Portal de Periódicos da CAPES

Stereotactic body radiotherapy for bilateral primary lung cancers: The Indiana University experience

2006; Elsevier BV; Volume: 66; Issue: 4 Linguagem: Inglês

10.1016/j.ijrobp.2006.06.042

1879-355X

Bedatri Sinha, Ronald C. McGarry,

Advanced Radiotherapy Techniques

Purpose: To review the outcomes of 10 patients treated with stereotactic body radiotherapy for bilateral primary medically inoperable lung cancer.Methods and Materials: Between July 2001 and February 2005, 10 patients were treated at Indiana University with stereotactic body radiotherapy for bilateral multiple primary lung cancers using a stereotactic body frame (Elekta, Stockholm, Sweden). Nine patients had cancers that were deemed inoperable secondary to multiple medical comorbidities. One patient refused surgery. All patients had biopsy proven non–small-cell lung carcinoma of at least one of their masses and presented with either metachronous or synchronous pulmonary nodules. Positron emission tomography scans were done for all patients before treatment. Radiation dose varied between 4800 and 6600 cGy given in 3 fractions prescribed to the 80% line covering at least 95% of the planning target volume. We performed a retrospective review of the outcome of these patients.Results: The mean follow-up time was 20.7 months and the median time was 18.5 months (range, 7–42 months). At the time of this review, all 10 patients were living. Eight (80%) of 10 patients had no evidence of disease progression. One patient developed distant metastasis 5 months after treatment and a second patient developed a local recurrence within the radiation field 11 months after treatment. Six patients had either acute or late pulmonary toxicity, but all toxicity was ≤Grade 2 as defined by the Radiation Therapy Oncology Group toxicity criteria.Conclusion: Our preliminary results indicate that stereotactic body radiotherapy is a possibly safe and potentially effective treatment option for patients with bilateral multiple primary lung cancers that are deemed medically inoperable. Purpose: To review the outcomes of 10 patients treated with stereotactic body radiotherapy for bilateral primary medically inoperable lung cancer. Methods and Materials: Between July 2001 and February 2005, 10 patients were treated at Indiana University with stereotactic body radiotherapy for bilateral multiple primary lung cancers using a stereotactic body frame (Elekta, Stockholm, Sweden). Nine patients had cancers that were deemed inoperable secondary to multiple medical comorbidities. One patient refused surgery. All patients had biopsy proven non–small-cell lung carcinoma of at least one of their masses and presented with either metachronous or synchronous pulmonary nodules. Positron emission tomography scans were done for all patients before treatment. Radiation dose varied between 4800 and 6600 cGy given in 3 fractions prescribed to the 80% line covering at least 95% of the planning target volume. We performed a retrospective review of the outcome of these patients. Results: The mean follow-up time was 20.7 months and the median time was 18.5 months (range, 7–42 months). At the time of this review, all 10 patients were living. Eight (80%) of 10 patients had no evidence of disease progression. One patient developed distant metastasis 5 months after treatment and a second patient developed a local recurrence within the radiation field 11 months after treatment. Six patients had either acute or late pulmonary toxicity, but all toxicity was ≤Grade 2 as defined by the Radiation Therapy Oncology Group toxicity criteria. Conclusion: Our preliminary results indicate that stereotactic body radiotherapy is a possibly safe and potentially effective treatment option for patients with bilateral multiple primary lung cancers that are deemed medically inoperable. IntroductionMultiple primary lung cancer (MPLC) has been described for many decades; however, its prevalence still remains largely unknown (1Rea F. Zuin A. Callegaro D. et al.Surgical results for multiple primary lung cancers.Eur J Cardiothorac Surg. 2001; 20: 489-495Crossref PubMed Scopus (60) Google Scholar, 2Antakli T. Schaefer R. Rutherford J. et al.Second primary lung cancer.Ann Thorac Surg. 1995; 59: 863-866Abstract Full Text PDF PubMed Scopus (172) Google Scholar, 3Tsunezuka Y. Matsumoto I. Tamura M. et al.The results of therapy for bilateral multiple primary lung cancers: 30 years experience in a single centre.Eur J Surg Oncol. 