1. Early Stage Lung Cancer Wake Forest Baptist Medical Center Radiation Oncology Department John T. Lucas Jr. MD, MSCR PGY2
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10. Surgery - Types - Sublobar Resection RJ Ginsberg, LV Rubinstein and Lung Cancer Study Group Ann Thorac Surg 1995;60:615-23 - Lobectomy vs. Sublobar for Early Stage NSCLC
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18. SBRT Dose/Fractionation Phase 1 Dose Finding Study 37 Stage 1 NSCLC Patients 1o Objective: Est DLT/MTD 8Gy x 3 to the 80% IDL 10Gy x 3 12Gy x 3 14Gy x 3 16Gy x 3 18Gy x 3 20Gy x 3 @ 14Gy stratified to escalate dose independently for T1 & T2 tumors
19. SBRT Dose/Fractionation - Didnt reach MTD - No diff in Tox b/n T1 or T2 - No heterogeneity correction - No significant cardiopulmonary toxicity - 87% Objective RR, 27% CR - 6 failures in patients all <18Gy/fx 8Gy x 3 to the 80% IDL 10Gy x 3 12Gy x 3 14Gy x 3 16Gy x 3 18Gy x 3 20Gy x 3
22. SBRT Dose/Fractionation 2 yr freedom from toxicity -Central: 54% -Peripheral: 83% - Only additional predictor of toxicity was size of GTV, with > 10 cc tumors showing greater toxicity than smaller GTVs. - G3/4 Toxicity events occurred a median of 7.6 mo after completion of SBRT.
24. SBRT Dose/Fractionation Prospective Cohort 27 Patients w/Central NSCLC (Recurrent (14) or Stage 1 (13) Median f/u of 17 mo - Prescribed dose of 40 Gy (n = 7) to the PTV - Escalated to 50 Gy (n = 20) in 4 consecutive days 1 patient experienced a brachial plexopathy w/20% of plexus recieving >40Gy LC was poor w/<50Gy~ 3/7 failed Not powered for any objectives, limited conclusions can be drawn - However 50Gy/4 fractions appears safe for central tumors - <50Gy is associated w/a higher failure rate
25. SBRT Dose/Fractionation Central Dose Question is currently being evaluated prospectively w/: RTOG 0813 Phase I/II Study of SBRT in Medically Inoperable Patients w/Centrally Located Stage I NSCLC Dose Escalation: 50Gy/5fx --> 52.5/5 --> 55/5 --> 57.5/5 --> 60Gy/5fx - Has high dose conformality index requirements that necessitate noncoplanar beam arrangement - OARs are limited to <105% of prescribed dose - Low and High Dose spillage are highly restrictive
BRIEF HISTORY OF early half of the 20th century, pneumonectomy was considered the only appropriate treatment of primary lung cancer. - Unacceptably high mortality rate associated with pneumonectomy (40%) at the time, lobectomy evolved as the treatment of choice for resectable peripheral cancers. Sublobar, sublobular, conservative, lesser, substandard or limited resections - First reported by Churchill and Belsey first reported segmentectomy for the treatment of Bronchiectasis in 1939. - Jensik and colleagues who first described its use for lung cancer resection in 1973. Segmentectomy: implies the removal of an anatomical unit. It requires the identification and dissection of the segmental bronchus and artery, which are sutured and segment and adjacent subsegments plus exploration of mediastinal and hilar lymph nodes, which are examined pathologically as intra-operative frozen sections to confirm pathological node (N)0 status Sleeve segmentectomies: the segmental bronchus is not incised at its origin, but it is removed with part of the lobar bronchus, which is then reconstructed with an end-to-end anastomosis. This is indicated when the tumour is too close to the origin of the segmental bronchus, in order to avoid a lobectomy Wedge/Atypical resection is the removal of part of the lung regardless of its anatomical boundaries. - Can be part of one segment or a portion of lung parenchyma comprising two or more neighbouring segments.
BRIEF HISTORY OF early half of the 20th century, pneumonectomy was considered the only appropriate treatment of primary lung cancer. - Unacceptably high mortality rate associated with pneumonectomy (40%) at the time, lobectomy evolved as the treatment of choice for resectable peripheral cancers. Sublobar, sublobular, conservative, lesser, substandard or limited resections - First reported by Churchill and Belsey first reported segmentectomy for the treatment of Bronchiectasis in 1939. - Jensik and colleagues who first described its use for lung cancer resection in 1973. Segmentectomy: implies the removal of an anatomical unit. It requires the identification and dissection of the segmental bronchus and artery, which are sutured and segment and adjacent subsegments plus exploration of mediastinal and hilar lymph nodes, which are examined pathologically as intra-operative frozen sections to confirm pathological node (N)0 status Sleeve segmentectomies: the segmental bronchus is not incised at its origin, but it is removed with part of the lobar bronchus, which is then reconstructed with an end-to-end anastomosis. This is indicated when the tumour is too close to the origin of the segmental bronchus, in order to avoid a lobectomy Wedge/Atypical resection is the removal of part of the lung regardless of its anatomical boundaries. - Can be part of one segment or a portion of lung parenchyma comprising two or more neighbouring segments.
