NCI CANCERLIT^® Search: Radiation, Surgery for Non-small Cell Lung Cancer - September 2001

Last Modified: November 1, 2001

Quality of life assessment in advanced non-small-cell lung cancer patients undergoing an accelerated radiotherapy regimen: report of ECOG study 4593. Eastern Cooperative Oncology Group.
Do patients with nonmetastatic non-small cell lung cancer demonstrate altered resting energy expenditure?
Predictors of lymph node and intrapulmonary metastasis in clinical stage IA non-small cell lung carcinoma.
Telescope anastomosis in bronchial sleeve resections with high-caliber mismatch.
[Standards, Options and Recommendations for the management of stage I or II primary bronchial cancers treated exclusively with radiotherapy]
[Less invasive treatment for lung carcinoma]
[Surgical treatment of non-small cell lung cancer with mediastinal node invasion. A retrospective study]
Appropriate surgical treatment of resectable non-small-cell lung cancer.
[Immunomorphology of lymph nodes and prognosis in lung cancer]
[Surgery for non-small cell lung cancer based on the T factor]
[Reevaluation of the surgical indications for lung cancer based on the N factor]
[Wedge resection for lung cancer]
[Video-assisted thoracoscopic surgery lobectomy for lung carcinoma]
[Reevaluation of the surgical indications for non-small cell lung cancer based on the results of postoperative treatment]
Synchronous chemoradiation for squamous carcinomas. This treatment is not gold standard for lung cancer.
F-18 fluorodeoxyglucose positron emission tomography staging in radical radiotherapy candidates with nonsmall cell lung carcinoma: powerful correlation with survival and high impact on treatment.
Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation.
Radiotherapy for inoperable lung cancer.
Long-term survival in patients with non-small cell lung cancer treated with palliative radiotherapy.
Assessment of lung cancer response after nonoperative therapy: tumor diameter, bidimensional product, and volume. A serial CT scan-based study.

CancerMail from the National Cancer Institute

1
UI - 21376173
AU - Auchter RM; Scholtens D; Adak S; Wagner H; Cella DF; Mehta MP
TI - Quality of life assessment in advanced non-small-cell lung cancer patients undergoing an accelerated radiotherapy regimen: report of ECOG study 4593. Eastern Cooperative Oncology Group.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1199-206
AD - University of Wisconsin Medical School, Madison, WI 53792, USA.
PURPOSE: To prospectively evaluate the quality of life (QOL) before, at completion, and after therapy for patients receiving an accelerated fractionation schedule of radiotherapy for advanced, unresectable non-small-cell lung cancer in a Phase II multi-institutional trial. METHODS AND MATERIALS: The Functional Assessment of Cancer Therapy-Lung (FACT-L) patient questionnaire was used to score the QOL in patients enrolled in the Eastern Cooperative Oncology Group Phase II trial (ECOG 4593) of hyperfractionated accelerated radiotherapy in non-small-cell lung cancer. Radiotherapy (total dose 57.6 Gy in 36 fractions) was delivered during 15 days, with three radiation fractions given each treatment day. The protocol was activated in 1993, and 30 patients had accrued by November 1995. The FACT-L questionnaire was administered at study entry (baseline), on the last day of radiotherapy (assessment 2), and 4 weeks after therapy (assessment 3). The FACT-L includes scores for physical, functional, emotional, and social well-being (33 items), and a subscale of lung cancer symptoms (10 additional items). The summation of the physical, functional, and lung cancer symptom subscales (21 items) constitutes the Trial Outcome Index (TOI), considered the most clinically relevant outcome measure in lung cancer treatment trials. RESULTS: The FACT-L completion rates at the designated study time points were as follows: baseline, 30 of 30 (100%); assessment 2, 29 (97%) of 30; and assessment 3, 24 (80%) of 30. At treatment completion, statistically significant declines in QOL scores were noted, compared with baseline for physical and functional well-being. Emotional well-being scores improved at both assessment 2 and assessment 3. The physical and functional scores returned approximately to baseline values at assessment 3. The change in TOI score was evaluated as a function of the clinical response to treatment, toxicity grade, and survival; no clear association was noted. A trend for the largest decrease in QOL was noted for patient groups with shorter survival times. The mean change in the TOI score from baseline to assessment 3 was -8.96 for patients surviving < 52 weeks vs. -0.95 for those surviving > 52 weeks. CONCLUSIONS: The FACT-L questionnaire can be successfully administered to non-small-cell lung cancer patients enrolled in a prospective Phase II trial of accelerated radiation fractionation. The decrement in physical and functional QOL during treatment returned to baseline level at 4 weeks after treatment. Emotional well-being improved at all time points. A trend was noted for shorter survival times in patients with the largest negative change in TOI score. These data suggest that the clinical use of hyperfractionated accelerated radiotherapy did not cause a significant, long-term decrease in the QOL of the treated patients, and that it is feasible to perform a QOL study of patients enrolled in such a trial.

