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Ben Slotman
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ES04 - Multimodality Management of Small Cell and Neuroendocrine Cancers (ID 7)
- Event: WCLC 2019
- Type: Educational Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 6
- Now Available
- Moderators:Enric Carcereny, Ben Slotman
- Coordinates: 9/08/2019, 10:30 - 12:00, Toronto (1985)
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ES04.01 - Update in Systemic Treatment of SCLC (Now Available) (ID 3168)
10:30 - 12:00 | Presenting Author(s): Sumitra Thongprasert
- Abstract
- Presentation
Abstract
Chemotherapy combination of cisplatin plus etoposide is the standard option for extensive stage Small Cell Lung Cancer (SCLC); though the response rate was very high, however most cases of the extensive stage recurred within one year and there was no good regimen for second line. Several chemotherapeutic agents such as topotecan, irinotecan, amrubicin or combination of cyclophosphamide, doxorubicin and vincristine (CAV) had been used as second line treatment with minimal benefit.
Within the past couple years there’re the new way of treating lung cancer especially the use of immunotherapy, which several agents had their roles in the treatment of Non-Small Cell Lung Cancer (NSCLC). The study of immunotherapy in SCLC was very slow. The use of T cell immune-checkpoint inhibitors (anti-PD1: nivolumab, pembrolizumab; anti-PD-L1: atezolizumab, durvalumab; anti-CTLA-4: ipilimumab, tremelimumab) have shown promising antitumor activity with the potential to prolong survival in SCLC patients.
Nivolumab was the first immunotherapy agent that had approved by The US Food and Drug Administration (FDA) 2018 to be the third line drug according to the outcome in CheckMate-032, which’s a multicenter, open-label trial in patients with metastatic solid tumors. This subgroup comprised 109 patients with metastatic SCLC, with disease progression after platinum-based therapy and at least one other prior line of therapy, regardless of tumor PD-L1 status. All patients received nivolumab at3 mg/kg by intravenous infusion over 60 minutes every 2 weeks. The ORR was 12% (95% CI: 6.5, 19.5). Responses were durable for 6 months or longer in 77%, 12 months or longer in 62%, and 18 months or longer in 39% of the 13 responding patients. PD-L1 tumor status did not appear to be predictive of response.
Pembrolizumab has been granted a priority review designation by the FDA for the treatment of patients with advanced small cell lung cancer (SCLC) whose disease has progressed following ≥2 prior lines of therapy. Data from the phase II KEYNOTE-158 and phase Ib KEYNOTE-028 studies, pembrolizumab at 200 mg intravenously (IV) every 3 weeks for 2 years or until disease progression, unacceptable toxicity, or study withdrawal elicited 19% and 33% overall response rates (ORRs) in patients with extensive-stage SCLC, respectively.
Atezolizumab plus carboplatin and etoposide, was approved by FDA for the first-line treatment of adult patients with extensive-stage small cell lung cancer based on the data from IMpower133 which is a randomized treatment using atezolizumab 1200 mg and carboplatin AUC 5 mg/mL/min on day 1 and etoposide 100 mg/m2 intravenously on days 1, 2 and 3 of each 21-day cycle for a maximum of 4 cycles, followed by atezolizumab 1200 mg once every 3 weeks until disease progression or unacceptable toxicity, or placebo and carboplatin AUC 5 mg/mL/min on day 1 and etoposide 100 mg/m2 intravenously on days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles, followed by placebo once every 3 weeks until disease progression or unacceptable toxicity. Overall survival (OS) was 12.3 months for patients receiving atezolizumab with chemotherapy and 10.3 months for those receiving placebo with chemotherapy (hazard ratio 0.70; 95% CI: 0.54, 0.91; p=0.0069). Median PFS was 5.2 months (4.4, 5.6) compared with 4.3 months (4.2, 4.5) in the atezolizumab and placebo arms, respectively (HR 0.77; 0.62, 0.96; p=0.0170).
In conclusion, there are several new ways and also new agents that target the immune cell and should be able to improve the outcome and survival of SCLC.