2004; 30: 781-785Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 4Nakata M. Sawada S. Yamashita M. et al.Surgical treatments for multiple primary adenocarcinoma of the lung.Ann Thorac Surg. 2004; 78: 1194-1199Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 5Aziz T.M. Saad R.A. Glasser J. et al.The management of second primary lung cancers A single centre experience in 15 years.Eur J Cardiothorac Surg. 2002; 21: 527-533Crossref PubMed Scopus (95) Google Scholar, 6Adebonojo S.A. Moritz D.M. Danby C. et al.The results of modern surgical therapy for multiple primary lung cancers.Chest. 1997; 112: 693-701Crossref PubMed Scopus (104) Google Scholar, 7Martini N. Melamed M.R. Multiple primary lung cancers.J Thorac Cardiovasc Surg. 1975; 70: 606-612PubMed Google Scholar). The risk of developing metachronous pulmonary lung cancers after surgical resection of early-stage lung cancer has been estimated at 2% to 3% per year (1Rea F. Zuin A. Callegaro D. et al.Surgical results for multiple primary lung cancers.Eur J Cardiothorac Surg. 2001; 20: 489-495Crossref PubMed Scopus (60) Google Scholar, 2Antakli T. Schaefer R. Rutherford J. et al.Second primary lung cancer.Ann Thorac Surg. 1995; 59: 863-866Abstract Full Text PDF PubMed Scopus (172) Google Scholar). Often times these patients have significant comorbidities that preclude bi-lobectomy or pneumonectomy and thus present physicians with treatment dilemmas.Beginning in 1999, a study of the use of stereotactically-targeted radiation therapy for the curative treatment of solitary early-stage non–small-cell lung cancer in patients who were unable to undergo curative surgery by virtue of medical comorbidities was undertaken at Indiana University. Since then we have completed a Phase I and Phase II study to define appropriate doses and confirm the safety of this technology. During the course of this study, 10 patients were found to have either multiple, or more specifically, bilateral, independent malignant pulmonary nodules at initial workup or subsequently in the course of their disease (8McGarry R.C. Papiez L. Williams M. et al.Stereotactic body radiation therapy of early-stage non–small-cell lung carcinoma: phase I study.Int J Radiat Oncol Biol Phys. 2005; 63: 1010-1015Abstract Full Text Full Text PDF PubMed Scopus (417) Google Scholar, 9Timmerman R. Papiez L. McGarry R.C. et al.Extracranial stereotactic radioablation: Results of a phase I study in medically inoperable stage I non-small cell lung cancer.Chest. 2003; 124: 1946-1955Crossref PubMed Scopus (590) Google Scholar). The criteria set by Martini and Melamed (7Martini N. Melamed M.R. Multiple primary lung cancers.J Thorac Cardiovasc Surg. 1975; 70: 606-612PubMed Google Scholar) or the modified version by Antakli (2Antakli T. Schaefer R. Rutherford J. et al.Second primary lung cancer.Ann Thorac Surg. 1995; 59: 863-866Abstract Full Text PDF PubMed Scopus (172) Google Scholar) were used to differentiate independently arising lung cancers from metastatic disease. The cancer in the majority of patients was deemed medically inoperable and patients had few options for further treatment. Therefore they elected to undergo stereotactic radiation therapy. In a review of the literature, there is data available on surgical outcomes of patients with resected multiple or bilateral primary lung cancers (1Rea F. Zuin A. Callegaro D. et al.Surgical results for multiple primary lung cancers.Eur J Cardiothorac Surg. 2001; 20: 489-495Crossref PubMed Scopus (60) Google Scholar, 3Tsunezuka Y. Matsumoto I. Tamura M. et al.The results of therapy for bilateral multiple primary lung cancers: 30 years experience in a single centre.Eur J Surg Oncol. 