2
UI - 21406685
AU - Jatoi A; Daly BD; Hughes VA; Dallal GE; Kehayias J; Roubenoff R
TI - Do patients with nonmetastatic non-small cell lung cancer demonstrate altered resting energy expenditure?
SO - Ann Thorac Surg 2001 Aug;72(2):348-51
AD - Department of Medicine, The New England Medical Center, Tufts University, Boston, Massachusetts, USA. jatoi.aminah@mayo.edu
BACKGROUND: The cancer cachexia syndrome occurs in patients with non-small cell lung cancer (NSCLC) and includes elevated resting energy expenditure (REE). This increase in REE leads to weight loss, which in turn confers a poor prognosis. This study was undertaken to determine whether the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC. METHODS: In this case-control study, 18 patients with nonmetastatic NSCLC (stages IA to IIIB) were matched to healthy controls on age (+/- 5 years), gender, and body mass index (+/- 3 kg/m2). Only 4 cancer patients had experienced > 5% weight loss. Cancer patients and controls were compared on the basis of: (1) unadjusted REE, as measured by indirect calorimetry; (2) REE adjusted for lean body mass, as measured by dual x-ray absorptiometry; (3) REE adjusted for body cell mass, as measured by potassium-40 measurement; and (4) REE adjusted for total body water, as measured by tritiated water dilution. RESULTS: We observed no significant difference in unadjusted REE or in REE adjusted for total body water. However, with separate adjustments for lean body mass and body cell mass, cancer patients manifested an increase in REE: mean difference +/- standard error of the mean: 140+/-35 kcal/day (p = 0.001) and 173+/-65 kcal/day (p = 0.032), respectively. Further adjustment for weight loss yielded similarly significant results. CONCLUSIONS: These results suggest that the cancer cachexia syndrome occurs in patients with nonmetastatic NSCLC and raise the question of whether clinical trials that target cancer cachexia should be initiated before weight loss.

3
UI - 21406686
AU - Suzuki K; Nagai K; Yoshida J; Nishimura M; Nishiwaki Y
TI - Predictors of lymph node and intrapulmonary metastasis in clinical stage IA non-small cell lung carcinoma.
SO - Ann Thorac Surg 2001 Aug;72(2):352-6
AD - Division of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. kjsuzuki@ncc.go.jp
BACKGROUND: The feasibility of limited surgical resection for clinical stage IA non-small cell lung cancer still remains controversial. METHODS: From July 1987 through April 1998, 389 patients with clinical stage IA disease underwent major lung resection and complete mediastinal lymph node dissection. Univariate and multivariable analyses were performed to determine predictors of local or regional tumor spread: pathologic lymph node involvement, intrapulmonary metastases, and lymphatic invasion. RESULTS: Of the 389 patients, 88 (23%) had lymph node involvement or intrapulmonary metastases pathologically. According to multivariable analyses, grade of differentiation and pleural involvement were significant predictors of local or regional tumor spread (p < 0.01). Based on these results, more than 40% of clinical stage IA non-small cell lung cancer patients showed pathologic lymph node involvement or intrapulmonary metastases, or both, if the patients had both of the predictors of pathologic local or regional involvement: moderate or poor differentiation of the primary tumor and pleural involvement by tumor cells. CONCLUSIONS: Limited surgical resection is not feasible for clinical stage IA non-small cell lung cancer, especially when the tumor shows moderate or poor differentiation, or pleural involvement.