As expected, QOL decreased significantly after surgery in both groups. The lowest QOL scores were observed immediately after discharge from the hospital, and were followed by a period of slow recovery. In contrast to other reports, NEITHER group experienced a return to preoperative QOL, even after 24 months. Comparison of QOL after lobectomy and pneumonectomy for coughing (top, A), pain (center, B), and dyspnoea (bottom, C). QOL of an age-matched reference group is indicated as a dotted line. *p < 0.05, **p < 0.001 (only available for EORTC QLQ-C30).
As expected, QOL decreased significantly after surgery in both groups. The lowest QOL scores were observed immediately after discharge from the hospital, and were followed by a period of slow recovery. In contrast to other reports, NEITHER group experienced a return to preoperative QOL, even after 24 months. Comparison of QOL after lobectomy and pneumonectomy for coughing (top, A), pain (center, B), and dyspnoea (bottom, C). QOL of an age-matched reference group is indicated as a dotted line. *p < 0.05, **p < 0.001 (only available for EORTC QLQ-C30).
**Subsequent studies reported the usefulness of segmentectomy as a compromise operation in selected, poor-risk patients. Notably, in 1985, Errett et reported a 17-year experience in which 197 patients underwent wedge resection or lobectomy for bronchogenic carcinoma and demonstrated a 2-year survival of 72% versus 74%, as well as a 6-year survival of 69% versus 75%, a difference that was not statistically significant. Importantly, patients who underwent wedge resection had significantly impaired cardiopulmonary function and were not candidates for lobectomy. Despite these early studies suggesting equivalency in survival between sublobar and lobar resection for lung cancer, the higher technical complexity of performing a segmentectomy, particularly in dissecting along the intersegmental plane which may increase the potential for a prolonged air leak, was of great concern to many surgeons. On the other hand, with a limited resection and further preservation of lung volume, perioperative morbidity and mortality can potentially be reduced, and opportunities for additional lung resection in the future could be maintained should the patient develop a recurrence or a second cancer. _____________________ Background Although lobectomy is the procedure of preference for patients with peripheral, clinical Stage I bronchogenic carcinomas, wedge resection of the tumor may be a satisfactory alternative in poor-risk patients. Methods -1965 & 1982, 197 patients with peripheral bronchogenic carcinomas were operated upon. - Clinical staging was established by radiography, bronchoscopy, and mediastinoscopy. - 97 underwent lobectomies & 100 had wedge resections. - The decision to perform the wedge resection was made preoperatively in the majority of cases based on the assessment of operative risks. Results - Compared to lobectomy patients, those who had wedge resections were older (70.3 +/- 0.5 versus 64.9 +/- 0.5 years, p less than 0.001) and had a lower 1 second forced expiratory volume (1.56 +/- 0.03 versus 1.94 +/- 0.03 ml, p less than 0.001), a lower arterial oxygen tension (70.5 +/- 1.1 versus 75.6 +/- 1.2 mm Hg, p less than 0.01), and a higher arterial carbon dioxide tension (41.7 +/- 0.6 versus 38.7 +/- 0.3 mm Hg, p less than 0.001). - Despite their compromised preoperative respiratory functional status, the wedge resection group had a 30 day operative mortality (3% versus 2.1%) and morbidity comparable to those of the lobectomy group. - Actuarial life-table analysis indicates the cumulative survival rate at 2 years after operation to be virtually identical between wedge and lobectomy groups (72% versus 74%), and even at 6 years the differences in survival rates (69% versus 75%) were not statistically significant. Conclusion We conclude, therefore, that by performing wedge resections in selected poor-risk patients, one may reduce the operative mortality and morbidity to an acceptable range without seriously compromising their long-term survival.
Background.: It has been reported that limited resection (segment or wedge) is equivalent to lobectomy in the management of early stage (T1–2 N0) non-small cell lung cancer. Methods.: A prospective, multiinstitutional randomized trial was instituted comparing limited resection with lobectomy for patients with peripheral T1 N0 non-small cell lung cancer documented at operation. Analysis included locoregional and distant recurrence rates, 5-year survival rates, perioperative morbidity and mortality, and late pulmonary function assessment. Results: 276 patients randomized 247 patients eligible - no significant differences for all stratification variables, selected prognostic factors, perioperative morbidity, mortality, or late pulmonary function. - limited resection, there was an observed 75% increase in recurrence rates ( p = 0.02, one-sided) attributable to an observed tripling of the local recurrence rate ( p = 0.008 two-sided), an observed 30% increase in overall death rate ( p = 0.08, one-sided), and an observed 50% increase in death with cancer rate ( p = 0.09, one-sided) compared to patients undergoing lobectomy ( p = 0.10, one-sided was the predefined threshold for statistical significance for this equivalency study). Conclusions.: Compared with lobectomy, limited pulmonary resection does not confer improved perioperative morbidity, mortality, or late postoperative pulmonary function. Because of the higher death rate and locoregional recurrence rate associated with limited resection, lobectomy still must be considered the surgical procedure of choice for patients with peripheral T1 N0 non-small celllung cancer.