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ES04.02 - Pathology Overview for Carcinoid and NE Spectrum (Now Available) (ID 3169)
10:30 - 12:00 | Presenting Author(s): Elisabeth Brambilla
- Abstract
- Presentation
Abstract
Pathology Overview for carcinoid and Neuroendocrine Spectrum
The spectrum of neuroendocrine (NE) tumors ranges from low grade typical carcinoid (TC) to intermediate grade Atypical carcinoids to high grade small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) Although very different from high grade tumors in their molecular genetics and expression profiling, carcinoid are included in the spectrum of NE tumors since WHO 2015 (1) on the basis of their common NE epithelial differentiation.Carcinoids display many clinical differences with high grade NE tumors being not strongly associated with smoking (only 20-40% smokers), their specific association with Multiple Endocrine Neoplasia type 1 (MEN1 ) not seen in High grade tumors and their occurrence on the background of NE cell hyperplasia and tumorlets in 60% of TC and AC, very rare in high grade tumors . Whereas carcinoid are never combined with conventional lung cancer , 20 to 25% of SCLC and LCNEC are combined. Since the NE markers are common in the full spectrum , morphology , mitoses and KI 67 (proliferations markers) are useful to differentiate carcinoids from SCLC and LCNEC . The accurate diagnosis of each is critical in view of their eminently different therapeutic management .
Small cell lung carcinoma (SCLC
SCLC is the most frequent NE lung tumor (15-20% of lung cancer) and has the worse prognosis in the spectrum. Most are proximal,70% perihilar forming peribronchial growth involving lymph nodes .Less than 5% are solitary primary nodules stage I. SCLC is a high grade malignant epithelial NE tumor with characteristic cytopathologic features recognizable in routine microscopy without use of immunohistochemistry (IHC) in optimal cell preservation. IHC may be used in suboptimal condition (crush artifact) to confirm the diagnosis.
SCLC is made of sheets of small cells ,round/oval or spindle shaped forming whorls, with little cytoplasm , nuclei with unconspicuous nucleoli , finely granular dispersed chromatin , and nuclear molding . Mitotic rate is very high more than 50 reaching 100 for 2mm2 and KI67 exceeds 50% (50-100%).Extensive necrosis is frequent .Most SCLC express NE markers Chromogranine A, Synaptophysin and CD56 . 75% express TTF1 (recommended clone 8G7G3 1) . Less than 10% remain negative for all 3 NE markers and TTF1 . In these cases a P40 staining is mandatory to eliminate a basaloid carcinoma (P40 Positive) with which it may be confused in suboptimal preparations .
SCLC can present as pure or combined. Any association of small cells with another NSCLC (Adenocarcinoma, Squamous cell carcinoma , large cell or large cell NE carcinoma , sarcomatoid giant and spindle cells ) is diagnosed as combined SCLC (20%) .
Several studies of their molecular characteristics were recently published and compared with other tumors of the NE spectrum . Theses are specific , closer from a part of LCNEC but distinct from theses of carcinoids (Georges 2016 , Georges 2018 ) . Small cell carcinoma in non-smokers should be looked for EGFR mutation (acquired after TKI therapy of an Adenocarcinoma or spontaneous ).