2004; 30: 781-785Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 4Nakata M. Sawada S. Yamashita M. et al.Surgical treatments for multiple primary adenocarcinoma of the lung.Ann Thorac Surg. 2004; 78: 1194-1199Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 5Aziz T.M. Saad R.A. Glasser J. et al.The management of second primary lung cancers A single centre experience in 15 years.Eur J Cardiothorac Surg. 2002; 21: 527-533Crossref PubMed Scopus (95) Google Scholar, 6Adebonojo S.A. Moritz D.M. Danby C. et al.The results of modern surgical therapy for multiple primary lung cancers.Chest. 1997; 112: 693-701Crossref PubMed Scopus (104) Google Scholar); however there is virtually no published data on management alternatives or outcomes of patients with medically inoperable cancers.The purpose of this retrospective review is to evaluate the toxicity and disease control with stereotactic body radiation therapy (SBRT) for bilateral MPLC in the medically inoperable patient population.Methods and materialsPatientsThe charts of 10 patients with bilateral MPLC treated between 2001 and 2005 were reviewed. All patients had biopsy-proven non–small-cell lung carcinoma of at least one of their masses and presented with either metachronous or synchronous pulmonary nodules (Table 1). Staging included pretreatment positron emission tomography (PET) scans to exclude systemic metastases or mediastinal disease. Four patients had posttreatment PET scans. In patients with metachronous disease, a PET-computed tomography (CT) was obtained before the treatment of each lesion. All 10 patients were evaluated by a thoracic surgeon who ultimately deemed 9 to have medically inoperable tumors secondary to multiple medical comorbidities, or to have unacceptable pulmonary function. Medical comorbidities included severe chronic obstructive pulmonary disease, coronary artery disease, peripheral vascular disease, poorly controlled hypertension, and diabetes. Standard "cut-off" guidelines rendering patients poor candidates for surgical resection included the following: baseline forced expiratory volume at one second (FEV1) ≤40% predicted; likely postoperative FEV1 ≤30% predicted; severely reduced diffusion capacity ≤40% predicted; baseline hypoxemia (i.e., ≤70 mm Hg [a relative contraindication]) and/or hypercapnia (i.e., ≤50 mm Hg); and exercise oxygen consumption ≤50% predicted. One patient included in this series had resection of 1 lesion and developed a second metachronous lesion. Specific criteria for the diagnosis of MPLC were used (Table 2).Table 1Patient characteristicsNo. of patients (%) n = 10Gender Male1 (10%) Female9 (90%)Histologic type of first cancer⁎One patient had biopsy of both masses. Adenocarcinoma5 (45%) Squamous cell3 (27%) Large cell1 (9%) NSCLC NOS2 (18%)Presentation Synchronous8 (73%) Metachronous3 (27%)Stage of presentation First mass T17 (70%) T23 (30%) Second mass T18 (80%) T22 (20%) Third mass T11 (100%)Abbreviations: NSCLC = non–small-cell lung cancer; NOS = not otherwise specified. One patient had biopsy of both masses. Open table in a new tab Table 2Criteria for diagnosis of MPLCMartini and Melamed, 1975 (7Martini N. Melamed M.R. Multiple primary lung cancers.J Thorac Cardiovasc Surg. 1975; 70: 606-612PubMed Google Scholar)Metachronous tumorsIHistologic type differentIIHistologic type the same if:aFree interval between cancer is at least 2 yearsbOrigin from carcinoma in situcSecond cancer is in different lobe or lung but:iNo carcinoma in lymphatics common to bothiiNo extrapulmonary metastases at the time of diagnosisSynchronous tumorsITumors physically distinct and separateIIHistologic typeaDifferentbSame, but in different segment, lobe, or lung, if:iOrigin from carcinoma in situiiNo carcinoma in lymphatics common to bothiiiNo extrapulmonary metastases at time of diagnosisAntakli et al. 1995 (2Antakli T. Schaefer R. Rutherford J. et al.Second primary lung cancer.Ann Thorac Surg. 1995; 59: 863-866Abstract Full Text PDF PubMed Scopus (172) Google Scholar)IDifferent histologic conditionIISame histologic condition with two or more of the following:aAnatomically distinctbAssociated