What about QOL w/sublobar No SS diff in # of postoperative complications or postoperative mortality - lobectomy group -- 6 patients developed Respiratory Failure requiring postoperative ventilation for >24 hr -- No patient in the limited resection group required ventilatory assitance. 3 postoperative deaths among the 276 patients. -- 2 in the |obectomy -- 1 in the sublobar **SS diff in FEV1 at 6&12 mo -- interestingly NS diff in FVC
RFA is a thermal energy delivery system that applies an alternating current supplied by a radiofrequency energy generator, delivered through a needle electrode. The needle electrode is introduced percutaneously under CT guidance into the tumor, and multiple tines are deployed within the tumor This allows for maximal distribution of energy, and the alternating current generates ionic agitation, creating heat that can reach 908C. This leads to coagulative necrosis and tissue destruction in the precise area of the probe.
OBJECTIVE. This study retrospectively evaluates complications after lung radiofrequency ablation (RFA). MATERIALS AND METHODS. Complications were assessed for each RFA session in 420 consecutive patients with 1403 lung tumors who underwent 1000 RFA sessions with a cool-tip RFA system. A major complication was defined as a grade 3 or 4 adverse event. Risk factors affecting frequent major complications that occurred with an incidence of 1% or more were detected using multivariate analysis
OBJECTIVE. This study retrospectively evaluates complications after lung radiofrequency ablation (RFA). MATERIALS AND METHODS. Complications were assessed for each RFA session in 420 consecutive patients with 1403 lung tumors who underwent 1000 RFA sessions with a cool-tip RFA system. A major complication was defined as a grade 3 or 4 adverse event. Risk factors affecting frequent major complications that occurred with an incidence of 1% or more were detected using multivariate analysis. RESULTS. Four deaths (0.4% [4/1000]) related to RFA procedures occurred. Three patients died of interstitial pneumonia. The other patient died of hemothorax. The major complication rate was 9.8% (98/1000). Frequent major complications were aseptic pleuritis (2.3% [23/1000]), pneumonia (1.8% [18/1000]), lung abscess (1.6% [16/1000]), bleeding requiring blood transfusion (1.6% [16/1000]), pneumothorax requiring pleural sclerosis (1.6% [16/1000]), followed by bronchopleural fistula (0.4% [4/1000]), brachial nerve injury (0.3% [3/1000]), tumor seeding (0.1% [1/1000]), and diaphragm injury (0.1% [1/1000]). Puncture number ( p < 0.02) and previous systemic chemotherapy ( p < 0.05) were significant risk factors for aseptic pleuritis. Previous external beam radiotherapy ( p < 0.001) and age ( p < 0.02) were significant risk factors for pneumonia, as were emphysema ( p < 0.02) for lung abscess, and serum platelet count ( p < 0.002) and tumor size ( p < 0.02) for bleeding. Emphysema ( p < 0.02) was a significant risk factor for pneumothorax requiring pleural sclerosis. CONCLUSION. Lung RFA is a relatively safe procedure, but it can be fatal. Risk factors found in this study will help to stratify high-risk patients.
Abstract INTRODUCTION: We set out to investigate a new therapy akin to brain radiosurgery called extracranial stereotactic radioablation (ESR) in a phase I trial. PATIENTS AND METHODS: -cT1 or T2 (tumor size, < or = 7 cm) N0M0 biopsy confirmed NSCLC -All patients had comorbid medical problems that precluded thoracotomy. -The median age was 75 years, and the median Karnofsky performance status was 80. -ESR was administered in three separate fractions over 2 weeks. Three to five patients were treated within each dose cohort starting at 800 cGy per fraction (total, 2,400 cGy) followed by successive dose escalations of 200 cGy per fraction (total increase per cohort, 600 cGy). Waiting periods occurred between dose cohorts to observe toxicity. Patients with T1 vs T2 tumors underwent separate independent dose escalations.
RESULTS: A total of 37 patients were enrolled since February 2000. 1 ptnt experienced G3 pneumonitis 1 patient G3 hypoxia No appreciable decline in cardiopulmonary function as measured by symptoms, physical examination, need for O2 supplementation, PFTs, ABG, or regular chest imaging. Both T-stage groups ultimately reached and tolerated 2,000 cGy per fraction for three fractions (total, 6,000 cGy). The MTD for this therapy in either T-stage group has yet to be reached. Tumors responded to treatment in 87% of patients (complete response, 27%). After a median follow-up period of 15.2 months, six patients experienced local failure, all of whom had received doses of < 1,800 cGy per fraction. CONCLUSIONS: Very high radiation dose treatments were tolerated in this population of medically inoperable patients with stage I NSCLC using ESR techniques.