Large cell neuro endocrine carcinoma (LCNEC)
LCNEC is a high grade NE lung tumor accounting for 3% of lung cancers .The diagnosis is based on the necessary association of NE morphology (organoid nesting ,rosettes ,palisading) and expression of NE markers (at least one) : chromogranine A, synaptophysin and CD56. Seventy-nine % develop in the lung periphery , 5% show endobronchial growth .They form circonscribed nodular mass intensely necrotic .They lack typical cytology in contrast with SCLC .The mitotic rate is more than 10 per 2mm2to distinguish them from atypical carcinoid (2 -10/2mm 2) ,ranging from 20 to 80-100 with KI67 very high exceeding 50% usually 80-100%. They are composed of large cells with low nuclear to cytoplasmic ratio , a conspicuous nucleoli and vesicular chromatin .A spectrum of morphologies range from SCLC (small cell –like) to non small cell-like or to a few atypical carcinoids-like , showing the need for an accurate diagnosis using objective criteria (proliferation). A constellation of multiple criteria should be used to distinguish them fro SCLC or AC .Combined LCNEC is the association of any LCNEC component with a conventional component ( 25% ). Due to spatial heterogeneity of NE morphology and NE expression the diagnostic may be difficult on small biopsies .However a NSCLC without NE morphology but 1 or 2 NE markers is diagnosed as a NSCLC (with unclear phenotype ) since 15 % of NSCLC also express 1 or 2 NE markers.TTF1 is expressed in 41 % of LCNEC specially when combined with adenocarcinoma.Molecular genomics and expression profiling classify in 2 categories one simiilar to SCLC with biallelic inactivation of P53 and RB genes and another with KEAP 1 or LKB1 mutations looking like NSCLC .LCNEC are very different from Carcinoids (Georges 2018 )
Carcinoids tumors : Typical and Atypical Carcinoids
Carcinoids account for 1-2 % of lung tumors of which 10% are Atypical carcinoid .Typical ( low grade) and atypical carcinoids(intermediate grade) are distinquished on objective criteria (mitoses index (table I) and necrosis, but KI67 has no defined cut- off to separate them.
They develop centrally as endobronchial growth or in the lung periphery (16-40 %) Cytology allows accurate recognition . NE morphology is well achieved with organoid patterns( glandular, follicular ,trabecular , angiomatoid…) most often multiple .Spindle cell pattern is more frequent in the peripheral carcinoids.
All express the 3 NE markers and TTF1 is usually negative (except in a few peripheral carcinoids )
References
Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. WHO classification of tumours of the lung, pleura, thymus and heart, 4th ed. Lyon: IARC; 2015.
Travis WD ,Nicholson AG ,Geisinger KR, Brambilla E.Tumors of the lower respiratory tract AFIP Atlas of Tumor pathology series 4 ed. AFIP Press Bethesda 2019
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ES04.03 - Surgery for Early and Locally Advanced Small Cell Lung Cancer (Now Available) (ID 3170)
10:30 - 12:00 | Presenting Author(s): Eric Lim
- Abstract
- Presentation
Abstract not provided
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ES04.04 - Role of Stereotactic Body Radiation in Early and Advanced SCLC (Now Available) (ID 3171)
10:30 - 12:00 | Presenting Author(s): Roy Decker
- Abstract
- Presentation
Abstract
Stereotactic Body Radiotherapy (SBRT) has been rapidly adopted as the standard of care for patients with early-stage Non-Small Cell Lung Cancer (NSCLC) who are medically inoperable, and more recently for selected patients with oligometastatic cancer. The utilization of SBRT in patients with Small Cell Lung Cancer (SCLC) is markedly lower, reflecting both the lower incidence and the lack of clinical data, but it has been increasing over the past several years. Given the aggressive nature and high metastatic potential of SCLC, the optimal integration of SBRT into the multimodality treatment of early-stage SCLC patients is critical, so that we don’t delay or otherwise compromise systemic therapy. In patients with advanced or recurrent SCLC, SBRT offers a valuable treatment option for well selected patients, a group that may be increasing as new therapeutic options emerge.
Small Cell Lung Cancer (SCLC) represents less than 20% of all new lung cancer diagnoses. Compared to NSCLC, SCLC is less likely to present with localized disease, carries a higher risk of metastatic failure, and stage for stage is associated with worse overall survival. The majority of limited stage SCLC patients have locally advanced tumors, and the standard of care remains concurrent chemotherapy with fractionated thoracic radiation. Stage I SCLC is diagnosed in less than 5% of incident cases. Given the propensity for nodal metastasis, invasive staging of the mediastinum is indicated in all of these patients. For those who are node negative, there is a limited amount of data to guide decisions about optimal management. Surgery has emerged as a standard of care for operable patients, based on favorable outcomes in population-based studies. Following surgery, adjuvant chemotherapy is recommended regardless of tumor size, based on the high risk of subsequent metastatic failure.
