Therapeutic Ratio In Treatment Research Articles

Safety and Efficacy of Stereotactic Body Radiotherapy for Ultra-Central Thoracic Tumors

Stereotactic body radiotherapy (SBRT) is increasingly utilized in the management of ultra-central thoracic tumors, although concerns regarding significant toxicity remain. We sought to evaluate the toxicity and efficacy of SBRT to these tumors at our institution. Patients with ultra-central lung tumors or nodes treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. Ultra-central was defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus. All SBRT plans were generated with homogenous dose distributions using target coverage objectives of ITV V100% >99%, PTV V95% >99%, and an ideal PTV Dmax <105% (strict <120%). All plans were reviewed in quality assurance rounds by a team of dosimetrists, physicists, and radiation oncologists. The primary endpoint was incidence of severe toxicity (ST), defined as SBRT-related grade ≥3 toxicities, graded using the Common Terminology Criteria for Adverse Events V5.0. Secondary endpoints included local failure (LF), progression-free survival (PFS) and overall survival (OS). Competing risk analysis was used to estimate incidence and predictors of ST and LF, with death as a competing risk. Kaplan-Meier method was used to estimate PFS and OS. A total of 154 patients who received 162 ultra-central courses of SBRT were included, with a median follow-up of 21.5 months. Treatment intent was most commonly for oligoprogression (46%), oligometastasis (30%), followed by curative (20%). The most frequent tumor histologies were NSCLC (41%) and RCC (26%). SBRT prescription doses ranged from 30-55 Gy in 5 fractions (BED10 range 48-115 Gy). The most common prescription was 50 Gy in 5 fractions (42%). The cumulative incidence of ST was 8.9% at 3-years. The most common ST was pneumonitis (n = 4). Notable toxicities included bronchopleural fistula (n = 2, grade 3 and 4), bronchial stricture (n = 1, grade 3), and esophagitis leading to bleeding (n = 1, grade 4). There were no esophageal strictures or perforations, and no bronchial bleeds. There was 1 possible treatment related death from pneumonitis/pneumonia. Predictors of any ST included increased lung V5 Gy, decreased PTV V95%, and not having prior radiation therapy to the chest. The cumulative incidence of LF was 4.8%, 11% and 14% at 1-, 2-, and 3-years respectively. Predictors of LF included younger age, and greater volume of overlap between the PTV and esophagus. Median PFS was 8.4 months, while median OS was 3.7 years. In one of the largest case series of ultra-central thoracic SBRT reported to date, homogenously prescribed SBRT plans were associated with relatively low rates of ST and LF across a variety of treatment indications. Predictors of ST should be interpreted recognizing the heterogeneity in toxicities observed. Identified predictors of both ST and LF can contribute to future work to optimize the therapeutic ratio in treatment of ultra-central thoracic tumors.

Abstract P3-12-16: Five year outcomes of a prospective study of proton radiotherapy for breast cancer regional nodal irradiation

Abstract Purpose: Through improved nodal coverage and decreased dose to the heart and lung, proton therapy (PT) may improve the therapeutic ratio for treatment of breast cancer requiring regional nodal irradiation (RNI). The purpose of this study is to report 5 year disease control and toxicity. Methods: From May 2012 to February 2014, 18 women (stage IIA-IIIB) prospectively enrolled on a pilot study. Median age was 52 years (range, 42-73), with equal division between breast-conserving therapy (BCT) and mastectomy and right and left-sided cancers. Median number of positive nodes among the 16 node-positive patients was 2 (range, 1-14). Five patients had ≥ 10 nodes positive on axillary dissection (N3a). Treatment targets (CTVs for breast/chest wall, supraclavicular, axillary, internal mammary nodes (IMNs)) and organs at risk were delineated on CT scans. Double scatter PT alone was used for 10 patients (9 post-mastectomy, 1 after BCT) and combined proton-photon in 8 (all BCT). Toxicity was prospectively recorded using CTCAE v4.0. Results: Median follow-up was 4 years (range, 0.3 – 6). 5 year overall survival was 82% and locoregional control was 100%. 5 year distant metastases-free survival was 82%. No grade 4+ toxicity developed. Four patients developed grade 3 cellulitis, which was the only grade 3 toxicity. One patient had a reconstructive failure associated with a post-surgical cellulitis. A right-sided patient was diagnosed with CHF within 2 months of completion of PT, following diagnosis of a pulmonary embolus 1 month prior. She had an elevated BNP (1101) prior to PT following adriamycin-based chemotherapy. Mean heart dose was 0 Gy and cardiac V5 0%. Atrial fibrillation developed in two patients. One patient developed grade 2 pneumonitis (she received concurrent chemotherapy). One patient, with a history of rib fractures prior to PT, developed an ipsilateral rib fracture 7 months after PT. Conclusion: In a population of women with locally advanced breast cancer, PT for RNI has proven feasible after either mastectomy (with or without reconstruction) or BCT with excellent locoregional control. PT allows for highly conformal radiation delivery without compromise of target coverage or excess exposure of normal tissue. Documentation of the ultimate benefits of PT in this population, freedom from radiation induced cardiac disease and breast cancer recurrence will require prospective study of a larger numbers of patients. Citation Format: Bradley JA, Dagan R, Liang X, Ho MW, Rutenberg M, Mailhot R, Morris C, Mendenhall NP. Five year outcomes of a prospective study of proton radiotherapy for breast cancer regional nodal irradiation [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-16.

