Bridging the Communication Gaps: A Prospective Single-Arm Pilot Study Testing the Feasibility of Interdisciplinary Radiotherapy Planning in Locally Advanced Lung Cancer.

RATIONALE AND OBJECTIVES: The treatment of locally advanced lung cancer (LALC) with radiotherapy (RT) can be challenging. Multidisciplinary collaboration between radiologists and radiation oncologists (ROs) may optimize RT planning, reduce uncertainty in follow-up imaging interpretation, and improve outcomes. MATERIALS AND METHODS: In this prospective clinical treatment trial (clinicaltrials.gov NCT04844736), 37 patients receiving definitive RT for LALC, six attending ROs, and three thoracic radiologists were consented and enrolled across four treatment centers. Prior to RT plan finalization, representative computed tomography (CT) slices with overlaid outlines of preliminary irradiation targets were shared with the team of radiologists. The primary endpoint was to assess feasibility of receiving feedback no later than 4 business days of RT simulation on at least 50% of plans. RESULTS: Thirty-seven patients with lung cancer were enrolled, and 35 of 37 RT plans were reviewed. Of the 35 patients reviewed, mean age was 69 years. For 27 of 37 plans (73%), feedback was received within 4 or fewer days (interquartile range 3-4 days). Thirteen of 35 cases (37%) received feedback that the delineated target potentially did not include all sites suspicious for tumor involvement. In total, changes to the RT plan were recommended for over- or undercoverage in 16 of 35 cases (46%) and implemented in all cases. Radiology review resulted in no treatment delays and substantial changes to irradiated volumes: gross tumor volume, -1.9 to +96.1%; planning target volume, -37.5 to +116.5%. CONCLUSION: Interdisciplinary collaborative RT planning using a simplified workflow was feasible, produced no treatment delays, and prompted substantial changes in RT targets.

Prospective Assessment of Patient-Reported Dry Eye Syndrome After Whole Brain Radiation.

PURPOSE: Dry eye is not typically considered a toxicity of whole brain radiation therapy (WBRT). We analyzed dry eye syndrome as part of a prospective study of patient-reported outcomes after WBRT. METHODS AND MATERIALS: Patients receiving WBRT to 25 to 40 Gy were enrolled on a study with dry mouth as the primary endpoint and dry eye syndrome as a secondary endpoint. Patients received 3-dimensional WBRT using opposed lateral fields. Per standard practice, lacrimal glands were not prospectively delineated. Patients completed the Subjective Evaluation of Symptom of Dryness (SESoD, scored 0-4, with higher scores representing worse dry eye symptoms) at baseline, immediately after WBRT (EndRT), and at 1 month (1M), 3 months, and 6 months. Patients with baseline SESoD ≥3 (moderate dry eye) were excluded. The endpoints analyzed were ≥1-point and ≥2-point increase in SESoD score at 1M. Lacrimal glands were retrospectively delineated with fused magnetic resonance imaging scans. RESULTS: One hundred patients were enrolled, 70 were eligible for analysis, and 54 were evaluable at 1M. Median bilateral lacrimal V20Gy was 79%. At 1M, 17 patients (32%) had a ≥1-point increase in SESoD score, and 13 (24%) a ≥2-point increase. Lacrimal doses appeared to be associated with an increase in SESoD score of both ≥1 point (V10Gy: P = .042, odds ratio [OR] 1.09/%; V20Gy: P = .071, OR 1.03/%) and ≥2 points (V10Gy: P = .038, OR 1.15/%; V20Gy: P = .063, OR 1.04/%). The proportion with increase in dry eye symptoms at 1M for lacrimal V20Gy ≥79% versus <79% was 46% versus 15%, respectively, for ≥1 point SESoD increase (P = .02) and 36% versus 12%, respectively, for ≥2 point SESoD increase (P = .056). CONCLUSIONS: Dry eye appears to be a relatively common, dose/volume-dependent acute toxicity of WBRT. Minimization of lacrimal gland dose may reduce this toxicity, and patients should be counseled regarding the existence of this potential side effect and treatments for dry eye.

