ED visits, hospital admissions and treatment breaks in head/neck cancer patients undergoing radiotherapy.

Objectives: Radiation therapy (RT) is an integral part of treatment of head/neck cancer (HNC) but is associated with many toxicities. We sought to evaluate sociodemographic, pathologic, and clinical factors associated with emergency department (ED) visits, hospital admissions (HA), and RT breaks in HNC patients undergoing curative-intent RT. Methods: We completed a Level 3 (Oxford criteria for evidence-based medicine) analysis of a cohort of HNC patients who underwent curative-intent RT at our institution from 2013 to 2017. We collected demographic characteristics and retrospectively assessed for heavy opioid use, ED visits or HA during RT as well as RT breaks. Treatment breaks were defined as total days to RT fractions ratio ≥1.6. Multivariable stepwise logistic regression analyses were done to determine the association of various sociodemographic, pathologic, and clinical characteristics with ED visits, HA and RT treatment breaks. Results: The cohort included 376 HNC patients (294 male, 82 female, median age 61). On multivariable analysis, significant factors associated with ED visits during RT were heavy opioid use and black race. Receipt of concomitant chemotherapy was the only factor associated with hospital admissions during RT. Advanced age, lower socioeconomic class, glandular site, and receipt of chemotherapy were all independently associated with RT breaks. Lower cancer stage and lack of substance abuse history were independently associated with lack of treatment breaks. Conclusion: HNC patients with factors such as heavy opioid use, Black race, receipt of concomitant chemotherapy, and lower socioeconomic class may require closer monitoring during RT.

A Single Axial Slice of the Sternocleidomastoids and Paravertebral Muscles Associated with Worse Local Progression-Free Survival and Severe Toxicity in Sarcopenic Head and Neck Cancer Patients Undergoing Radiotherapy.

Objective The objective of this study is to contrast the predictive ability of targeted muscle groups as radiographic proxies of sarcopenia on computerized tomography (CT) with body mass index (BMI) in head and neck cancer patients (H&NCP) undergoing radiation at a safety net hospital, and to evaluate sarcopenia with survival, local progression, toxicities and treatment delays. Methods A retrospective review included 52 H&NCP treated between 2017-2019. The posterior neck muscles (PN), sternocleidomastoids (SCM), and their summed volume (AM) were contoured at C3 on patients' pre-treatment CT scans, then normalized to obtain skeletal muscle index (MI) values. Pre-treatment BMI was also evaluated. Cutoffs for sarcopenia were determined by receiver operating characteristic curves. Overall survival and local recurrence-free survival were evaluated by Kaplan-Meier. Acute grade 3 or higher toxicities were evaluated by binomial logistic regression. Results Using all neck muscles (AM-MI) produced the best model for predicting outcomes, outperforming individual muscle groups and BMI. Local progression-free survival was worse in sarcopenic patients at 25.81 months versus 35.40 months (p=0.026). Acute grade 3 or higher toxicities were associated with sarcopenia (p=0.005). Conclusions In this small, retrospective single-institution experience at a safety net hospital, a single axial slice of the combined sternocleidomastoids and paravertebral muscles at C3 performed better than either muscle group alone or pre-treatment BMI at predicting oncologic outcomes.

Knowledge-Based Planning for Robustly Optimized Intensity-Modulated Proton Therapy of Head and Neck Cancer Patients.