Introduction: Hypofractionated stereotactic radiotherapy (HypoFXSRT) has recently been used for the treatment of small lung tumors. We retrospectively analyzed the treatment outcome of HypoFXSRT for stage I non-small cell lung cancer (NSCLC) treated in a Japanese multi-institutional study. Methods: This is a retrospective study to review 257 patients with stage I NSCLC median age, 74 years: 164 T1N0M0, 93 T2N0M0 Stereotactic 3D tx using noncoplanar dynamic arcs or multiple static ports. Tx: total dose of 18 to 75 Gy at the isocenter in one to 22 fractions. Median calculated biological effective dose (BED) was 111 Gy (range, 57–180 Gy) based on [alpha]/[beta] = 10. Results: Median follow-up 38 months G2 pulmonary in 14 ptnts 5.4% Local progression in 36 ptnts 14.0% LR rate 8.4% for a BED >100 Gy compared w/42.9% for less than 100 Gy (p < 0.001). **assumes an early a/b of 10 5 yr OS of medically operable 70.8% if >100Gy BED 30.2% if < 100 Gy (p < 0.05).
Purpose Surgical resection is standard therapy in stage I non–small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population. Patients and Methods Eligible patients included clinically staged T1 or T2 ( 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks. Results 100% of 70 patients enrolled completed therapy - Median follow-up was 17.5 months. - 3 mo major RR was 60%. - Kaplan-Meier LC @ 2 years was 95%. - 28 patients have died as a result of cancer (n = 5), - Treatment (n = 6) - Comorbid illnesses (n = 17) - Median OS was 32.6 mo - 2 yr OS was 54.7%. Purpose Surgical resection is standard therapy in stage I non–small-cell lung cancer (NSCLC); however, many patients are inoperable due to comorbid diseases. Building on a previously reported phase I trial, we carried out a prospective phase II trial using stereotactic body radiation therapy (SBRT) in this population. Patients and Methods Eligible patients included clinically staged T1 or T2 ( 7 cm), N0, M0, biopsy-confirmed NSCLC. All patients had comorbid medical problems that precluded lobectomy. SBRT treatment dose was 60 to 66 Gy total in three fractions during 1 to 2 weeks. Results 100% of 70 patients enrolled completed therapy - Median follow-up was 17.5 months. - 3 mo major RR was 60%. - Kaplan-Meier LC @ 2 years was 95%. - 28 patients have died as a result of cancer (n = 5), - Treatment (n = 6) - Comorbid illnesses (n = 17) - Median OS was 32.6 mo - 2 yr OS was 54.7%.
The study was particularly instructive in terms of local toxicity: 8 patients were deemed by the data safety monitoring board to have grade 3 or 4 adverse events resulting from SBRT; - the adverse events were primarily respiratory (decline in pulmonary function, PNA, pleural effusion, apnea) and/or skin reaction; occurred a median of 7.6 mo after completion of SBRT. Six patients may potentially have had grade 5 (i.e., fatal) toxicity. In five patients, these grade 5 adverse events were respiratory: - one fatal hemoptysis (associated with a local recurrence) - four infectious pneumonias; - Sixth patient died of complications from a pericardial effusion. These deaths occurred a median of 10.4 months after SBRT (range 0.6-19.5 mo). Tumor location was a strong predictor of toxicity, with hilar or pericentral tumors showing an 11-fold increased risk in grade 3-5 adverse events when compared to more peripheral tumors (p=0.004). 2-year freedom from severe adverse events was 54% for these central tumors, as compared to 83% for the peripheral tumors, defined as outside the “zone of the proximal bronchial tree”, which is a 2 cm radius around the main tracheo-bronchial tree: trachea; left and right main stem bronchi; right upper, middle, and lower lobe bronchus; and left upper, lingular, and lower lobe bronchus. if solve for r w/vol=10cm^3 4/3*pi*r^3 r= 2.28cm d=4.56 cm
Defined as outside the “zone of the proximal bronchial tree”, which is a 2 cm radius around the main tracheo-bronchial tree: trachea; left and right main stem bronchi; right upper, middle, and lower lobe bronchus; and left upper, lingular, and lower lobe bronchus. strong as tumor location, was the size of gross tumor volume (GTV), with > 10 cc tumors showing greater toxicity than smaller GTVs.
Purpose To evaluate the efficacy & adverse effects of image-guided SBRT in centrally/superiorly located NSCLC Materials and Methods -SBRT to 27 patients -13 w/Stage I -14 w/isolated recurrent NSCLC A central/superior location was defined as being within 2 cm of the bronchial tree, major vessels, esophagus, heart, trachea, pericardium, brachial plexus, or vertebral body, but 1 cm away from the spinal canal. 4D CT planning & daily CBCT - Prescribed dose of 40 Gy (n = 7) to the PTV - Escalated to 50 Gy (n = 20) in 4 consecutive days. Results -median f/up of 17 mo (range, 6–40 months) -Crude local control @ the tx'd site was 100% using 50 Gy. - 3/7 patients tx'd w/40Gy had LR - Of those w/Stage I disease - 7.7% Mediastinal failure - 15.4% Distant metastases Recurrent disease 21.4% Mediastinal failure 35.7% Distant failure G2 pneumonitis 28.6% with recurrent disease 11.1% developed Grade 2-3 dermatitis and chest wall pain. 1 ptnt w/brachial plexus neuropathy. No esophagitis was noted in any patient. Conclusions Image-guided SBRT using 50 Gy delivered in four fractions is feasible and resulted in excellent local control.