4
UI - 21406687
AU - Hollaus PH; Janakiev D; Pridun NS
TI - Telescope anastomosis in bronchial sleeve resections with high-caliber mismatch.
SO - Ann Thorac Surg 2001 Aug;72(2):357-61
AD - Department of Thoracic Surgery, Otto Wagner Hospital, Vienna, Austria. peter.hollaus@pul.magwein.gv.at
BACKGROUND: The efficacy of bronchial telescope anastomosis was evaluated retrospectively in patients undergoing sleeve resections with high-caliber mismatch. METHODS: The hospital charts of patients undergoing upper and lower sleeve bilobectomy and lower lobe lobectomy with replantation of the middle lobe or upper lobe into the mainstem bronchus were retrospectively reviewed. Age, sex, side, TNM stage, preoperative forced expiratory volume in 1 second (FEV1 [%]), preoperative risk factors, postoperative course, survival (months), and causes of death were recorded. RESULTS: Fifteen patients suffering from bronchial carcinoma were operated on. In 6 cases FEV1 was less than 2 L (FEV1 49% to 80%, mean 64.3, median 61). Three patients were 70 years and older. There were 7 high-risk cases presenting with coronary heart disease (n = 3), chronic alcoholism (n = 3), cerebrovascular disease (n = 1), and active tuberculosis (n = 1). Local radicality was achieved in all patients but 1, in whom pneumonectomy was contraindicated. There was no postoperative mortality. Early complications consisted of 1 anastomotic dehiscence successfully closed with an intercostal flap and 1 patient with bilateral pneumonia requiring mechanical ventilation for 5 days. One parenchymal fistula led to prolonged drainage; in 1 patient pneumothorax after removal of the chest tube required redrainage. There were no late complications, and no anastomotic stenosis developed. Survival ranged from 12 to 56 months (median 29.8, mean 30, SD 15.7). Seven patients died between 3.9 and 14 months postoperatively (mean 8.5, median 6.9) of intrabronchial local recurrence (n = 1), distant recurrence (n = 3), intrathoracic recurrence (n = 1), and nontumor-related causes (n = 2). CONCLUSIONS: Telescope anastomosis is a safe and efficient technique of bronchial sleeve resection.

5
UI - 21413068
AU - Touboul E; Lagrange JL; Theobald S; Astoul P; Baldeyrou P; Bardet E; Bazelly B; Brechot J; Breton JL; Douillard JY; Grivaux M; Jacoulet P; Khalil A; Le Chevalier T; Lemarie E; Martinet Y; Massard G; Milleron B; Moro-Sibilot D; Paesmans M; Pujol JL; Quoix AE; Ranfaing E; Riviere A; Sancho-Garnier H; Souquet PJ; Spaeth D; Stoebner-Delbarre A; Thiberville L; Vaylet F; Vergnon JM; Westeel V; Depierre A
TI - [Standards, Options and Recommendations for the management of stage I or II primary bronchial cancers treated exclusively with radiotherapy]
SO - Cancer Radiother 2001 Aug;5(4):452-63
AD - Hopital Tenon, Paris, France.
CONTEXT: The 'Standards, Options and Recommendations' (SOR) project, started in 1993, is a collaboration between the Federation of the French Cancer Centres (FNCLCC), the 20 French cancer centres and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and outcome for cancer patients. The methodology is based on literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone. METHODS: Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French cancer centres. RESULTS: The main recommendations for the management of stage I and II non small cell lung carcinoma treated by radiotherapy alone are: 1) The curative external irradiation with a continual course is an alternative to surgery only in the case of medically inoperable tumors or because the patient refuses surgery; 2) The external irradiation of the primary tumor only without the mediastinum could be proposed in peripheral stage IA. In proximal stage IA and IB, external irradiation should be carried out only as part of prospective randomised controlled trials comparing a localised irradiation of the primary tumor with a large irradiation of the mediastinum and the primary tumor. The treated volume must include the macroscopic tumoral volume with or without the microscopic tumoral volume and with a security margin from 1.5 to 2 cm; 3) There is a benefit to delivering a total dose in the primary tumor higher than 60 Gy in so far as the proposed irradiation, taking into account the respiratory function, does not increase the likelihood of severe adverse events due to radiation; and 4) The change in fractionation, the radiochemotherapy combination, the endobronchial brachytherapy with high dose rate alone or with external irradiation could be proposed only as part of prospective controlled trials for tumors classified as stage IB or II.