PURPOSE: To assess the performance of a proton-specific knowledge-based planning (KBP) model in the creation of robustly optimized intensity-modulated proton therapy (IMPT) plans for treatment of advanced head and neck (HN) cancer patients. METHODS: Seventy-three patients diagnosed with advanced HN cancer previously treated with volumetric modulated arc therapy (VMAT) were selected and replanned with robustly optimized IMPT. A proton-specific KBP model, RapidPlanPT (RPP), was generated using 53 patients (20 unilateral cases and 33 bilateral cases). The remaining 20 patients (10 unilateral and 10 bilateral cases) were used for model validation. The model was validated by comparing the target coverage and organ at risk (OAR) sparing in the RPP-generated IMPT plans with those in the expert plans. To account for the robustness of the plan, all uncertainty scenarios were included in the analysis. RESULTS: All the RPP plans generated were clinically acceptable. For unilateral cases, RPP plans had higher CTV_primary V100 (1.59% ± 1.24%) but higher homogeneity index (HI) (0.7 ± 0.73) than had the expert plans. In addition, the RPP plans had better ipsilateral cochlea Dmean (-5.76 ± 6.11 Gy), with marginal to no significant difference between RPP plans and expert plans for all other OAR dosimetric indices. For the bilateral cases, the V100 for all clinical target volumes (CTVs) was higher for the RPP plans than for the expert plans, especially the CTV_primary V100 (5.08% ± 3.02%), with no significant difference in the HI. With respect to OAR sparing, RPP plans had a lower spinal cord Dmax (-5.74 ± 5.72 Gy), lower cochlea Dmean (left, -6.05 ± 4.33 Gy; right, -4.84 ± 4.66 Gy), lower left and right parotid V20Gy (left, -6.45% ± 5.32%; right, -6.92% ± 3.45%), and a lower integral dose (-0.19 ± 0.19 Gy). However, RPP plans increased the Dmax in the body outside of CTV (body-CTV) (1.2 ± 1.43 Gy), indicating a slightly higher hotspot produced by the RPP plans. CONCLUSION: IMPT plans generated by a broad-scope RPP model have a quality that is, at minimum, comparable with, and at times superior to, that of the expert plans. The RPP plans demonstrated a greater robustness for CTV coverage and better sparing for several OARs.

Current salivary biomarkers for detection of human papilloma virus-induced oropharyngeal squamous cell carcinoma.

Human papilloma virus (HPV) infection is a key risk factor and etiology for oropharyngeal squamous cell carcinoma (OPSCC). HPV-induced OPSCC is rapidly increasing in incidence, with men experiencing increased mortality. When identified at an early stage, HPV-induced OPSCC can be successfully treated. Diagnosis of HPV-related OPSCC relies on an expert physical examination and invasive biopsy. Since saliva bathes the oropharyngeal mucosa and can be collected noninvasively, saliva obtained via salivary risings is an attractive body fluid for early detection of HPV-induced OPSCC. A plethora of DNA, RNA, and protein salivary biomarkers have been explored. This review discusses these markers and their robustness for detecting oncogenic HPV in OPSCC saliva samples. Methods detecting HPV DNA were more reliable than those detecting RNA, albeit both require time-consuming analyses. Salivary HPV proteomics are a new, promising focus of HPV detection research, and while more practical, lag behind nucleic acid detection methods in their development.

Opioid use patterns in patients with head and neck cancer receiving radiation therapy: Single-institution retrospective analysis characterizing patients who did not require opioid therapy.

BACKGROUND: We had previously analyzed the variables that determine the rates of opioid use at 1-year postradiotherapy in patients with head and neck cancer. Here we analyze the variables associated with opioid abstinence during and in the 12 months after radiotherapy at our institution. METHODS: We identified a cohort of patients with head and neck cancer who received radiotherapy as part of curative treatment at our institution. Logistic regression analyses were performed to determine socioeconomic and clinical factors associated with opioid abstinence. RESULTS: The cohort included 376 patients. On multivariable analysis, patients from an upper-income class (p = 0.004), black race (p = 0.004), older (p = 0.008), with dependent children (p < 0.001) or receiving surgery (p = 0.002) were more likely to abstain from opioids, while patients using analgesic mouthwash (p = 0.009) or higher pain scale (p = 0.002) were less likely. CONCLUSION: Socioeconomic and treatment characteristics are associated with opioid abstinence during and following radiation treatment in patients with head and neck cancer.

MRI-guided stereotactic ablative radiation therapy of spinal bone metastases: a preliminary experience.