Purpose To evaluate the efficacy & adverse effects of image-guided SBRT in centrally/superiorly located NSCLC Materials and Methods -SBRT to 27 patients -13 w/Stage I -14 w/isolated recurrent NSCLC A central/superior location was defined as being within 2 cm of the bronchial tree, major vessels, esophagus, heart, trachea, pericardium, brachial plexus, or vertebral body, but 1 cm away from the spinal canal. 4D CT planning & daily CBCT - Prescribed dose of 40 Gy (n = 7) to the PTV - Escalated to 50 Gy (n = 20) in 4 consecutive days. Results -median f/up of 17 mo (range, 6–40 months) -Crude local control @ the tx'd site was 100% using 50 Gy. - 3/7 patients tx'd w/40Gy had LR - Of those w/Stage I disease - 7.7% Mediastinal failure - 15.4% Distant metastases Recurrent disease 21.4% Mediastinal failure 35.7% Distant failure G2 pneumonitis 28.6% with recurrent disease 11.1% developed Grade 2-3 dermatitis and chest wall pain. 1 ptnt w/brachial plexus neuropathy. No esophagitis was noted in any patient. Conclusions Image-guided SBRT using 50 Gy delivered in four fractions is feasible and resulted in excellent local control.
Context Patients with early stage but medically inoperable lung cancer have a poor rate of primary tumor control (30%-40%) and a high rate of mortality (3-year survival, 20%-35%) with current management. Objective: To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high-risk population of patients with early stage but medically inoperable lung cancer. Design, Setting, and Patients Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1-T2N0M0 non–small cell tumors (measuring <5 cm in diameter) and medical conditions precluding surgical treatment. EXCLUDED CENTRAL TUMORS (Proximal Zone) The prescription dose was 18 Gy per fraction × 3 fractions (54 Gy total) with entire treatment lasting between 1½ and 2 weeks. The study opened May 26, 2004, and closed October 13, 2006; data were analyzed through August 31, 2009. Main Outcome Measures The primary end point was 2-year actuarial primary tumor control; secondary end points were disease-free survival (ie, primary tumor, involved lobe, regional, and disseminated recurrence), treatment-related toxicity, and overall survival.
Results -59 patients accrued -55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors) -Median f/u 34.4 mo (range, 4.8-49.9 months). 1o tumor failure was based on meeting both criteria: (1) local enlargement defined as at least a 20% increase in the longest diameter of the gross tumor volume per CT scan (2) evidence of tumor viability. Tumor viability could be affirmed by either demonstrating PET imaging with uptake of a similar intensity as the pretreatment staging PET, or by repeat biopsy-confirming carcinoma. Primary tumor failure included marginal failures occurring within 1 cm of the planning target vol- ume (1.5-2.0 cm from the gross tumor volume). Failure beyond the primary tumor but within the involved lobe was collected separately from dissemi- nated failure within uninvolved lobes. 1o tumor failure= marginal failures occurring w/in 1 cm of PTV (1.5-2.0 cm from the GTV Local failure= 1o tumor & involved lobe failure Local control= absence of local failure Regional Failure: 1o, involved lobe, hilum, &/or mediastinum. Disseminated Recurrence: failure beyond the local & regional sites (can include contralteral lobe) - 1 patient had a 1o Failure - Est 3yr LC rate 97.6% (95% CI 84.3%-99.7%) - 3 patients had recurrence w/in the involved lobe - 3 yr 1o tumor & involved lobe (local) control rate was 90.6% (95%CI,76.0%-96.5%) - 2 ptnts w/regional failure - Local-regional control rate was 87.2% (95% CI, 71.0%-94.7%) - 11 patients exp dissem recurrence - 3yr rate of disseminated failure was 22.1% (95% CI, 12.3%-37.8%). - 3yr DFS 48.3% (95% CI, 34.4%-60.8%) - 3 yr OS 55.8% (95% CI, 41.6%-67.9%) - Median OS 48.1 mo (95% CI, 29.6- not reached).
Results -59 patients accrued -55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors) -Median f/u 34.4 mo (range, 4.8-49.9 months). 1o tumor failure= marginal failures occurring w/in 1 cm of PTV (1.5-2.0 cm from the GTV Local failure= 1o tumor & involved lobe failure Local control= absence of local failure Regional Failure: 1o, involved lobe, hilum, &/or mediastinum. Disseminated Recurrence: failure beyond the local & regional sites (can include contralteral lobe) - 1 patient had a 1o Failure - Est 3yr LC rate 97.6% (95% CI 84.3%-99.7%) - 3 patients had recurrence w/in the involved lobe - 3 yr 1o tumor & involved lobe (local) control rate was 90.6% (95%CI,76.0%-96.5%) - 2 ptnts w/regional failure - Local-regional control rate was 87.2% (95% CI, 71.0%-94.7%) - 11 patients exp dissem recurrence - 3yr rate of disseminated failure was 22.1% (95% CI, 12.3%-37.8%). - 3yr DFS 48.3% (95% CI, 34.4%-60.8%) - 3 yr OS 55.8% (95% CI, 41.6%-67.9%) - Median OS 48.1 mo (95% CI, 29.6- not reached).