Assessment of Risk of Xerostomia After Whole-Brain Radiation Therapy and Association With Parotid Dose.

Importance: Whole-brain radiation therapy (WBRT) delivers a substantial radiation dose to the parotid glands, but the parotid glands are not delineated for avoidance and xerostomia has never been reported as an adverse effect. Minimizing the toxic effects in patients receiving palliative treatments, such as WBRT, is crucial. Objective: To assess whether xerostomia is a toxic effect of WBRT. Design, Setting, and Participants: This observational cohort study enrolled patients from November 2, 2015, to March 20, 2018, at 1 academic center (University of North Carolina Hospitals) and 2 affiliated community hospitals (High Point Regional Hospital and University of North Carolina Rex Hospital). Adult patients (n = 100) receiving WBRT for the treatment or prophylaxis of brain metastases were enrolled. Patients who had substantial baseline xerostomia or did not complete WBRT or at least 1 postbaseline questionnaire were prospectively excluded from analysis and follow-up. Patients received 3-dimensional WBRT using opposed lateral fields covering the skull and the C1 or C2 vertebra. Per standard practice, the parotid glands were not prospectively delineated. Main Outcomes and Measures: Patients completed the University of Michigan Xerostomia Questionnaire and a 4-point bother score at baseline, immediately after WBRT, at 1 month, at 3 months, and at 6 months. The primary end point was the 1-month xerostomia score, with a hypothesized worsening score of 10 points from baseline. Results: Of the 100 patients enrolled, 73 (73%) were eligible for analysis and 55 (55%) were evaluable at 1 month. The 73 patients included 43 women (59%) and 30 men (41%) with a median (range) age of 61 (23-88) years. The median volume of parotid receiving at least 20 Gy (V20Gy) was 47%. The mean xerostomia score was 7 points at baseline and was statistically significantly higher at each assessment period, including 21 points immediately after WBRT (95% CI, 16-26; P < .001), 23 points (95% CI, 16-30; P < .001) at 1 month, 21 points (95% CI, 13-28; P < .001) at 3 months, and 14 points (95% CI, 7-21; P = .03) at 6 months. At 1 month, the xerostomia score increased by 20 points or more in 19 patients (35%). The xerostomia score at 1 month was associated with parotid dose as a continuous variable and was 35 points in patients with parotid V20Gy of 47% or greater, compared with only 9 points in patients with parotid V20Gy less than 47% (P < .001). The proportion of patients who self-reported to be bothered quite a bit or bothered very much by xerostomia at 1 month was 50% in those with parotid V20Gy of 47% or greater, compared with only 4% in those with parotid V20Gy less than 47% (P < .001). At 3 months, this difference was 50% vs 0% (P = .001). Xerostomia was not associated with medication use. Conclusions and Relevance: Clinically significant xerostomia occurred by the end of WBRT, appeared to be persistent, and appeared to be associated with parotid dose. The findings from this study suggest that the parotid glands should be delineated for avoidance to minimize these toxic effects in patients who undergo WBRT and often do not survive long enough for salivary recovery.

Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy.