For those patients who won’t tolerate lobectomy, consensus guidelines now recognize that Stereotactic Body Radiotherapy (SBRT) is a treatment option, and a reasonable alternative to conventional chemoradiotherapy. This is largely justified by the observed increased efficacy of SBRT compared to fractionated radiation in stage I NSCLC, an observation which is now supported by a randomized trial. The published data to date suggests that the utilization of SBRT in stage I SCLC has been increasing. Single- and multi-institutional case series suggest, unsurprisingly, that this approach appears to be safe, and the efficacy in terms of local control appears to be similar to that seen in NSCLC patients. In the US, the use of SBRT in SCLC appears to be more common in elderly patients, and the utilization seems to be driven by large institutions.
Chemotherapy is an essential part of multimodality care of SCLC in all stages of disease. The addition of adjuvant chemotherapy sequentially after SBRT in early stage patients is associated with improved survival in retrospective studies, similar to the better outcomes seen with surgery and chemotherapy in operable SCLC patients. Recent and ongoing prospective efforts are evaluating concurrent chemotherapy with SBRT, including both traditional short-course and more extended hypo-fractionated radiation schedules.
Trends in stereotactic body radiation therapy for stage I small cell lung cancer. Stahl JM, Corso CD, Verma V, Park HS, Nath SK, Husain ZA, Simone CB 2nd, Kim AW, Decker RH. Lung Cancer. 2017 Jan;103:11-16.
Multi-Institutional Experience of Stereotactic Ablative Radiation Therapy for Stage I Small Cell Lung Cancer. Verma V, Simone CB 2nd, Allen PK, Gajjar SR, Shah C, Zhen W, Harkenrider MM, Hallemeier CL, Jabbour SK, Matthiesen CL, Braunstein SE, Lee P, Dilling TJ, Allen BG, Nichols EM, Attia A, Zeng J, Biswas T, Paximadis P, Wang F, Walker JM, Stahl JM, Daly ME, Decker RH, Hales RK, Willers H, Videtic GM, Mehta MP, Lin SH. Int J Radiat Oncol Biol Phys. 2017 Feb 1;97(2):362-371.
Clinical Outcomes of Stereotactic Body Radiotherapy for Patients With Stage I Small-Cell Lung Cancer: Analysis of a Subset of the Japanese Radiological Society Multi-Institutional SBRT Study Group Database. Shioyama Y, Onishi H, Takayama K, Matsuo Y, Takeda A, Yamashita H, Miyakawa A, Murakami N, Aoki M, Matsushita H, Matsumoto Y, Shibamoto Y; Japanese Radiological Society Multi-Institutional SBRT Study Group (JRS-SBRTSG). Technol Cancer Res Treat. 2018 Jan 1;17:1533033818783904.
Stereotactic body radiotherapy with concurrent chemotherapy extends survival of patients with limited stage small cell lung cancer: a single-center prospective phase II study. Li C, Xiong Y, Zhou Z, Peng Y, Huang H, Xu M, Kang H, Peng B, Wang D, Yang X. Med Oncol. 2014 Dec;31(12):369.
Outcomes of Stereotactic Body Radiotherapy for T1-T2N0 Small Cell Carcinoma According to Addition of Chemotherapy and Prophylactic Cranial Irradiation: A Multicenter Analysis. Verma V, Simone CB 2nd, Allen PK, Lin SH. Clin Lung Cancer. 2017 Nov;18(6):675-681.e1.
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ES04.05 - Advances in Radionuclide Treatment for Neuroendocrine Tumours (Now Available) (ID 3172)
10:30 - 12:00 | Presenting Author(s): Angela Lamarca
- Abstract
- Presentation
Abstract
Lung carcinoids (LC) are rare tumours, however incidence is increasing due to improvement in diagnostic techniques. They account for approximately 2% of all lung malignancies and around 20-30% of all neuroendocrine tumours (NETs). They characteristically have an indolent clinical behaviour with longer survival intervals compared to poorly differentiated lung neuroendocrine malignancies. LC are divided into typical or atypical carcinoid tumours according to pathological characteristics, such as amount of mitosis and necrosis.
A significant proportion of LC expresses somatostatin receptors by immunohistochemistry. Nuclear medicine imaging, such as somatostatin receptor scintigraphy, has been employed for staging of LC for years. Development of new nuclear medicine imaging techniques, including Positron Emission Tomography (PET) combined with CT has improved diagnosis, staging and treatment of patients diagnosed with LC. 68-Gallium(68Ga)-radiolabelled PET (68Ga-DOTA-PET) tracers for functional NET imaging have emerged as potentially useful tools for diagnosis and staging.