Results: Median f/u of 38.7 mo - 1 (2%) G4 pulmonary - 7 (13%) G3 pulmonary/upper respiratory adverse events 2/2 protocol - 2/7 reported PFT decrease - 1/7 reported cough/dyspnea - 1 reported hypoxia - 1 reported pneumonitis - 1 reported cough - 1 patient reported PNX - 1 G3 dermatitis - 1 G3 syncope reported as related to protocol treatment. - No treatment related deaths have been reported. Comparison
48Gy/4fx vs. 34Gy/1 If a/b 10 for early then 48Gy/4fx BED - Early 105 BED - Late 240 34Gy/1 BED - Early 149Gy BED - Late 419Gy
48Gy/4fx vs. 34Gy/1 If a/b 10 for early then 48Gy/4fx BED - Early 105 BED - Late 240 34Gy/1 BED - Early 149Gy BED - Late 419Gy
Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy SBRT . The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy SBRT . The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures.
PET- noninvasive and highly sensitivie and thus excellent at ruling out disease - However, will miss disease about 14% of the time - Negative results from a sensitive test = rule out - Positive result from a specific test = rule in Mediastinscopy- Invasive w/increased sensitivity and sensitivity so useful for both ruling out and ruling in disease - However will still miss 7% of occult disease Even w/most sensitivie means of detecting disease, will miss 7-14% of occult disease resulting in nodal failures - So for every 10 PET scan, you will likely miss 1 presentation of occult disease unless staged operatively and w/imaging. - If we assume that each event are not mutually exclusion then the combined probability of obtaining a: - FN is 1- sensitivity= 7014% - If PET and Med = 1% - If PET and EBUS = 2-4% So for every patient staged at Wake - likely 2-4% chance of missing occult disease as we most commonly complete PET and EBUS (w/limited sampling)
PET- noninvasive and highly sensitivie and thus excellent at ruling out disease - However, will miss disease about 14% of the time - Negative results from a sensitive test = rule out - Positive result from a specific test = rule in Mediastinscopy- Invasive w/increased sensitivity and sensitivity so useful for both ruling out and ruling in disease - However will still miss 7% of occult disease Even w/most sensitivie means of detecting disease, will miss 7-14% of occult disease resulting in nodal failures - So for every 10 PET scan, you will likely miss 1 presentation of occult disease unless staged operatively and w/imaging. - If we assume that each event are not mutually exclusion then the combined probability of obtaining a: - FN is 1- sensitivity= 7014% - If PET and Med = 1% - If PET and EBUS = 2-4% So for every patient staged at Wake - likely 2-4% chance of missing occult disease as we most commonly complete PET and EBUS (w/limited sampling)
BACKGROUND: To assess for variables predicting pulmonary function test (PFT) changes after SBRT for medically inoperable stage I lung cancer. METHODS: -92 consecutive patients undergoing SBRT for stage I lung cancer between February 2004 and August 2007. -A total of 102 lesions were treated using prescriptions of 20 Gy x 3 (n = 40), 10 Gy x 5 (n = 56), and 5 Gy x 10 (n = 6). -Institutional practice was 10 Gy x 5 before March 1, 2006 before changing to 20 Gy x 3 to conform to RTOG 0236 unless otherwise dictated clinically. RESULTS: - Median pretreatment forced expiratory volume at 1 second (FEV1) was 1.21 liter (50% of predicted) and median diffusion capacity to carbon monoxide (DLCO) was 56.5. **There was no significant overall change in PFT's after SBRT. **Individual patients experienced both substantial improvements and declines (10% declined at least 14% predicted FEV1% and 19% predicted DLCO). -The mean change in FEV1 was -0.05 liter (range, -0.98 to +1.29 liter; p = 0.22) representing -1.88% predicted baseline FEV1 (range, -33 to + 43%; p = 0.62). -DLCO declined 2.59% of predicted (range, -37 to +33%; p = 0.27). ** Conformality index, V5 and V10 were associated with individual patient changes in FEV1% (p = 0.033, p = 0.0036, p = 0.025, respectively), however, correlations were small and overall treatment dose did not predict for changes (p = 0.95). -There was no significant difference in FEV1 (p = 0.55) or FEV1% (p = 0.37) changes for central versus peripheral locations. -No factors predicted for individual changes in DLCO. -Patients with FEV1% below the median of the study population had significantly longer overall survival (p = 0.0065). -Although patients dying of cardiac disease died earlier than those dying of other causes, FEV1% below median was not associated with a lower risk of dying of cardiac disease or with lower Charlson comorbidity index. CONCLUSIONS: (1) SBRT was well tolerated and PFT changes were minimal.