6
UI - 21416723
AU - Shirakusa T
TI - [Less invasive treatment for lung carcinoma]
SO - Gan To Kagaku Ryoho 2001 Aug;28(8):1057-62
AD - Second Dept. of Surgery, School of Medicine, Fukuoka University, 45-1 Nanakuma, Fukuoka 814-0180, Japan.
Today, less invasive treatments for lung carcinoma are divided to two categories. One is the surgical option which includes 1. surgery by muscle sparing thoracotomy, 2. reduced operation represented by segmentectomy or partial resection, 3. so-called VATS (video-assisted thoracoscopic surgery), and 4. sentinel node navigation surgery. Other options such as photodynamic therapy or brachytherapy are also very useful for the treatment of superficial malignancies at the hilar zone, because of their lower level of invasiveness.

7
UI - 21232735
AU - Arnau Obrer A; Martin Diaz E; Perez Alonso D; Regueiro Mira F; Cervera Juan A; Granell Gil M; Roch Penderia S; Canto Armengod A
TI - [Surgical treatment of non-small cell lung cancer with mediastinal node invasion. A retrospective study]
SO - Arch Bronconeumol 2001 Mar;37(3):121-6
AD - Servicios de Cirugia Toracica. Hospital General Universitario de Valencia, Spain.
OBJECTIVE: To analyze the survival of patients classified as N2M0 (N2 by cytohistology) with non-small cell lung cancer treated by surgical resection of the primary tumor and lymphadenectomy. PATIENTS AND METHODS: Among 1043 consecutive patients with lung cancer who were considered for surgery between 1990 and 2000, 155 were classified N2M0 by histology. Surgical exeresis of the primarily pulmonary tumor and lymphadenectomy were performed in 116 patients of the 130 patients who underwent thoracotomy. Among the 116 N2M0 patients undergoing surgical resection, 23 were diagnosed N2c(C3) by mediastinoscopy and/or mediastinotomy and were given induction chemotherapy (ChT) (mitomycin/ifosfami-de/cisplatin, 3 cycles) and 93 were diagnosed N2pM0 based on samples obtained from mediastinal lymph tissue during thoracotomy. Nineteen of the latter had previously been classified negative during surgical exploration. The patients diagnosed N2p after thoracotomy were given adjuvant ChT, radiotherapy or both. N2p patients who received induction therapy were given radiotherapy. Those found negative after lymphadenectomy and patients with severe disease were given no adjuvant treatment. RESULTS: Mean survival was 18 months for resected patients diagnosed N2 by mediastinoscopy/mediastinotomy and with induction ChT and survival at one, two and five years was 80%, 45% and 30%, respectively. No postoperative mortality was recorded in this group. One patient suffered bronchopleural fistula. Nine patients showed no residual mediastinal node disease after lymphadenectomy. The mean survival of resected patients diagnosed N2p by thoracotomy was 13 months, and one, two and five year survival rates were 56%, 31% and 19%, respectively. Fourteen patients died within 30 days of surgery. Nine patients developed a bronchopleural fistula. The difference in survival of the two groups was not significant. CONCLUSIONS: The prognosis after cytohistologic confirmation of N2 disease can be considered poor. Standard, complete surgery plus induction therapy in screened patients improved survival for those diagnosed N2 by thoracotomy, with no statistically significant differences.