For localised stages of LCs, surgery is the treatment of choice, performed with curative intent. Locally advanced inoperable or metastatic tumours are treated with palliative approaches based on somatostatin analogues (SSAs), temozolomide-based chemotherapy combination and targeted therapies (everolimus). Recently, the use of Peptide Receptor Radionuclide Therapy (PRRT) has revolutionised the treatment of extra-pulmonary neuroendocrine tumours. Based on the results of the NETTER-1 study, PRRT has been approved for the management of small bowel and pancreatic NETs and it is considered a standard of care after progression to SSA for patients with uptake in 68Ga-DOTA-PET (theranostic approach).
This lecture will summarise the state of the art of LC with a focus behind the rationale of PRRT and its potential role in the management of LCs.
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ES04.06 - Systemic Treatment of Large Cell Neuroendocrine Cancer (Now Available) (ID 3173)
10:30 - 12:00 | Presenting Author(s): Fiona Blackhall
- Abstract
- Presentation
Abstract
Large cell neuroendocrine cancer (LCNEC) is a rare, aggressive cancer that accounts for approximately 3% of all lung cancer. It is characterised by high-grade features (>10 mitoses/2mm2) and the presence of neuroendocrine morphology and markers (1). The diagnosis of LCNEC is distinct from both non-small cell lung cancer (NSCLC) and other pulmonary neuroendocrine tumours such as carcinoids and small cell lung cancer (SCLC). Survival is poor with only 5% of patients alive at 5 years from diagnosis regardless of stage at presentation. Conventionally treatment has mirrored that of SCLC despite limited evidence for this approach. The recommended standard of care is a combination of platinum with etoposide based on the results of one single arm phase 2 study in which there were only 29 evaluable patients (2). The median progression free survival (PFS) and overall survival (OS) rates were 5 months and 8 months respectively. Of note the observed objective response rate was 34%, lower than reported ORRs in SCLC of ~70%. Similar worse outcomes in the LCNEC population are observed for treatment with irinotecan and cisplatin (3). The explanation for this disparity is provided by emerging evidence that LCNEC can be subcategorised into two major and clinically relevant subsets according to genomic characteristics (4). A ‘SCLC-like’ genomic profile is estimated to account for about 40% of LCNEC, characterised by RB1 and TP53 that hallmark SCLC and ‘SCLC-like’ LCNEC has clinical behaviour consistent with SCLC. The other subset is ‘NSCLC-like’ with wild-type RB1 as the main distinction alongside mutations that also occur recurrently, at various frequencies, in NSCLC such as STK11, KRAS, KEAP1 and NFE2L2. The latter were hypothesised to be relatively more sensitive to chemotherapy approved for NSCLC. Consistent with this, in a carefully conducted retrospective analysis patients with NSCLC-like LCNEC (RB1 wild type) who received platinum with gemcitabine or a taxane had a median OS of 9.6 months whereas those who received platinum and etoposide had a significantly shorter median OS of 5.8 months (p=0.026) (5). These results question the current standard of care for LCNEC and highlight the need for prospective examination of molecular subtyping to direct treatment decision making. The molecular heterogeneity underpinning LCNEC may also have implications for selection of immune checkpoint inhibitors (6) and other precision medicines targeting actionable mutations (7). The advent of specific KRAS inhibitors that appear promising in early phase development (8) generates further impetus to redesign our therapeutic algorithms for LCNEC according to genomic context if we are to improve outcomes for patients with this orphan disease.
References
1. Travis WD, Brambilla E, Nicholson AG, Yatabe Y, Austin JHM, Beasley MB, et al. The 2015 World Health Organization Classification of Lung Tumors. Journal of Thoracic Oncology.10(9):1243-60.
2. Multicentre phase II study of cisplatin-etoposide chemotherapy for advanced large-cell neuroendocrine lung carcinoma: the GFPC 0302 study. Le Treut J et al. Ann Oncol. 2013: 24(6):1548-52.