BACKGROUND: To assess for variables predicting pulmonary function test (PFT) changes after SBRT for medically inoperable stage I lung cancer. METHODS: -92 consecutive patients undergoing SBRT for stage I lung cancer between February 2004 and August 2007. -A total of 102 lesions were treated using prescriptions of 20 Gy x 3 (n = 40), 10 Gy x 5 (n = 56), and 5 Gy x 10 (n = 6). -Institutional practice was 10 Gy x 5 before March 1, 2006 before changing to 20 Gy x 3 to conform to RTOG 0236 unless otherwise dictated clinically. RESULTS: - Median pretreatment forced expiratory volume at 1 second (FEV1) was 1.21 liter (50% of predicted) and median diffusion capacity to carbon monoxide (DLCO) was 56.5. **There was no significant overall change in PFT's after SBRT. **Individual patients experienced both substantial improvements and declines (10% declined at least 14% predicted FEV1% and 19% predicted DLCO). -The mean change in FEV1 was -0.05 liter (range, -0.98 to +1.29 liter; p = 0.22) representing -1.88% predicted baseline FEV1 (range, -33 to + 43%; p = 0.62). -DLCO declined 2.59% of predicted (range, -37 to +33%; p = 0.27). ** Conformality index, V5 and V10 were associated with individual patient changes in FEV1% (p = 0.033, p = 0.0036, p = 0.025, respectively), however, correlations were small and overall treatment dose did not predict for changes (p = 0.95). -There was no significant difference in FEV1 (p = 0.55) or FEV1% (p = 0.37) changes for central versus peripheral locations. -No factors predicted for individual changes in DLCO. -Patients with FEV1% below the median of the study population had significantly longer overall survival (p = 0.0065). -Although patients dying of cardiac disease died earlier than those dying of other causes, FEV1% below median was not associated with a lower risk of dying of cardiac disease or with lower Charlson comorbidity index. CONCLUSIONS: (1) SBRT was well tolerated and PFT changes were minimal.
PET- noninvasive and highly sensitivie and thus excellent at ruling out disease - However, will miss disease about 14% of the time - Negative results from a sensitive test = rule out - Positive result from a specific test = rule in Mediastinscopy- Invasive w/increased sensitivity and sensitivity so useful for both ruling out and ruling in disease - However will still miss 7% of occult disease Even w/most sensitivie means of detecting disease, will miss 7-14% of occult disease resulting in nodal failures - So for every 10 PET scan, you will likely miss 1 presentation of occult disease unless staged operatively and w/imaging. - If we assume that each event are not mutually exclusion then the combined probability of obtaining a: - FN is 1- sensitivity= 7014% - If PET and Med = 1% - If PET and EBUS = 2-4% So for every patient staged at Wake - likely 2-4% chance of missing occult disease as we most commonly complete PET and EBUS (w/limited sampling)
Purpose: Routine assessment was made of tumor metabolic activity as measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in Stage I non–small-cell lung cancer (NSCLC). This report describes PET correlates prospectively collected after stereotactic body radiotherapy (SBRT) for patients with medically inoperable NSCLC . Methods and Materials: 14 consecutive patients with medically inoperable Stage I NSCLC were enrolled . All patients received SBRT to 60–66 Gy in three fractions. Patients underwent serial planned FDG-PET/computed tomography fusion imaging before SBRT and at 2, 26, and 52 weeks after SBRT. Results: With median follow-up of 30.2 months , no patients experienced local failure. One patient developed regional failure, 1 developed distant failure, and 1 developed a second primary. The median tumor maximum standardized uptake value (SUVmax ) before SBRT was 8.70. The median SUVmax values at 2, 26, and 52 weeks after SBRT were 6.04, 2.80, and 3.58, respectively. Patients with low pre-SBRT SUV were more likely to experience initial 2-week rises in SUV, whereas patients with high pre-SBRT SUV commonly had SUV declines 2 weeks after treatment (p = 0.036). Six of 13 patients had primary tumor SUVmax >3.5 at 12 months after SBRT but remained without evidence of local disease failure on further follow-up. Conclusions: A substantial proportion of patients may have moderately elevated FDG-PET SUVmax at 12 months without evidence of local failure on further follow-up. Thus, slightly elevated PET SUVmax should not be considered a surrogate for local treatment failure . Our data do not support routine serial FDG-PET/computed tomography for follow-up of patients receiving SBRT for Stage I NSCLC. Fig. 1. Maximum standardized uptake volume (SUVmax) over time. The SUVmax of the 14 study patients at the time of their positron emission tomography/computed tomography (SBRT) scans before and after stereotactic body radiation therapy is graphed. At 12months after SBRT, many patients still had SUVmax values of 3.5 or above, despite a lack of local failure seen on extended follow-up.