premalignant lesioncNo systemic metastasesdNo mediastinal spreadeDifferent DNA ploidyAbbreviation: MPLC = Multiple primary lung cancer. Open table in a new tab RadiotherapyDetails of the radiation therapy have been published elsewhere (8McGarry R.C. Papiez L. Williams M. et al.Stereotactic body radiation therapy of early-stage non–small-cell lung carcinoma: phase I study.Int J Radiat Oncol Biol Phys. 2005; 63: 1010-1015Abstract Full Text Full Text PDF PubMed Scopus (417) Google Scholar, 9Timmerman R. Papiez L. McGarry R.C. et al.Extracranial stereotactic radioablation: Results of a phase I study in medically inoperable stage I non-small cell lung cancer.Chest. 2003; 124: 1946-1955Crossref PubMed Scopus (590) Google Scholar). Briefly, patients were positioned in the stereotactic body frame (Elekta, Stockholm, Sweden) in a vacuum pillow to create a reproducible immobilization device. Prepatellar and sternal positioning marks were permanently applied. Abdominal clamping pressure was applied until the motion of the diaphragm (or tumor, if visible) was reduced to 1.0 cm or less on fluoroscopy. Specific measurements of motion, pre-, and postabdominal compression, were not recorded. CT-guided simulation was done and the gross tumor volume (GTV) was defined. Atelectasis was not included in GTV. This was often differentiated by PET-CT. No specific margin was added for microscopic disease extension. No nodal irradiation was attempted. An additional 0.5 cm in the axial plane and 1.0 cm in the longitudinal plane was added to the GTV to constitute the planning target volume (PTV). Three-dimensional treatment planning, using 7 to 10 noncoplanar, nonopposing beams, were used for treatment. Six-mV (and, less frequently, 15-mV) photons were stereotactically directed toward the tumor. Heterogeneity corrections were not used. Normal tissue tolerance limits were used according to our institutional standards (Table 3). During planning of these patients, if PET-positive nodules were detected synchronously, preplanning of both treatment fields was done to assess for feasibility of treating both nodules. For metachronous nodules, composite plans were done to assess safety with respect to dose-limiting organs and limited according to fraction size received and total dose according to our standards. Radiation dose varied between 4800 and 6600 cGy given, depending on the location of the mass and proximity to normal tissues, and to remain within our institutional normal tissue limits (Table 3). Treatment was delivered in 3 to 4 fractions. Dose was prescribed to the 80% line covering at least 95% of the PTV (8McGarry R.C. Papiez L. Williams M. et al.Stereotactic body radiation therapy of early-stage non–small-cell lung carcinoma: phase I study.Int J Radiat Oncol Biol Phys. 2005; 63: 1010-1015Abstract Full Text Full Text PDF PubMed Scopus (417) Google Scholar, 9Timmerman R. Papiez L. McGarry R.C. et al.Extracranial stereotactic radioablation: Results of a phase I study in medically inoperable stage I non-small cell lung cancer.Chest. 2003; 124: 1946-1955Crossref PubMed Scopus (590) Google Scholar) (Fig. 1). Radiation fractions were separated by 1 to 2 days. Sequential treatment of synchronous primaries was separated by 1 month, except in 1 patient whose second mass was treated 10 days after the treatment completion of her first mass secondary to personal patient factors. The usual policy was to treat the largest lesion first. The CT scan and planning was repeated before treatment of the second lesion if treatment time between the 2 lesions was greater than 3 weeks. Dose to both lesions was usually, but not always, the same.Table 3Normal tissue tolerance limitsOrgan (any volume)DoseSpinal cord18 Gy (6 Gy per fraction)Esophagus23 Gy (9 Gy per fraction)Ipsilateral brachial plexus24 Gy (8 Gy per fraction)Heart30 Gy (10 Gy per fraction)Trachea and ipsilateral bronchus30 Gy (10 Gy per fraction) Open table in a new tab Follow-upPatients were followed with physical examination and chest x-ray or chest CT scans. The first follow-up visits were approximately 4 to 6 weeks posttreatment, at