3. Combination chemotherapy with irinotecan and cisplatin for large-cell neuroendocrine carcinoma of the lung: a multicentre phase II study. Niho et al. J Thoracic Oncol 2013: 8:980-4
4. Next-Generation Sequencing of Pulmonary Large Cell Neuroendocrine Carcinoma Reveals Small Cell Carcinoma–like and Non–Small Cell Carcinoma–like Subsets. Rekhtman N et al. Clinical Cancer Research. 2016;22(14):3618.
5. Molecular Subtypes of Pulmonary Large-cell Neuroendocrine Carcinoma Predict Chemotherapy Treatment Outcome. Derks JL et al. Clinical Cancer Research. 2018;24(1):33.
6. Genomic Alterations (GA) and Tumor Mutational Burden (TMB) in Large Cell Neuroendocrine Carcinoma of Lung (L-LCNEC) as Compared to Small Cell Lung Carcinoma (SCLC) as Assessed Via Comprehensive Genomic Profiling (CGP). Chae et al. J Clin Oncol 2017; 35:15 suppl, 851
7. Comparison of genomic landscapes of large cell neuroendocrine carcinoma, small cell lung carcinoma, and large cell carcinoma. Zhou Z et al. Thorac Cancer 2019 10(4):839-847
8. Direct Ras G12C Inhibitors : Crossing the Rubicon. Lindsay C and Blackhall F. BJC. 2019 In press
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MA02 - Miscellaneous Topics in the Management of Early Stage Lung Cancer (ID 116)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 2
- Now Available
- Moderators:Mireia Serra-Mitjans, Thomas A. D'Amico
- Coordinates: 9/08/2019, 10:30 - 12:00, Interlaken (1988)
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MA02.02 - Toxicity of Lung SABR in Patients with Coexisting Interstitial Lung Disease (Now Available) (ID 586)
10:30 - 12:00 | Author(s): Ben Slotman
- Abstract
- Presentation
Background
Patients with lung tumors and coexisting interstitial lung disease (ILD) are at increased risk of toxicity following stereotactic ablative radiotherapy (SABR). We report on our institutional experience with SABR in such patients.
Method
Institutional patients undergoing lung SABR with coexisting ILD were identified. ILD subtypes were determined by a pulmonologist specializing in ILD. From late 2015, patients were routinely counseled about the increased treatment risks. Magnetic resonance (MR-)guided SABR was used to reduce target volumes from 2016. Overall and progression-free survival (OS, PFS) were estimated using the Kaplan-Meier method, and dosimetric predictors of radiation pneumonitis (RP) were analyzed based on total lung minus planning target volumes (PTV).
Result
Twenty-four SABR patients treated for lung cancer (n=22) or metastasis (n=2) between 2007-2018 were identified. Median patient age was 74 years, and the commonest ILD diagnosis was idiopathic pulmonary fibrosis. The commonest fractionation schemes were 60 Gy in 8 fractions (n=11), or 55 Gy in 5 fractions (n=6), and SABR was delivered on a Linac (n=17) to a motion-encompassing internal target volume, or with MR-guided SABR (n=7). At median follow-up of 36.9 months (95% CI, 15.8 to not reached), median OS and PFS were 16.6 and 13.3 months, respectively, and 12-month local control was 88.9%. Five patients (20.8%) developed grade ≥3 RP, of which 3 (12.5%) were fatal. Patients with grade ≥3 RP had a higher total lung V20Gy, and a higher ipsilateral and total mean lung dose (MLDEQD2; Fig. 1) than those without (p <.05).
Conclusion
Our findings confirm that ILD patients have a poor prognosis and are at high risk for developing severe RP following SABR. Treatment should be preceded by patient counseling by an experienced ILD team. Careful attention must be given to limiting lung doses, and MR-guided SABR is our preferred approach in such patients.
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MA02.05 - Patient Selection and Early Clinical Outcomes of MR-Guided SABR in 54 Lung Tumors (Now Available) (ID 1318)
10:30 - 12:00 | Author(s): Ben Slotman
- Abstract
- Presentation
Background
Magnetic resonance (MR-)guided stereotactic ablative radiotherapy (SABR) with daily replanning was performed for patients in whom treatment delivery was challenging due to tumor location, motion or pulmonary comorbidity. We describe patient characteristics and early clinical outcomes using this novel approach.