8
UI - 21236679
AU - Korst RJ; Ginsberg RJ
TI - Appropriate surgical treatment of resectable non-small-cell lung cancer.
SO - World J Surg 2001 Feb;25(2):184-8
AD - Thoracic Service, Department of Surgery, Room C868, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. korstr@mskcc.org
Patients with early-stage non-small-cell lung cancer (NSCLC) should be treated with complete surgical resection whenever possible. Incomplete resections do not cure, and the optimal pulmonary resection is anatomic lobectomy. Limited resections (wedge resection and segmentectomy) are associated with a threefold increase in local recurrence, which translates into decreased survival. The addition of mediastinal lymph node dissection produces the best pathologic staging but has never been shown to improve survival. Resections can be performed through a variety of incisions and even using minimally invasive techniques, but posterolateral thoracotomy seems to provide the best exposure and is used most frequently. Adjuvant radiotherapy in both the preoperative and postoperative settings does not improve survival in patients with resected NSCLC. Similarly, postoperative chemotherapy cannot be advocated in these patients based on the current data. Improved survival has been demonstrated in the randomized setting for patients with locally advanced, resectable disease (N2) using preoperative (induction) chemo(radio)therapy, but the numbers are small. Patients with this stage of NSCLC should be enrolled in induction therapy protocols whenever possible to confirm the efficacy of this approach.

9
UI - 21251183
AU - Di Giorgio A; Sammartino P; Canavese A; Arnone P; Sibio S; Accarpio F; Al Mansour M
TI - [Immunomorphology of lymph nodes and prognosis in lung cancer]
SO - Minerva Chir 2001 Apr;56(2):153-9
AD - Dipartimento di Chirurgia Pietro Valdoni, Universita degli Studi La Sapienza, Rome, Italy.
BACKGROUND: Many studies have investigated locoregional immune responses and long-term survival in various types of cancer; few have focused on lung cancer. This study was designed to assess the prognostic value of immunomorphologic changes in locoregional lymph nodes in patients resected for bronchogenic carcinoma. METHODS: In a retrospective analysis, immune responses in locoregional lymph nodes were studied histologically in 172 selected patients. Lymph node morphology was studied according to the system of Cottier et al.: sinus histiocytosis (SH) and paracortical lymphoid cell hyperplasia (PCA) were considered as a cellular immune response, and follicular hyperplasia of the cortical area (CA) as a humoral reaction. The survival rate was estimated by the Kaplan-Meier product-limit method. Log-rank test and Cox proportional-hazards model were used to determine statistical significance in univariate and multivariate survival analysis. RESULTS: 35.5% of the patients had no evident response in regional nodes; 19.8% had a marked cellular response; 11% a marked humoral response; and 33.7% a mixed cellular-humoral response. A nodal cellular response improved long-term survival rates even in patients with regional node metastases. Multivariate analysis identified an independent variable as having high prognostic value: lymph node immunoreactivity. CONCLUSIONS: Lymph node immunoreactivity significantly influences long-term survival after curative surgery for lung cancer and may be useful in stratifying patients for prospective trials of adjuvant treatment including immunotherapy.

10
UI - 21397307
AU - Iizasa T; Fujisawa T
TI - [Surgery for non-small cell lung cancer based on the T factor]
SO - Nippon Geka Gakkai Zasshi 2001 Jul;102(7):507-10
AD - Department of Thoracic Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
We review the indications of surgery in patients with non-small cell lung cancer (NSCLC) based on the T factor, focusing on peripheral small tumors, invasion to other organs, and the presence of malignant pleural effusion or intrapulmonary metastasis. While limited surgery in patients with peripheral, small-sized NSCLC preserves postoperative pulmonary function, the prospects for long-term survival are reduced due to the likelihood of recurrence, Novel prospective studies are being conducted to determine the indications for limited surgery in such patients which focus on histology, tumor size, and pulmonary function. In some patients with locally advanced disease, especially with invasion of the chest wall (T3), pericardium (T3), left atrium (T4), great vessel (T4), and carina (T4) and with malignant pleural effusion found intraoperatively and ipsilateral intrapulmonary metastasis, complete resection results in long-term survival. Thus surgery should be considered in patients without N2 disease.