which time a chest x-ray was obtained. After this time, follow-up visits were every 2 to 4 months with chest CT at each visit for the first year and then every 6 months thereafter unless otherwise indicated. Post-treatment PET-CTs were only obtained if there were suspicious findings on chest CT or by history or physical examination.ResultsPatientsNine patients had 2 masses and one had 3 masses. One patient had resection of the first mass and SBRT of the second. One patient had mediastinoscopy before treatment. Nine patients (90%) were women. The mean patient age was 67.4 years and the median was 65.5 years (range, 55–78 years). Eight patients presented with synchronous masses and 3 presented with metachronous masses. The patient with 3 masses initially presented with 2 synchronous masses, then a third metachronous mass. The time for development of a metachronous mass ranged from 3 to 27 months. Nine patients had cancers that were deemed medically inoperable for one or both of their masses and 1 patient refused surgery (Table 1).All 10 patients (100%) are alive at time of this review (Table 4). The mean follow-up time was 20.7 months and the median time was 18.5 months (range, 7–42 months). Two of the 10 patients (20%) had progression, 1 local, and 1 distant (brain). The patient with distant metastasis presented with disease 5 months after treatment of the second mass. This patient presented with synchronous masses and had biopsy of only 1 mass with a PET-CT showing no hypermetabolic activity in the mediastinum. The histology of the mass biopsied was adenocarcinoma. The patient with local progression had local recurrence within the radiation field. This was detected 11 months after treatment of the third mass. This was also the only patient that had treatment to 3 separate lesions (2 presented synchronously and 1 metachronously). All three of this patient's masses were treated to 60 Gy in 3 fractions prescribed to the 80% isodose line. The remaining 8 (80%) patients had stable disease or regression. Three (30%) patients had acute pulmonary complications, all of which were ≤Grade 2 as per the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Five (50%) patients had late pulmonary complications, all of which were Grade 1 as per the RTOG toxicity criteria. The time between treatment of the separate masses ranged between 10 days and 11 months, with a median time of 2 months.Table 4Treatment outcomePatientDose (Gy)ToxicitySurvival (m)RecurrenceLesion 1, lesion 2Acute/grade Late/gradeLocal/distant Time to progression148, 48None42NoneGrade 1260, 60Grade 27NoneNone360, 60None13DistantUnknown5 months460, 60, 60Grade 133LocalGrade 111 months566, 50None22NoneNone654, 48None23NoneNone760, 60Grade 225NoneGrade 1860, 60None12NoneUnknown954, 54None15NoneGrade 110Resection, 66None15NoneGrade 1 Open table in a new tab Although all patients had pretreatment PET scans, only 4 patients had post-treatment PET scans. PET scan detected the local recurrence in the 1 patient with local progression. The PET scan identified a hypermetabolic area (increased standardized uptake value [SUV]), which correlated with the area of significant enlargement on chest CT scans (within the radiation field). The remaining 3 patients had PET scans with low-to-minimum residual hypermetabolic activity with low probability of recurrence. Serial PET scans were not obtained unless other suspicious findings were found on CT or other work-up.DiscussionMultiple primary lung cancers were first described in the 1920s (1Rea F. Zuin A. Callegaro D. et al.Surgical results for multiple primary lung cancers.Eur J Cardiothorac Surg. 2001; 20: 489-495Crossref PubMed Scopus (60) Google Scholar, 5Aziz T.M. Saad R.A. Glasser J. et al.The management of second primary lung cancers A single centre experience in 15 years.Eur J Cardiothorac Surg. 2002; 21: 527-533Crossref PubMed Scopus (95) Google Scholar). Although the incidence is not clear, several authors have reported incidences from 0.5% to 10% (1Rea F. Zuin A. Callegaro D. et al.Surgical results for multiple primary lung cancers.Eur J Cardiothorac Surg. 2001; 20: 489-495Crossref PubMed Scopus (60) Google Scholar, 2Antakli T. Schaefer R. Rutherford J. et al.Second primary lung cancer.Ann Thorac Surg. 1995; 59: 863-866Abstract Full Text PDF PubMed Scopus (172) Google Scholar, 3Tsunezuka Y. Matsumoto I. Tamura M. et al.The results of therapy for bilateral multiple primary lung cancers: 30 years experience in a single centre.Eur J Surg Oncol. 