# Radiation Oncology/NSCLC/Lung Brachytherapy

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Lung Brachytherapy

## Guidelines

* American Brachytherapy Society; 2001 PMID 11301833 -- "Brachytherapy for carcinoma of the lung." (Nag S, Oncology (Williston Park). 2001 Mar;15(3):371-81.)

## Limited Resection with Intraoperative Brachytherapy

* ACOSOG Z4032 -- sublobar resection versus sublobar resection + brachytherapy
** Randomized. 222 patients. Median age 71. Surgery versus surgery + brachytherapy. Inclusion criteria: tumor ≤ 3 cm; and high risk (FEV1<50% predicted, DLCO <50% predicted or age >75, exertional dyspnea, borderline PFTs)
** 2007 PMID 17909906 -- "Dosimetric evaluation of radiation exposure during I-125 vicryl mesh implants: implications for ACOSOG z4032." (Smith RP, Ann Surg Oncol. 2007 Dec;14(12):3610-3. Epub 2007 Oct 2.)
*** Dosimetry. 22 patients. I-125 vicryl mesh implants, 40-60 seeds. Median activity 0.5 mCi per seed, median total activity 23 mCi
*** Outcome: median dose to radiation oncologist 1 mrem, surgery 2 mrem, control diode on patient 5.4 mrerm/h
*** Conclusion: Very little radiation exposure to physicians and staff during segmentectomy and I-125 vicryl mesh implantation
** 2014 PMID 24982457 -- "Impact of Brachytherapy on Local Recurrence Rates After Sublobar Resection: Results From ACOSOG Z4032 (Alliance), a Phase III Randomized Trial for High-Risk Operable Non-Small-Cell Lung Cancer." (Fernando HC, J Clin Oncol. 2014 Aug 10;32(23):2456-62. doi: 10.1200/JCO.2013.53.4115. Epub 2014 Jun 30.). Median F/U 4.4 years
*** Outcome: 5-year OS surgery 61% vs surgery + brachytherapy 56% (NS). 5-year LR 14% vs 17% (NS); no difference in time to recurrence or pattern of local recurrence. Local recurrence/death 43% vs 49% (NS)
*** Conclusion: Brachytherapy did not reduce local recurrence after sublobar resection
* Multi-Institutional; 2005 PMID 15678034 -- "Lobar and sublobar resection with and without brachytherapy for small stage IA non-small cell lung cancer." (Fernando HC, J Thorac Cardiovasc Surg. 2005 Feb;129(2):261-7.)
** Retrospective. 4 institutions (Pittsburgh, UCLA, City of Hope, Allegheny General). 291 patients with T1N0. Sublobar resection (n=124) compared with lobar resection (n=167). Brachytherapy in 48% of sublobar operations. Sublobar patients older (SS), worse pulmonary function (SS). Mean F/U 2.9 years
** Outcome: Sublobar LR no brachy 17% vs. brachy 3%. No difference in OS in small tumors (<2 cm). Significantly better OS in large tumors (2-3cm) lobar 5.8 years vs. sublobar 4 years (SS)
** Conclusion: Intraop brachy may reduce LR with small tumors
* Pittsburgh; 2003 PMID 14605631 -- "Comparison between sublobar resection and 125Iodine brachytherapy after sublobar resection in high-risk patients with Stage I non-small-cell lung cancer." (Santos R, Surgery. 2003 Oct;134(4):691-7; discussion 697.)
** Retrospective. 203 patients. 102 Stage IA treated 1989-1994 with surgery alone, 101 patients Stage IA-B treated 1997-2002 with surgery + intraoperative I-125 BT. BT mesh placed over staple line
** Recurrence: local - surgery alone 19% vs. surgery + BT 2% (SS), systemic 28% vs. 22% (NS)
** Toxicity: no difference in periop mortality or hospital stay
** Conclusion: Safe, should be considered in compromised patients
* Tufts; 2003 PMID 12537222 -- "Limited resection for non-small cell lung cancer: observed local control with implantation of I-125 brachytherapy seeds." (Lee W, Ann Thorac Surg. 2003 Jan;75(1):237-42; discussion 242-3.)
** Retrospective. 33 patients with 35 NSCLC, limited resection + brachytherapy I-125 seeds. Median F/U 4.2 years
** Outcome: 5-year OS 47%, T1N0 67%, T2N0 39%. Cancer-specific survival 77% and 53%
** Recurrence: overall 29%, local 6%, regional 17%
** Conclusion: Brachytherapy I-125 implantation gives low local recurrence, may prolong survival
Review
* Royal Surrey; 2008 (UK) PMID 19056322 -- "Intraoperative seed placement for thoracic malignancy-A review of technique, indications, and published literature." (Stewart AJ, Brachytherapy. 2008 Dec 2. [Epub ahead of print])
** Summary of methods of brachytherapy seed placement and the published experience of brachytherapy implants within the thorax; radiation safety and postoperative dosimetry also reviewed
Aorta RT Tolerance
* Please see the Aorta Toxicity section