CONTEXT: Salvage radiotherapy may potentially cure patients with disease recurrence after radical prostatectomy, but previous evidence has suggested that it is ineffective in patients at the highest risk of metastatic disease progression. OBJECTIVE: To delineate patients who may benefit from salvage radiotherapy for prostate cancer recurrence by identifying variables associated with a durable response. DESIGN, SETTING, AND PATIENTS: Retrospective review of a cohort of 501 patients at 5 US academic tertiary referral centers who received salvage radiotherapy between June 1987 and November 2002 for detectable and increasing prostate-specific antigen (PSA) levels after radical prostatectomy. MAIN OUTCOME MEASURE: Disease progression after salvage radiotherapy, defined as a serum PSA value > or =0.1 ng/mL above the postradiotherapy PSA nadir confirmed by a second PSA measurement that was higher than the first by any amount, by a continued increase in PSA level after treatment, or by the initiation of androgen deprivation therapy after treatment. RESULTS: Over a median follow-up of 45 months, 250 patients (50%) experienced disease progression after treatment, 49 (10%) developed distant metastases, 20 (4%) died from prostate cancer, and 21 (4%) died from other or unknown causes. The 4-year progression-free probability (PFP) was 45% (95% confidence interval [CI], 40%-50%). By multivariable analysis, predictors of progression were Gleason score of 8 to 10 (hazard ratio [HR], 2.6; 95% CI, 1.7-4.1; P<.001), preradiotherapy PSA level greater than 2.0 ng/mL (HR, 2.3; 95% CI, 1.7-3.2; P<.001), negative surgical margins (HR, 1.9; 95% CI, 1.4-2.5; P<.001), PSA doubling time (PSADT) of 10 months or less (HR, 1.7; 95% CI, 1.2-2.2; P =.001), and seminal vesicle invasion (HR, 1.4; 95% CI, 1.1-1.9; P =.02). Patients with no adverse features had a 4-year PFP of 77% (95% CI, 64%-91%). When treatment was given for early recurrence (PSA level < or =2.0 ng/mL), patients with Gleason scores of 4 to 7 and a rapid PSADT had a 4-year PFP of 64% (95% CI, 51%-76%) and of 22% (95% CI, 6%-38%) when the surgical margins were positive and negative, respectively. Patients with Gleason scores of 8 to 10, positive margins, and receiving early salvage radiotherapy had a 4-year PFP of 81% (95% CI, 57%-100%) when the PSADT was longer than 10 months and of 37% (95% CI, 16%-58%) when the PSADT was 10 months or less. CONCLUSIONS: Gleason score, preradiotherapy PSA level, surgical margins, PSADT, and seminal vesicle invasion are prognostic variables for a durable response to salvage radiotherapy. Selected patients with high-grade disease and/or a rapid PSADT who were previously thought to be destined to develop progressive metastatic disease may achieve a durable response to salvage radiotherapy.

The role of intensity modulated radiation therapy for favorable stage tumor of the nasal cavity or ethmoid sinus.

OBJECTIVES: To compare intensity-modulated radiation therapy (IMRT), 4-field conformal, and the standard 3-field conventional technique of radiotherapy for favorable stage tumors of the nasal cavity or ethmoid sinus. METHODS AND MATERIALS: We compared the 3 techniques in 3 patients with tumors of the nasal cavity or ethmoid sinus that did not involve the eye or optic pathways. We required that each plan deliver the prescription dose (70.2 Gy at 1.8 Gy per fraction) to 95% of the planning target volume. We compared the maximum point dose to critical normal structures (brainstem, optic chiasm, optic nerves, retina, lens). RESULTS: : IMRT and the 4-field conformal technique were clearly better than the 3-field conventional technique. The 4-field conformal plan was as good as IMRT. CONCLUSIONS: The conventional 3-field technique is not the best way to treat most patients with tumors between the eyes. A 4-field conformal plan is an excellent alternative to IMRT for some patients with tumors of the nasal cavity or ethmoid sinus. Conformal radiotherapy with a noncoplaner field that exits into the low neck may make it difficult to electively irradiate the neck lymphatics. IMRT may be a better option in this situation.

Contouring the middle and inner ear on radiotherapy planning scans.