2004; 30: 781-785Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 4Nakata M. Sawada S. Yamashita M. et al.Surgical treatments for multiple primary adenocarcinoma of the lung.Ann Thorac Surg. 2004; 78: 1194-1199Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 5Aziz T.M. Saad R.A. Glasser J. et al.The management of second primary lung cancers A single centre experience in 15 years.Eur J Cardiothorac Surg. 2002; 21: 527-533Crossref PubMed Scopus (95) Google Scholar, 6Adebonojo S.A. Moritz D.M. Danby C. et al.The results of modern surgical therapy for multiple primary lung cancers.Chest. 1997; 112: 693-701Crossref PubMed Scopus (104) Google Scholar, 7Martini N. Melamed M.R. Multiple primary lung cancers.J Thorac Cardiovasc Surg. 1975; 70: 606-612PubMed Google Scholar) in lung cancer patients. The risk of developing a second lung cancer in patients who have been treated with surgical resection for an early-stage lung cancer is approximately 1% to 2% per year. MPLCs may appear as synchronous or metachronous, unilateral or bilateral. An obvious dilemma is differentiating true second primary lung cancers from metastatic disease, and diagnostic criteria have been proposed for distinguishing the two (2Antakli T. Schaefer R. Rutherford J. et al.Second primary lung cancer.Ann Thorac Surg. 1995; 59: 863-866Abstract Full Text PDF PubMed Scopus (172) Google Scholar, 7Martini N. Melamed M.R. Multiple primary lung cancers.J Thorac Cardiovasc Surg. 1975; 70: 606-612PubMed Google Scholar) (Table 2). Unfortunately, given the patient population, it was often deemed too high risk to obtain multiple biopsies or perform mediastinoscopy; therefore, the histologic classification of the second cancer or the pathologic status of the mediastinum was often not known. However, within the patient group under study, all patients had bilateral disease and negative PET imaging, suggesting no metastatic or mediastinal disease. Therefore, this was strongly suggestive of, but not definitive proof that, the lesions were distinct cancers.Although only limited conclusions can be made from small retrospective series with such a large range of follow-up times, some interesting trends were observed. We can report that with a median follow-up time of 18.5 months, 80% of patients showed no evidence of disease progression and 100% of patients were living. Of the 10 patients, only two showed progression at the time of this review. One had brain metastasis that presented within 5 months of treatment of the second lesion. Microscopic metastasis not visible on radiographic imaging may have been present at the time of the second treatment. The second patient had local progression. Interestingly, this patient was also the only one to have 3 lung nodules (2 synchronous and 1 metachronous). All 3 masses were treated with stereotactic radiotherapy and there was progression of only the last mass treated. By virtue of having the largest number of lesions, they would have a higher likelihood of progression of one of their lesions, as well as a higher probability of one of the lesions being a metastasis rather than an additional primary tumor. In the present series, 50% of the patients had >20-month follow-up with no evidence of disease progression. In addition, all patients tolerated treatment very well and no patient presented with >Grade 2 pulmonary complications, either in the acute or chronic setting.Multiple primary lung cancers have historically been managed by surgical resection. Several studies have been published regarding the outcomes of these patients (1Rea F. Zuin A. Callegaro D. et al.Surgical results for multiple primary lung cancers.Eur J Cardiothorac Surg. 2001; 20: 489-495Crossref PubMed Scopus (60) Google Scholar, 2Antakli T. Schaefer R. Rutherford J. et al.Second primary lung cancer.Ann Thorac Surg. 1995; 59: 863-866Abstract Full Text PDF PubMed Scopus (172) Google Scholar, 3Tsunezuka Y. Matsumoto I. Tamura M. et al.The results of therapy for bilateral multiple primary lung cancers: 30 years experience in a single centre.Eur J Surg Oncol. 