11
UI - 21397308
AU - Saito M; Miura T; Furukawa K; Kato H
TI - [Reevaluation of the surgical indications for lung cancer based on the N factor]
SO - Nippon Geka Gakkai Zasshi 2001 Jul;102(7):511-6
AD - Department of Chest Surgery, Tokyo Medical University, Kasumigaura Hospital, Ibaraki, Japan.
The Standard surgical treatment for stage I, II, and IIIa non-small cell lung cancer (NSCLC) is lobectomy with systemic mediastinal lymph node dissection. More than 50% of our series of 220 patients with cN2 disease were classified as pN0-1. The postoperative 5-year survival rate of patients with cN2 disease was 36%, and that of those with cN2-pN2 disease was 18%. Tumor cell type, surgical technique, or site of tumor had no prognostic significance, although pN, cT, and number of N2 sites were of prognostic significance. We conclude that the indications for surgery are T1-2 N2 disease with a single N2 site.

12
UI - 21397310
AU - Yoshimura M; Tsubota N
TI - [Wedge resection for lung cancer]
SO - Nippon Geka Gakkai Zasshi 2001 Jul;102(7):521-4
AD - Department of Thoracic Surgery, Kobe University School of Medicine, Kobe, Japan.
The role of wedge resection in lung cancer is reviewed. In the past century, many reports appeared dealing with limited resection for lung cancer, and it is clear that wedge resection should be performed in patients who are considered at high risk for not tolerating lobectomy; still there is no prospective or even retrospective study on wedge resection carried out in candidates for lobectomy. In recent years, progress in imaging diagnostic technology using high-resolution computed tomography has increased the opportunity to diagnose early adenocarcinoma presenting as small ground-glass opacity (GGO) which could not be detected on chest radiographs. Some patients with GGO may become candidates for wedge resection in this century, if additional favorable data result from prospective studies relevant to imaging diagnosis, pathology, and prognosis.

13
UI - 21397311
AU - Shirakusa T
TI - [Video-assisted thoracoscopic surgery lobectomy for lung carcinoma]
SO - Nippon Geka Gakkai Zasshi 2001 Jul;102(7):525-9
AD - Second Department of Surgery, Fukuoka University, School of Medicine, Fukuoka, Japan.
Video-assisted thoracoscopic surgery (VATS) has been utilized worldwide for the treatment of various types of thoracic disease, in particular for lung carcinoma. The following criteria are accepted as the operative indications for VATS lobectomy: i) clinical T1N1M0: ii) tumor located in the peripheral zone; and iii) non-small cell carcinoma. Videoscopic surgery has the merit of being less invasive, resulting in a low level of postoperative chest pain, short incisional scar, and short duration of hospital stay. Right-side upper mediastinal lymph node dissection is easy under the thoracoscope, although compared with standard thoracotomy it is not always possible to perform complete level II dissection on the left, because of the difficult approach to lymph nodess No. 3 and No. 4 under the aortic arch via the thoracoscope. The postoperative 5-year survival rate after VATS lobectomy is superior to that after standard thoracotomy. It is expected that the indications for VATS will be expanded to include T2 or N1 disease as thorascopic instruments and techniques improve.

14
UI - 21397314
AU - Ichinose Y
TI - [Reevaluation of the surgical indications for non-small cell lung cancer based on the results of postoperative treatment]
SO - Nippon Geka Gakkai Zasshi 2001 Jul;102(7):541-5
AD - Department of Chest Surgery, National Kyushu Cancer Center, Fukuoka, Japan.
Patients who undergo complete surgical resection for pathological stage I-IIIa non-small cell lung cancer (NSCLC) are candidates for postoperative chemo- and/or radiotherapy. The indications for surgical resection are not a problematic issue, regardless of the results of postoperative therapy. So far there have been no definitively positive results in randomized phase III trials comparing postoperative adjuvant therapy with no further therapy. Therefore clinical trials should be conducted to determine the most appropriate postoperative regimen in NSCLC.