## Definitive Endobronchial Brachytherapy

* MSKCC Experience PMID 3027826 -- "Intraoperative radiotherapy in stage I and II lung cancer." (Hilaris B, Seminars in Surgical Oncology. 1987;3(1):22-32.)
** Treated patients with brachy alone from 1950's to 1980's who were unable to tolerate surgical resection.
** Median survival of 2.6 years
** 53% local control

## Palliative Endobronchial Brachytherapy

Systematic Review
* Cochrane Review; 2008 PMID 18425900 -- "Palliative endobronchial brachytherapy for non-small cell lung cancer." (Cardona A, Cochrane Database Syst Rev. 2008 Apr 16;(2):CD004284.)
** 13 randomized trials; meta-analysis not attempted due to heterogeneity of patients and treatments.
** Outcome: EBRT alone more effective for palliation than EBB alone. No conclusive evidence to recommend EBRT + EBB compared with EBRT alone.
* Cancer Care Ontario; 2006 PMID 16864071 -- "The role of high-dose-rate brachytherapy in the palliation of symptoms in patients with non-small-cell lung cancer: a systematic review." (Ung YC, Brachytherapy. 2006 Jul-Sep;5(3):189-202.)
** 29 trials
** Outcome:
*** Previously untreated patients: EBRT alone more effective than HDRBT. HDRBT with EBRT seems better symptoms relief than EBRT alone
*** Previously treated patients: HDRBT recommended, provided it is technically feasible
** Toxicity: Fatal hemoptysis ranged from 7% to 22%
Retrospective Evidence
* Novi Sad, Serbia; 2010 PMID 20439194 -- "Clinical risk factors for early complications after high-dose-rate endobronchial brachytherapy in the palliative treatment of lung cancer." (Zaric B, Clin Lung Cancer. 2010 May;11(3):182-6.)
** Retrospective. 761 patients, advanced-stage lung cancer, HDRBT as part of multimodality therapy.
** Outcome: Complication rate 5.4%. Predictors for complications: HTN, chronic cardiac arrhythmias, COPD, cardiomyopathy
** Conclusion: Closer monitoring of patients with identified risk factors is advisable
* Heidelberg; 2010 (1987-2005) PMID 19836162 -- "Treatment of recurrent bronchial carcinoma: the role of high-dose-rate endoluminal brachytherapy" (Hauswald H, Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):373-7. Epub 2009 Oct 14.)
** Retrospective. 41 patients, prior EBRT (median dose 56 Gy), retreatment with HDRBT for symptomatic recurrence. Median dose 15 Gy (5-29 Gy), median time-to-irradiation 9 months (2-54). Median F/U 7 months
** Outcome: Initial local control 73%; LC 6-months 38%, 1-year 17%. OS 6-months 58%, 1-year 18%. Median LC PFS 4 months
** Toxicity: Fatal hemorrhage 15%; no Grade 3-4 toxicity in patients with locally controlled disease
** Conclusion: Palliative retreatment with HDRBT can be effective, causing only few complications
* Poznan, Poland; 2009 PMID 19854525 -- "HDR endobronchial brachytherapy (HDRBT) in the management of advanced lung cancer--comparison of two different dose schedules." (Skowronek J, Radiother Oncol. 2009 Dec;93(3):436-40. Epub 2009 Oct 23.)
** Retrospective. 648 patients, advanced lung cancer. Palliative HDRBT doses schedules 22.5/3 once/week (47%) or 10/1 (53%)
** Outcome: No difference in survival, similar efficacy in overcoming difficulties in breathing
** Conclusion: Similar efficiency between the two treatment protocols
* MD Anderson, 2000 PMID 11020566 -- "High-Dose-Rate Endobronchial Brachytherapy effectively palliates symptoms due to airway tumors: The 10-year M.D. Anderson Cancer Center Experience." (Kelly, J. Int J Radiat Oncol Biol Phys. 2000;48(3):697-702.)
** 175 patients who underwent HDR
** 15 Gy at 6mm most common Rx
** 66% patients show symptomatic improvement
** 2nd look bronchoscopy showed 78% objective response rate
** 13% actuarial complication rate at 1 year
* Indiana University, 1994 PMID 7509330 -- "High dose rate afterloading intraluminal brachytherapy in malignant airway obstruction of lung cancer." (Chang, LF. Int J Radiat Oncol Biol Phys. 1994 Feb 1;28(3):589-96.
** 76 pts (225 HDR applications); 59 received concurrent external beam, 1pt w/ concurrent xrt
** 7 Gy to 1cm; 3 fractions at 2 wk intervals
** 87% response rate for dyspnea (28% CR)
** 95% response rate for hemoptysis (57% CR)
** 4 acute complications (3 massive hemoptysis, 1 mild hemoptysis).