSIONS Despite anatomic resection of stage Ia lung cancer and uniform analysis of N2 nodal stations, a high rate of locoregional recurrence occurs. Imprecise staging of N1 lymph nodes may contribute to the understaging and undertreatment of patients with early stage lung cancer.

Bioimaging In Vivo to Discern the Evolution of Late Effects Temporally and Spatially

tool for measuring regional radiation-induced normal tissue changes, independent of radiation volumes. Several functional imaging tools (e.g., single photon emission computed tomography [SPECT], positron emission tomography [PET], and magnetic resonance imaging [MRI]), have been used to monitor radiation-induced injury in a variety of different tissues, including the lung, heart, brain, liver, and salivary glands. the degree/extent of changes in regional imaging may be associated with changes in global organ function (e.g., clinical symptoms) at various time points.

Quantitative/Objective Analyses of RT-Induced Late Normal Tissue Injury Using Functional Imaging

There are several ways to score normal tissue injury. Imaging is an attractive tool since it allows for an objective assessment of normal tissue changes in vivo. Regional changes in tissue structure/function, detected by imaging, can be related to the different radiation doses delivered to different regions. This approach has been used for several organs, and for some, there is a clear dose–response relationship for changes in normal tissue (e.g., lung density or perfusion). Further, degree/extent of changes in regional imaging may be associated with changes in global organ function. Future improvements in imaging (e.g., more functional versus structural assessments) will afford additional opportunities for studies to better understand RT-induced normal tissue injury.