Method
50 consecutive patients (54 lung tumors) underwent MR-guided SABR at a single center between 2016-2018 for either primary lung cancer (n = 29 tumors) or lung metastases (n = 25). Patients had one or more factors predisposing to toxicity, including a central tumor location (n = 27 patients), previous thoracic radiotherapy (n = 17), and interstitial lung disease (n = 7). A daily 17-second breath-hold MR scan was acquired in treatment position, followed by on-table plan adaptation. Gated delivery was performed using repeated breath-holds under continuous MR-guidance. Local control, overall (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method, with PFS defined as time to disease progression or death from any cause.
Result
Breath-hold SABR delivery was well tolerated, with all but one patient completing the planned schedule. With daily replanning, a biologically equivalent dose (BED10Gy) ≥100Gy to 95% of the planning target volume was delivered in 51 tumors (94%). Median follow-up was 15.8 months (95% CI, [11.4-22.5]). Local control, OS and PFS at 12 months were 93.4%, 86.7% and 58.4%, respectively (Fig. 1). In-field recurrences developed in 2 patients who were re-irradiated for a local recurrence after previous SABR, and one marginal recurrence was observed. Overall rates of any grade ≥2 and ≥3 toxicity were 24% and 4%, respectively. No grade ≥4 toxicity was seen. Commonest toxicities were grade ≥2 radiation pneumonitis (8%) and chest wall pain (8%; including one rib fracture).
Conclusion
Early follow-up of the largest patient cohort to date undergoing thoracic MR-guided SABR indicates low toxicity rates, and promising local tumor control.
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P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.17-26 - Delivery of Stereotactic MR-Guided Adaptive Radiation Therapy for Peripheral Lung Tumors (ID 1368)
09:45 - 18:00 | Author(s): Ben Slotman
- Abstract
Background
Stereotactic MR-guided adaptive radiation therapy (SMART) allows delivery of stereotactic ablative radiotherapy (SABR) with high precision (van Sörnsen de Koste JR, 2018). For central lung tumors, SMART with on-table plan adaptation improves target coverage and avoids excessive normal organ doses (Finazzi T, 2019). The benefits of SMART for peripherally located lung tumors are unknown.
Method
Between 2016-2019, 23 patients (25 peripheral lung tumors) underwent SMART delivered in 3-8 fractions on an MR-Cobalt-60 system or MR-Linac. Before each fraction, a 17-second breath-hold MR scan was acquired, followed by on-table plan adaptation based on the anatomy-of-the-day, using a planning target volume (PTV) margin of 3 or 5 mm. Breath-hold gated delivery was performed under continuous MR-guidance using an in-room monitor (Fig. 1). For 14 patients, a motion-encompassing internal target volume (ITV) was created from a free-breathing 4DCT scan. Benefits of on-table adaptation were studied by comparing 112 «predicted» plans, which are the baseline plans recalculated on the anatomy-of-the-day, with on-table reoptimized plans.
Result
The SMART procedure took a median of 62 minutes on the MR-Cobalt-60 system, and 48 minutes on MR-Linac. Average SMART-PTVs were 15.4 cc (range, [3.1-55.6]). In 14 patients with a 4DCT, SMART-PTVs measured only 53.7% (range, [31.9-75.0]) of PTVs generated from the corresponding 4DCT scans (ITV+5mm). Clinicians chose the reoptimized plan for 91% of fractions. Per fraction, on-table plan adaptation improved prescription dose coverage (V100%) of the PTV from a median of 92.2% in predicted plans, to 95.0% in reoptimized ones, thereby increasing the proportion of fractions delivering a BED10Gy ≥100Gy to 95% of PTV from 90.2% to 100.0%.
Conclusion
Using SMART for peripheral lung tumors resulted in smaller target volumes, and on-table plan adaptation ensured delivery of ablative doses to the PTV. Despite longer SABR delivery times, our findings suggest that SMART can be beneficial for some peripheral lung tumors.