OBJECTIVE: MRI provides clear visualization of spinal cord, tumor, and bone for patient positioning and verification during MRI-guided radiotherapy (MRI-RT). Therefore, we wished to evaluate spine stereotactic ablative radiotherapy (SABR) feasibility with MRI-RT. Given dosimetric limitations of first generation Co-60 MRI-RT, we then evaluated improvements by newer linear accelerator (linac) MRI-RT. METHODS: Nine spinal metastases were treated with Co-60 MRI-RT. Seven received a single 16 Gy fraction, and two received three fractions totaling 24 or 30 Gy. After replanning with linac MRI-RT software, comparisons of organ at risk and dose spillage objectives between Co-60 and linac plans were performed. RESULTS: Spinal cord and cauda equina dose constraints were met in all Co-60 cases. Treatments were delivered successfully with real-time imaging during treatment and no treatment-related toxicities. While limits for dose spillage into surrounding soft tissues were not achieved due to the limitations of the Co-60 system, this could be corrected with linac MRI-RT delivery. CONCLUSIONS: MRI-RT SABR of spinal metastases is feasible with Co-60 MRI-RT. Dose delivery is improved by linac MRI-RT. ADVANCES IN KNOWLEDGE: This is the first report of MRI-RT for SABR of spinal metastases. The enhanced visualization of anatomy by MRI may facilitate RT dose escalation for spine SABR.

Long-term opioid use in curative-intent radiotherapy: One-Year outcomes in head/neck cancer patients.

BACKGROUND: No study has determined the incidence of long-term opioid use, or risk factors for long-term use, ≥1 year after radiotherapy. METHODS: Medical records of 276 head/neck cancer patients were retrospectively assessed for persistent opioid use 1-year after curative-intent radiotherapy. Numerous potential risk factors were assessed and the physicians' documented reasons for continued use were qualitatively categorized as suspected opioid use disorder (OUD) or as medically indicated for control of ongoing pain. RESULTS: Of note, 20 of 276 patients continued using opioids long-term. High maximum opioid dose and the use of opioids and/or psychotropics/non-opioid analgesics at the radiation oncology intake visit were associated with this outcome. Three patients continued due to suspected OUD and 17 due to medical indications. CONCLUSION: Of note, 7.2% of patients developed long-term opioid use, which was associated with high maximum opioid dose and early initiation of opioids and/or psychotropics/non-opioid analgesics. Physicians cited medical indications as the primary reason for continued use.

Dosimetric comparison of intensity-modulated radiation therapy for early-stage glottic cancers with and without the air cavity in the planning target volume.

For early-stage glottic cancers, intensity-modulated radiation therapy (IMRT) has been shown to have comparable local control to 3D-conformal radiotherapy with the advantage of decreased dose to the carotid arteries. The planning target volume (PTV) for early glottic cancers typically includes the entire larynx, plus a 3 to 5 mm uniform margin. The air cavity within the larynx creates a challenge for the inverse optimization process as the software attempts to "build up" dose within the air. This unnecessary attempt at dose build-up in air can lead to hot spots within the rest of the PTV and surrounding soft tissue. We hypothesized that removal of the air from the PTV would decrease hot spots and allow for a more homogeneous plan while still maintaining adequate coverage of the PTV. We analyzed 20 consecutive patients with early-stage glottic cancer, T1-2N0, who received IMRT at our institution from April 2015 to December 2016. Each patient received 63 to 65.25 Gy in 2.25 Gy per fraction. Two plans were created for each case: one in which the PTV included the laryngeal air cavity and one in which the air cavity was subtracted from the PTV to create a new PTV-air structure. Dosimetric variables were collected for PTV-air structure from both IMRT plans, including V100%, D98% D2%, and D0.2%. Dosimetric variables for spinal cord and the carotid arteries were also recorded. Homogeneity index (HI) defined as D98/D2 was calculated. Two-sided t-tests were used to compare dosimetric variables. The median PTV volume was 69.9 cc (standard deviation [SD] ± 28.7 cc) and the median air cavity volume removed was 11.0 cc (SD ± 3.4 cc). A 2-sided t-test revealed a statistically significant decrease in max dose (112.7% vs 108.8%, p value = 0.0002) and improvement of HI (0.93 vs 0.91, p value = 0.0023) for the PTV air in the IMRT plan optimized for PTV air, which had air excluded, compared to the IMRT plan optimized for PTV with air included. There was no significant worsening of PTV-air coverage or significant increase in doses to the organs at risk (OARs). The removal of the air cavity from the PTV for early-stage glottic cancers does not compromise PTV coverage or sparing of OARs and can result in a more homogeneous IMRT plan. A more homogeneous plan has the potential to reduce treatment morbidity, although further study is warranted to investigate the clinical impact of air cavity removal from the PTV.