The purpose of this study was to establish guidelines that help radiation oncologists contour the inner and middle ear on treatment planning scans. The radiotherapy computed tomography (CT) scans of 15 previously treated patients were reviewed for the ability to identify 3 separate auditory structures. The middle ear, the cochlea, and the vestibular apparatus were identified and contoured on each scan using anatomic landmarks. The volume and maximum axial dimension of each contour were calculated. The middle ear, cochlea, and vestibular apparatus were identified on all scans. The middle ear was defined by the tympanic membrane laterally and by the interface between air and the temporal bone in all other directions. The plane of the internal auditory canal through the temporal bone was the landmark distinguishing the vestibular apparatus from the cochlea. The mean volume of the middle ear, vestibular apparatus, and cochlea were 0.58 cm3, 0.44 cm3, and 0.14 cm3, respectively. The maximum axial dimension across the contour averaged 1.57 cm for the middle ear, 1.10 cm for the vestibular apparatus, and 0.69 cm for the cochlea. A reference atlas was constructed that shows the contour of each structure on 5 consecutive CT images. Accurate identification of the middle ear and inner ear structures on radiotherapy planning scans is possible and is necessary if critical auditory organs are to be spared during radiotherapy of targets that are located near the base of the skull. The information generated in this study will help radiation oncologists contour auditory structures accurately.

Late xerostomia after intensity-modulated radiation therapy versus conventional radiotherapy.

PURPOSE: To evaluate xerostomia following intensity-modulated radiation therapy (IMRT). MATERIALS AND METHODS: An institutional review board-approved study of xerostomia was conducted in 210 head and neck cancer patients who were beyond the acute recovery phase (> 1 year) after radiation therapy. Xerostomia was evaluated with the 8-question XQ developed and validated at the University of Michigan. RESULTS: Median XQ scores (normalized so that no xerostomia = 0 and maximum xerostomia = 100) were larynx-only group, 4 points, ipsilateral radiotherapy, 34 points; bilateral radiotherapy, 64 points; IMRT with mean contralateral parotid dose more than 26 Gy, 44 points; and IMRT with mean contralateral parotid dose 26 Gy or less, 32 points (P < 0.05 for all major comparisons). CONCLUSION: The XQ is an excellent tool for identifying important differences in xerostomia after radiation therapy for head and neck cancer. The authors' IMRT program decreases the severity of xerostomia symptoms compared with what is typically seen after conventional radiation therapy.

Postoperative adjuvant and salvage radiotherapy for prostate cancer: impact on freedom from biochemical relapse and survival.

OBJECTIVES: To determine the therapeutic outcomes in patients with high-risk prostate cancer treated with adjuvant or salvage radiotherapy (RT) after radical prostatectomy. METHODS: Between 1982 and 2000, 163 patients were treated with RT after radical prostatectomy. Adjuvant therapy was administered to 107 consecutive node-negative patients (T2-T4N0) referred to our institution less than 1 year after surgery for postoperative RT. Salvage treatment was delivered to 56 patients for a persistently elevated prostate-specific antigen level, biochemical relapse after surgery, or local recurrence. RESULTS: The median follow-up was 70 months (range 2 to 167) from the initiation of RT. Patients treated with adjuvant RT were less likely than those treated with salvage RT to experience biochemical relapse. At 5 and 10 years, the rate of freedom from biochemical relapse was 80% and 66% in the adjuvant cohort compared with 39% and 22% for patients treated with salvage intent, respectively (P <0.0001). This did not translate into a statistically significant improvement in absolute survival (72% versus 70%) or cause-specific survival (93% versus 86%) at 10 years. On multivariate analysis, neoadjuvant hormonal therapy (P = 0.0187), presence of seminal vesicle involvement (P = 0.0002), and referral indication for postoperative RT (salvage versus adjuvant RT; P <0.001) were predictors of biochemical relapse. CONCLUSIONS: In this single-institution experience, patients at high risk of disease recurrence after radical prostatectomy realized a greater biochemical relapse-free survival benefit when treated with adjuvant RT than with salvage RT. Neoadjuvant hormonal therapy and seminal vesicle involvement predicted for inferior treatment outcome.