2004; 30: 781-785Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 4Nakata M. Sawada S. Yamashita M. et al.Surgical treatments for multiple primary adenocarcinoma of the lung.Ann Thorac Surg. 2004; 78: 1194-1199Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 5Aziz T.M. Saad R.A. Glasser J. et al.The management of second primary lung cancers A single centre experience in 15 years.Eur J Cardiothorac Surg. 2002; 21: 527-533Crossref PubMed Scopus (95) Google Scholar, 6Adebonojo S.A. Moritz D.M. Danby C. et al.The results of modern surgical therapy for multiple primary lung cancers.Chest. 1997; 112: 693-701Crossref PubMed Scopus (104) Google Scholar, 7Martini N. Melamed M.R. Multiple primary lung cancers.J Thorac Cardiovasc Surg. 1975; 70: 606-612PubMed Google Scholar). Reported 5-year survivals from surgical series have varied greatly and ranged from 10% to 70% for synchronous cancers and 44% to 85% for metachronous lesions (since development of second lesion). Roberts et al. (10Roberts J.R. Schumaker D. et al.An algorithm for managing bilateral lung masses [Abstract].J Clin Oncol. 2004; 22: 7371Google Scholar) presented an algorithm for the treatment of bilateral lung masses. They analyzed 36 patients with bilateral lung masses (with negative mediastinoscopies) and bilateral resections. They found that patients with a similar pathology in bilateral lung masses had the lowest survival at 24 months. They concluded that only patients with different pathology of bilateral lung masses should have resection and those with identical pathologies should undergo chemoradiotherapy. Unfortunately, few of our patients received biopsy of their second mass secondary to multiple factors. The majority of patients had cancers that were not medically operable, secondary to multiple comorbidities and/or poor performance status. Therefore, with 1 biopsy-proven malignancy and high suspicion by PET-CT, a second biopsy was deemed unnecessary for many patients. Therefore we cannot report what percentage of our patients had same or different histology to develop firm conclusions about outcomes with respect to this variable.Although our review contained only 10 patients and the median follow-up was only 18.5 months, the preliminary results indicate that there was no significant toxicity (Grade >3) in the treatment of bilateral MPLC using SBRT, delivered by an experienced center. SBRT may be a safe and potentially effective treatment of bilateral MPLC; however, larger studies and longer follow-up is still needed. IntroductionMultiple primary lung cancer (MPLC) has been described for many decades; however, its prevalence still remains largely unknown (1Rea F. Zuin A. Callegaro D. et al.Surgical results for multiple primary lung cancers.Eur J Cardiothorac Surg. 2001; 20: 489-495Crossref PubMed Scopus (60) Google Scholar, 2Antakli T. Schaefer R. Rutherford J. et al.Second primary lung cancer.Ann Thorac Surg. 1995; 59: 863-866Abstract Full Text PDF PubMed Scopus (172) Google Scholar, 3Tsunezuka Y. Matsumoto I. Tamura M. et al.The results of therapy for bilateral multiple primary lung cancers: 30 years experience in a single centre.Eur J Surg Oncol. 2004; 30: 781-785Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 4Nakata M. Sawada S. Yamashita M. et al.Surgical treatments for multiple primary adenocarcinoma of the lung.Ann Thorac Surg. 2004; 78: 1194-1199Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 5Aziz T.M. Saad R.A. Glasser J. et al.The management of second primary lung cancers A single centre experience in 15 years.Eur J Cardiothorac Surg. 2002; 21: 527-533Crossref PubMed Scopus (95) Google Scholar, 6Adebonojo S.A. Moritz D.M. Danby C. et al.The results of modern surgical therapy for multiple primary lung cancers.Chest. 