Disparities in adherence to head and neck cancer follow-up guidelines.

OBJECTIVES: In this study, we aim to determine the frequency of adherence to National Comprehensive Cancer Network follow-up guidelines in a population of head and neck cancer patients who received curative treatment. We will also assess the impact of race, ethnicity, socioeconomic status, and treatment setting on utilization of follow-up care. METHODS: This study included patients with biopsy-proven, nonmetastatic oropharyngeal or laryngeal cancer treated with radiotherapy between January 1, 2014, and June 30, 2016, at a safety-net hospital or adjacent private academic hospital. Components of follow-up care analyzed included an appointment with a surgeon or radiation oncologist within 3 months and posttreatment imaging of the primary site within 6 months. Univariable and multivariable analyses were conducted using a logistic regression model to estimate odds ratios and corresponding 95% confidence intervals. RESULTS: Two hundred and thirty-four patients were included in this study. Of those, 88.8% received posttreatment imaging of the primary site within 6 months; 88.5% attended a follow-up appointment with a radiation oncologist within 3 months; and 71.1% of patients attended a follow-up appointment with a surgeon within 3 months. On multivariable analysis, private academic hospital treatment versus safety-net hospital treatment was associated with increased utilization of both surgical and radiation oncology follow-up. Non-Hispanic black (NHB) patients, Hispanic patients, and those with a low socioeconomic status were also less likely to receive follow-up. CONCLUSION: Safety-net hospital treatment, socioeconomic status, Hispanic ethnicity, and NHB race were associated with decreased follow-up service utilization. Quality improvement initiatives are needed to reduce these disparities. LEVEL OF EVIDENCE: 2b Laryngoscope, 129:2303-2308, 2019.

Feasibility of Adaptive MR-guided Stereotactic Body Radiotherapy (SBRT) of Lung Tumors.

Online adaptive radiotherapy (ART) with frequent imaging has the potential to improve dosimetric accuracy by accounting for anatomical and functional changes during the course of radiotherapy. Presented are three interesting cases that provide an assessment of online adaptive magnetic resonance-guided radiotherapy (MRgRT) for lung stereotactic body radiotherapy (SBRT). The study includes three lung SBRT cases, treated on an MRgRT system where MR images were acquired for planning and prior to each treatment fraction. Prescription dose ranged from 48 to 50 Gy in four to five fractions, normalized to where 95% of the planning target volume (PTV) was covered by 100% of the prescription dose. The process begins with the gross tumor volume (GTV), PTV, spinal cord, lungs, heart, and esophagus being delineated on the planning MRI. The treatment plan was then generated using a step-and-shoot intensity modulated radiotherapy (IMRT) technique, which utilized a Monte Carlo dose calculation. Next, the target and organs at risk (OAR) contours from the planning MRI were deformably propagated to the daily setup MRIs. These deformed contours were reviewed and modified by the physician. To determine the efficacy of ART, two different strategies were explored: 1) Calculating the plan created for the planning MR on each fraction setup MR dataset (Non-Adapt) and 2) creating a new optimized IMRT plan on the fraction setup MR dataset (FxAdapt). The treatment plans from both strategies were compared using the clinical dose-volume constraints. PTV coverage constraints were not met for 33% Non-Adapt fractions; all FxAdapt fractions met this constraint. Eighty-eight percent of all OAR constraints studied were better on FxAdapt plans, while 12% of OAR constraints were superior on Non-Adapt fractions. The OAR that garnered the largest benefit would be the uninvolved lung, with superior sparing in 92% of the FxAdapt studied. Similar, but less pronounced, benefits from adaptive planning were experienced for the spinal cord, chest wall, and esophagus. Online adaptive MR-guided lung SBRT can provide better target conformality and homogeneity and OAR sparing compared with non-adaptive SBRT in selected cases. Conversely, if the PTV isn't adjacent to multiple OARs, then the benefit from ART may be limited. Further studies, which incorporate a larger cohort of patients with uniform prescriptions, are needed to thoroughly evaluate the benefits of daily online ART during MRgRT.