Two-year outcomes of a prospective study of proton therapy for breast cancer regional nodal irradiation.

65 Background: Through improved nodal coverage and decreased dose to the heart and lung, proton therapy (PT) may improve the therapeutic ratio for treatment of breast cancer requiring regional nodal irradiation (RNI). The purpose of this study is to report 2-year disease control and toxicity. Methods: From May 2012 to February 2014, 18 women (stage IIA-IIIB) were prospectively enrolled on a pilot study. Median age was 51.8 yrs (range, 42-73), with equal division between breast-conserving therapy (BCT) and mastectomy and right- and left-sided cancers. Median number of positive nodes among the 16 node-positive patients was 2 (range, 1-14). Five patients had ≥ 10 nodes positive on axillary dissection (N3a). Treatment targets (clinical target volumes for breast/chest wall, supraclavicular, axillary, internal mammary nodes) and organs at risk were delineated on CT scans. PT alone was used for 10 patients (9 postmastectomy; 1 postBCT) and combined proton-photon in 8 (all BCT). Toxicity was prospectively recorded using CTCAE v4.0. Results: Median follow-up was 1.9 yrs (range, 0.3 – 1.7). Two-year overall survival was 94% and locoregional control was 100%. Two-year distant metastases-free survival was 76%. No grade 4+ toxicity developed. Two patients developed grade 3 cellulitis. One patient had a reconstructive failure associated with postsurgical cellulitis. A right-sided patient was diagnosed with congestive heart failure 2 months after completing PT after diagnosis of a pulmonary embolus 1 month prior. She had elevated B-type natriuretic peptide before PT after adriamycin-based chemotherapy. Mean heart dose was 0 Gy and cardiac V5 0%. Grade 2 toxicities included pneumonitis in 1 patient who received concurrent chemotherapy, fatigue (n = 1), breast atrophy after removal of a 10x6x3cm lumpectomy cavity (n = 1), and lymphedema in 1 patient with &gt; 20 nodes surgically excised. One patient with a history of rib fractures developed an ipsilateral rib fracture 7 months after PT. Conclusions: For women with locally advanced breast cancer, PT for RNI has proven feasible after either mastectomy or BCT. PT allows for highly conformal radiation delivery without compromise of target coverage or excess exposure of normal tissue. Clinical trial information: NCT01365845.

Impact of Fraction Size on Lung Radiation Toxicity: Hypofractionation may be Beneficial in Dose Escalation of Radiotherapy for Lung Cancers

To assess how fraction size impacts lung radiation toxicity and therapeutic ratio in treatment of lung cancers. The relative damaged volume (RDV) of lung was used as the endpoint in the comparison of various fractionation schemes with the same normalized total dose (NTD) to the tumor. The RDV was computed from the biologically corrected lung dose-volume histogram (DVH), with an alpha/beta ratio of 3 and 10 for lung and tumor, respectively. Two different (linear and S-shaped) local dose-effect models that incorporated the concept of a threshold dose effect with a single parameter D(L50) (dose at 50% local dose effect) were used to convert the DVH into the RDV. The comparison was conducted using four representative DVHs at different NTD and D(L50) values. The RDV decreased with increasing dose/fraction when the NTD was larger than a critical dose (D(CR)) and increased when the NTD was less than D(CR). The D(CR) was 32-50 Gy and 58-87 Gy for a small tumor (11 cm(3)) for the linear and S-shaped local dose-effect models, respectively, when D(L50) was 20-30 Gy. The D(CR) was 66-97 Gy and 66-99 Gy, respectively, for a large tumor (266 cm(3)). Hypofractionation was preferred for small tumors and higher NTDs, and conventional fractionation was better for large tumors and lower NTDs. Hypofractionation might be beneficial for intermediate-sized tumors when NTD = 80-90 Gy, especially if the D(L50) is small (20 Gy). This computational study demonstrated that hypofractionated stereotactic body radiotherapy is a better regimen than conventional fractionation in lung cancer patients with small tumors and high doses, because it generates lower RDV when the tumor NTD is kept unchanged.

882 Poster Non-axial beams can improve therapeutic ratio in treatment of non-small cell lung cancers

882 Poster Non-axial beams can improve therapeutic ratio in treatment of non-small cell lung cancers

Definitive Radiation Management for Carcinoma of the Glottic Larynx

Radiation therapy offers excellent cure rates and preservation of the larynx in the majority of early-stage glottic cancers. Outcome may vary because of patient-, tumor-, and treatment-related variables. Carefully selected advanced lesions may also be successfully managed with irradiation. Hyperfractionation and combined chemotherapy-radiotherapy protocols seem to be promising strategies for the improvement of the therapeutic ratio in treatment of patients with more advanced lesions.