1997; 112: 693-701Crossref PubMed Scopus (104) Google Scholar, 7Martini N. Melamed M.R. Multiple primary lung cancers.J Thorac Cardiovasc Surg. 1975; 70: 606-612PubMed Google Scholar). The risk of developing metachronous pulmonary lung cancers after surgical resection of early-stage lung cancer has been estimated at 2% to 3% per year (1Rea F. Zuin A. Callegaro D. et al.Surgical results for multiple primary lung cancers.Eur J Cardiothorac Surg. 2001; 20: 489-495Crossref PubMed Scopus (60) Google Scholar, 2Antakli T. Schaefer R. Rutherford J. et al.Second primary lung cancer.Ann Thorac Surg. 1995; 59: 863-866Abstract Full Text PDF PubMed Scopus (172) Google Scholar). Often times these patients have significant comorbidities that preclude bi-lobectomy or pneumonectomy and thus present physicians with treatment dilemmas.Beginning in 1999, a study of the use of stereotactically-targeted radiation therapy for the curative treatment of solitary early-stage non–small-cell lung cancer in patients who were unable to undergo curative surgery by virtue of medical comorbidities was undertaken at Indiana University. Since then we have completed a Phase I and Phase II study to define appropriate doses and confirm the safety of this technology. During the course of this study, 10 patients were found to have either multiple, or more specifically, bilateral, independent malignant pulmonary nodules at initial workup or subsequently in the course of their disease (8McGarry R.C. Papiez L. Williams M. et al.Stereotactic body radiation therapy of early-stage non–small-cell lung carcinoma: phase I study.Int J Radiat Oncol Biol Phys. 2005; 63: 1010-1015Abstract Full Text Full Text PDF PubMed Scopus (417) Google Scholar, 9Timmerman R. Papiez L. McGarry R.C. et al.Extracranial stereotactic radioablation: Results of a phase I study in medically inoperable stage I non-small cell lung cancer.Chest. 2003; 124: 1946-1955Crossref PubMed Scopus (590) Google Scholar). The criteria set by Martini and Melamed (7Martini N. Melamed M.R. Multiple primary lung cancers.J Thorac Cardiovasc Surg. 1975; 70: 606-612PubMed Google Scholar) or the modified version by Antakli (2Antakli T. Schaefer R. Rutherford J. et al.Second primary lung cancer.Ann Thorac Surg. 1995; 59: 863-866Abstract Full Text PDF PubMed Scopus (172) Google Scholar) were used to differentiate independently arising lung cancers from metastatic disease. The cancer in the majority of patients was deemed medically inoperable and patients had few options for further treatment. Therefore they elected to undergo stereotactic radiation therapy. In a review of the literature, there is data available on surgical outcomes of patients with resected multiple or bilateral primary lung cancers (1Rea F. Zuin A. Callegaro D. et al.Surgical results for multiple primary lung cancers.Eur J Cardiothorac Surg. 2001; 20: 489-495Crossref PubMed Scopus (60) Google Scholar, 3Tsunezuka Y. Matsumoto I. Tamura M. et al.The results of therapy for bilateral multiple primary lung cancers: 30 years experience in a single centre.Eur J Surg Oncol. 2004; 30: 781-785Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar, 4Nakata M. Sawada S. Yamashita M. et al.Surgical treatments for multiple primary adenocarcinoma of the lung.Ann Thorac Surg. 2004; 78: 1194-1199Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, 5Aziz T.M. Saad R.A. Glasser J. et al.The management of second primary lung cancers A single centre experience in 15 years.Eur J Cardiothorac Surg. 2002; 21: 527-533Crossref PubMed Scopus (95) Google Scholar, 6Adebonojo S.A. Moritz D.M. Danby C. et al.The results of modern surgical therapy for multiple primary lung cancers.Chest. 1997; 112: 693-701Crossref PubMed Scopus (104) Google Scholar); however there is virtually no published data on management alternatives or outcomes of patients with medically inoperable cancers.The purpose of this retrospective review is to evaluate the toxicity and disease control with stereotactic body radiation therapy (SBRT) for bilateral MPLC in the medically inoperable patient population.