Assessment of Oropharyngeal and Laryngeal Cancer Treatment Delay in a Private and Safety Net Hospital System.

Objective To examine the impact of treatment setting and demographic factors on oropharyngeal and laryngeal cancer time to treatment initiation (TTI). Study Design Retrospective case series. Setting Safety net hospital and adjacent private academic hospital. Subjects and Methods Demographic, staging, and treatment details were retrospectively collected for 239 patients treated from January 1, 2014, to June 30, 2016. TTI was defined as days between diagnostic biopsy and initiation of curative treatment (defined as first day of radiotherapy [RT], surgery, or chemotherapy). Results On multivariable analysis, safety net hospital treatment (vs private academic hospital treatment), initial diagnosis at outside hospital, and oropharyngeal cancer (vs laryngeal cancer) were all associated with increased TTI. Surgical treatment, severe comorbidity, and both N1 and N2 status were associated with decreased TTI. Conclusion Safety net hospital treatment was associated with increased TTI. No differences in TTI were found when language spoken and socioeconomic status were examined in the overall cohort.

Transoral robotic surgery for oropharyngeal squamous cell carcinoma in the era of human papillomavirus.

BACKGROUND: The emergence of transoral robotic surgery (TORS) ignited the debate between surgical and nonsurgical strategies on oropharyngeal squamous cell carcinoma (SCC) management; a question further complicated by human papillomavirus (HPV). We evaluated the survival by treatment strategy independently in HPV-related and HPV-nonrelated oropharyngeal SCC. METHODS: The National Cancer Database was queried for patients with oropharyngeal SCC with known HPV status who underwent primary TORS or primary radiotherapy. The overall survival (OS) was compared by treatment strategy, including propensity matching to control for confounders. RESULTS: Of 1873 patients, 73% were HPV-positive and 30% were treated with TORS. The propensity-matched patients with HPV-positive disease displayed no significant difference in 3-year survival; 95% versus 91% (P = .116) for the TORS versus primary radiotherapy. In the HPV-negative cohort, TORS was associated with superior survival; 84% versus 66% (P = .01). CONCLUSION: The TORS-based approach was associated with superior survival in patients with HPV-negative oropharyngeal SCC; similar difference was not observed in patients with HPV-positive disease.

Nutrition and Swallowing Therapy in Head and Neck Cancer: Utilization of Care and Preventative Efficacy.

PURPOSE: To examine the impact of ethnicity, Spanish language preference, socioeconomic status, and treatment setting on utilization of supportive services before radiotherapy (RT) among head and neck cancer patients and to determine whether a lack of these services is associated with an increased rate of adverse events. METHODS AND MATERIALS: Demographic, staging, and treatment details were retrospectively collected for patients treated at a safety-net hospital (n = 56) or adjacent private academic hospital (n = 183) from January 1, 2014, to June 30, 2016. Supportive care services evaluated were limited to speech/swallowing therapy and nutrition therapy. Adverse events and performance measures examined included weight loss during RT, gastric tube placement, emergency department visits, hospital admissions, and missed RT days. RESULTS: On multivariable analysis, patients receiving treatment at the safety-net hospital were less likely to receive speech/swallowing services. Receiving speech/swallowing therapy before treatment was associated with less weight loss during treatment, and in conjunction with nutrition therapy, was associated with fewer missed RT days. CONCLUSION: Safety-net hospital treatment was associated with a lack of utilization of pre-RT speech/swallowing therapy which in turn was associated with increased weight loss. Interventions aimed at improving utilization of these services would improve treatment tolerance and patient outcomes.