PURPOSE: The aim of this study was to assess the outcomes of patients treated with stereotactic body radiation therapy (SBRT) in patients with primary, recurrent, or metastatic lung lesions, with a focus on positron emission tomography (PET)/computed tomography (CT)-based management . PATIENTS AND METHODS: Fifty-one patients with primary stage I non-small-cell lung cancer (NSCLC; n = 26), recurrent lung cancer after definitive treatment (n = 12), or solitary lung metastases (n = 13) were treated with SBRT between 2005 and 2007. Patients were treated with the CyberKnife Robotic Radiosurgery System with Synchrony respiratory tracking. A dose of 60 Gy was delivered in 3 fractions. All patients had CT or PET/CT performed at approximately 3-month intervals after treatment. RESULTS: The median follow-up was 12 months . Local control at median follow-up was 85% in patients with stage I NSCLC, 92% in patients with recurrent lung cancer, and 62% in the patients with solitary lung metastasis. Analysis of the 28 patients with pre- and post-treatment PET/CT scans demonstrated that those with stable disease (n = 4) had a mean standardized uptake value (SUV) decrease of 28%, partial responders (n = 11) had a decrease of 48%, and patients with a complete response (n = 11) had a decrease of 94%. Patients with progressive disease (n = 2) had an SUV decrease of only 0.4%. Only 2 patients (7%) who had reduced fluorodeoxyglucose avidity later progressed locally . No correlations were found between pretreatment SUV and tumor response, disease progression, or survival . Overall 1-year survival rates were 81%, 67%, and 85% among the patients with primary NSCLC, recurrent lung cancer, and solitary lung metastases, respectively. CONCLUSION: Stereotactic body radiation therapy with CyberKnife is an effective treatment for patients with medically inoperable recurrent or metastatic lung cancer. Positron emission tomography/CT is valuable in staging, planning, and evaluating treatment response and might predict long-term outcome.
The rate of hilar/mediastinal lymph node involvement found pathologically after surgery, despite a negative staging PET = 13% to 32% PET-only staged patients treated with SBRT, however, show such failure to be only 4% to 10%, despite careful assessments for recurrence with follow-up imaging. Why? Grills et al speculate that this may result from low-dose radiation spillage to regional lymph nodes; - Other speculate there may be an immune “vaccination” effect caused by exposing tumor antigens after ablative radiation. Target Population -prior trials were slow to accrue either 2/2 difficulty in comparable less invasive surgery or patient desire for choice.
Purpose To compare outcomes between lung stereotactic radiotherapy (SBRT) and wedge resection for stage I non–small-cell lung cancer (NSCLC). Patients and Methods One hundred twenty-four patients with T1-2N0 NSCLC underwent wedge resection (n = 69) or image-guided lung SBRT (n = 58) from February 2003 through August 2008. All were ineligible for anatomic lobectomy; of those receiving SBRT, 95% were medically inoperable, with 5% refusing surgery. Mean forced expiratory volume in 1 second and diffusing capacity of lung for carbon monoxide were 1.39 L and 12.0 mL/min/mmHg for wedge versus 1.31 L and 10.14 mL/min/mmHg for SBRT (P = not significant). Mean Charlson comorbidity index and median age were 3 and 74 years for wedge versus 4 and 78 years for SBRT (P < .01, P = .04). SBRT was volumetrically prescribed as 48 (T1) or 60 (T2) Gy in four to five fractions. Results Median potential follow-up is 2.5 years. At 30 months, no significant differences were identified in regional recurrence (RR), locoregional recurrence (LRR), distant metastasis (DM), or freedom from any failure (FFF) between the two groups (P > .16). SBRT reduced the risk of local recurrence (LR), 4% versus 20% for wedge (P = .07). Overall survival (OS) was higher with wedge but cause-specific survival (CSS) was identical. Results excluding synchronous primaries, nonbiopsied tumors, or pathologic T4 disease (wedge satellite lesion) showed reduced LR (5% v 24%, P = .05), RR (0% v 18%, P = .07), and LRR (5% v 29%, P = .03) with SBRT. There were no differences in DM, FFF, or CSS, but OS was higher with wedge. Conclusion Both lung SBRT and wedge resection are reasonable treatment options for stage I NSCLC patients ineligible for anatomic lobectomy. SBRT reduced LR, RR, and LRR. In this nonrandomized population of patients selected for surgery versus SBRT (medically inoperable) at physician discretion, OS was higher in surgical patients. SBRT and surgery, however, had identical CSS.
- Over the last decade, many studies have emerged suggesting equivalency between sublobar and lobar resection for the treatment of peripheral, early-stage NSCLC. - Many of these recent contributions emanate from investigators in Japan, where CT screening programs have been in place to detect lung cancer for over 10 years. - Several of these groups have demonstrated comparable outcomes using sublobar resection as primary treatment for lung cancer, even in good-risk patients - It is important to note that, despite the favorable outcomes seen among several Japanese reports, similar results may not necessarily be applicable to Western studies. ---? higher incidence of more indolent lung cancers such as bronchoalveolar carcinoma, which is more likely to have improved survival at early stages of disease
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