Adjuvant therapies utilization pattern and survival outcomes in high-grade head and neck soft tissue sarcoma; a population based study.

PURPOSE: Head and neck soft tissue sarcoma (HNSTS) is a distinct entity within the soft tissue sarcoma group and the evidence supporting treatment options for this disease is poorly defined. Using the National Cancer Database, this study aims to reveal adjuvant therapy utilization patterns and their outcomes. MATERIALS: HNSTS patients constituted 6.5% of all sarcoma patients and the analysis was limited to non-metastatic patients who underwent resection between 2004 and 2012. Chi-square test assessed the distribution of demographic, tumor and treatment variables in the treatment subgroups. Kaplan-Meier method estimated overall survival and proportional hazards model estimated survival hazard ratios for prognostic factors including age, comorbidity, gender, race, size, grade, margin status, histology, chemotherapy administration and radiotherapy technique/dose. RESULTS: The cohort included 2493 patients with a median age of 62years. Adjuvant therapies were more frequently delivered in high-grade, large tumors and with positive surgical margins. Limiting the analysis to 788 high-grade HNSTS patients, adjunctive radiotherapy improved 5-year survival from 44% (95% confidence interval (CI): 38-50) to 49% (CI: 43-55); reducing mortality hazards ratio by 24% (p<0.001). On multivariate analysis, older age, positive surgical margins and large tumor size were significant predictors of poor survival. These findings were consistent after propensity score analysis. CONCLUSION: Our analysis suggests that adjuvant radiotherapy is associated with improved survival in high-grade HNSTS. Higher dose and precise technique did not accentuate this benefit; however, further studies are needed to refine the treatment strategies, including the role of chemotherapy in the management of this rare disease.

Intensity-modulated radiotherapy for early glottic cancer: transition to a new standard of care?

For decades, the standard of care for radiation treatment of early larynx cancers has been conventional treatment using opposed lateral fields encompassing the larynx and overlying neck structures, including the adjacent carotid arteries. While intensity-modulated radiotherapy (IMRT) has replaced conventional radiotherapy for all other head/neck cancer situations, the use of IMRT to treat early glottic cancers remains controversial. The article reviews the published experience with IMRT for this clinical situation and provides a detailed review of the literature on radiation-induced carotid toxicity and how it might apply to the controversy. Finally, we discuss whether the radiation oncology community should transition to IMRT as a new standard of care for the treatment of early glottic cancers.

Intrathoracic extensive-stage small cell lung cancer: assessment of the benefit of thoracic and brain radiotherapy using the SEER database.

BACKGROUND: Extensive-stage small cell lung cancer (ESCLC) includes metastatic disease and locally advanced disease confined to the thorax that cannot be encompassed in a typical radiation portal. We assessed and then compared the benefits of thoracic radiotherapy (TRT) and/or brain radiotherapy (BRT) on overall survival (OS) between the intrathoracic (T-ESCLC) and metastatic (M-ESCLC) groups using the Surveillance Epidemiology and End Results database. METHODS: TRT and BRT data were available for 10150 patients treated from 1988-1997. The T-ESCLC group included 1774 patients. The Kaplan-Meier method was used to estimate OS and the proportional hazards model was used to estimate OS hazard ratios for prognostic factors including age, gender, race, tumor size, T/N stage, TRT, and BRT. RESULTS: The 2-year OS for T-ESCLC was 7.8 % compared to 3 % in the M-ESCLC group (p < 0.001). In the T-ESCLC group, TRT and BRT were delivered to 750 and 102 patients, respectively. The 2-year OS was 13 % in the TRT group compared to 4.1 % in the no-TRT group (p ≤ 0.001) and 22.5 % in the BRT group compared to 7 % in the no-BRT group (p < 0.001). In the M-ESCLC group, TRT and BRT were delivered to 3093 and 1887 patients, respectively. The 2-year OS was 4.4 % in the TRT group compared to 2.8 % in the no-TRT group (p < 0.001) and 4.3 % in the BRT compared to 2.6 % in the no-BRT group (p < 0.001). Age, gender, TRT and BRT were significant OS prognostic factors in both groups. CONCLUSIONS: Our study suggests that T-ESCLC is a disease entity distinct from M-ESCLC. Prospective studies to determine whether TRT should be recommended for the thoracic-only subgroup are warranted.

Stereotactic body radiotherapy in patients with stage I non-small-cell lung cancer aged 75 years and older: retrospective results from a multicenter consortium.

BACKGROUND: This study was a retrospective analysis of elderly patients treated with stereotactic body radiotherapy (SBRT) in the setting of a multi-institutional consortium. PATIENTS AND METHODS: Three institutions pooled data on patients aged ≥ 75 years who received SBRT for stage I non-small-cell lung cancer (NSCLC). Forty-seven tumors in 46 patients were analyzed in patients aged 75 to 92 years (median, 82 years). Treatment was delivered during 2007 to 2009, with a median follow-up of 12.4 months. All patients underwent staging positron emission tomography-computed tomography (PET-CT), and 87% of tumors were confirmed by biopsy results. Total doses were 35 to 60 Gy, mainly in 3 to 5 fractions. All tumors were treated using a linear accelerator, with 96% of patients receiving 3-dimensional (3D) conformal RT and 4% undergoing intensity modulated RT (IMRT). RESULTS: At the time of analysis, the local failure rate was 2% (1 of 47). The regional failure rate was 9% (4 of 47). The distant failure rate was 6% (3 of 47). The combined failure rate was 15% (7 of 47) because 1 patient experienced both regional and distant failure. Among 20 tumors with any acute toxicity, there were no ≥ grade 3 toxicities. Pneumonitis (n = 10) grades 1 (n = 3) and 2 (n = 2) was seen in 15% and 10% of patients, respectively; these data were missing for 25% of patients. CONCLUSION: SBRT in patients aged ≥ 75 years with stage I NSCLC proved tolerable, with toxicity rates comparable to those in younger patients. Excellent rates of local, regional, and distant control were achieved at a median follow-up of 12.4 months. This patient population represents a rapidly growing segment of the early lung cancer population, and SBRT appears to be a safe and effective treatment option for patients who are not optimal candidates for surgery.

Id1 delays senescence of primary human melanocytes.

The Id family of helix-loop-helix transcription factors is upregulated in a variety of human malignancies and has been implicated in promoting tumorigenesis through effects on cell growth, differentiation, and tumor angiogenesis. While expression of Id proteins has been associated with tumorigenesis, the precise mechanistic relationship between Id expression and carcinogenesis has not been clearly delineated. We have previously shown that Id1 delays cellular senescence in primary mammalian cells through inhibition of the cell cycle regulatory protein and familial melanoma gene, p16/INK4a. We have also demonstrated that Id1 expression is upregulated in early stage primary human melanomas and may be an important marker for early malignancy. In order to further define the role of Id1 in human melanoma development, we have evaluated the function of Id1 in primary human melanocytes. Here we show that constitutive expression of Id1 in primary human melanocytes leads to delayed cellular senescence and decreased expression of the familial melanoma gene, p16/INK4a. Although melanocytes constitutively expressing Id1 are shown to possess extended lifespans, this is not associated with an appreciable change in cell growth or telomere length. We conclude that Id1 delays cellular senescence in primary human melanocytes through inhibition of p16/INK4a expression and suggest that Id1 may contribute to the malignant conversion of primary human melanocytes through extension of cellular lifespan.