15
UI - 21432359
AU - Macbeth F; Saunders M
TI - Synchronous chemoradiation for squamous carcinomas. This treatment is not gold standard for lung cancer.
SO - BMJ 2001 Aug 25;323(7310):453

16
UI - 21433650
AU - Mac Manus MP; Hicks RJ; Ball DL; Kalff V; Matthews JP; Salminen E; Khaw P; Wirth A; Rischin D; McKenzie A
TI - F-18 fluorodeoxyglucose positron emission tomography staging in radical radiotherapy candidates with nonsmall cell lung carcinoma: powerful correlation with survival and high impact on treatment.
SO - Cancer 2001 Aug 15;92(4):886-95
AD - Department of Radiation Oncology, Peter MacCallum Cancer Institute, A'Beckett Street, Melbourne, Victoria 3000, Australia. mmanus@petermac.unimelb.edu.au
BACKGROUND: Successful treatment of nonsmall cell lung carcinoma (NSCLC) with radical radiotherapy (RT) requires accurate delineation of tumor extent. Conventional computed tomography-based noninvasive staging often estimates intrathoracic thoracic tumor extent incorrectly and fails to detect distant metastasis. High sensitivity and specificity are reported for F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) staging in potentially resectable NSCLC. The authors investigated FDG-PET staging in radical RT candidates with unresectable NSCLC. METHODS: The authors prospectively studied 153 consecutive patients with unresectable NSCLC who were candidates for radical RT after conventional staging and had PET scans. Patients were allocated both "before PET" and "after PET" stages. Subsequent management was recorded. Survival analysis was used to compare validity of pre-PET and post-PET staging. RESULTS: After PET, 107 patients (70%) actually received radical therapies (radical RT with or without concurrent chemotherapy, n = 102; radical surgery, n = 5); 46 patients (30%) received palliative treatment because of PET-detected distant metastasis (n = 28; 18%) or extensive locoregional disease (n = 18; 12%). Palliative therapies were RT (n = 33), chemotherapy (n = 12), or supportive care (n = 1). All five surgically treated patients underwent potentially curative resections after downstaging by PET. For radically treated patients, post-PET stage (P = 0.0041) but not pre-PET stage (P = 0.19) was strongly associated with survival. Radically treated patients survived longer than those treated palliatively (P = 0.02; 1-year survival, 69% and 44%, respectively; 2-year survival, 44% radical; no palliative patients had 2-yr follow-up). CONCLUSIONS: Positron emission tomography-assisted staging detected unsuspected metastasis in 20%, strongly influenced choice of treatment strategy, frequently impacted RT planning, and was a powerful predictor of survival. Potential impact of FDG-PET is even greater in radical RT candidates with NSCLC than in surgical candidates. Copyright 2001 American Cancer Society.

17
UI - 21424065
AU - Anscher MS; Marks LB; Shafman TD; Clough R; Huang H; Tisch A; Munley M; Herndon JE 2nd; Garst J; Crawford J; Jirtle RL
TI - Using plasma transforming growth factor beta-1 during radiotherapy to select patients for dose escalation.
SO - J Clin Oncol 2001 Sep 1;19(17):3758-65
AD - Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA. anscher@radonc.duke.edu
PURPOSE: The ability to prescribe treatment based on relative risks for normal tissue injury has important implications for oncologists. In non-small-cell lung cancer, increasing the dose of radiation may improve local control and survival. Changes in plasma transforming growth factor beta (TGFbeta) levels during radiotherapy (RT) may identify patients at low risk for complications in whom higher doses of radiation could be safely delivered. PATIENT AND METHODS: Patients with locally advanced or medically inoperable non-small-cell lung cancer received three-dimensional conformal RT to the primary tumor and radiographically involved nodes to a dose of 73.6 Gy (1.6 Gy twice daily). If the plasma TGFbeta level was normal after 73.6 Gy, additional twice daily RT was delivered to successively higher total doses. The maximum-tolerated dose was defined as the highest radiation dose at which < or = one grade 4 (life-threatening) late toxicity and < or = two grade 3 to 4 (severe life-threatening) late toxicities occurred. RESULTS: Thirty-eight patients were enrolled. Median follow-up was 16 months. Twenty-four patients were not eligible for radiation dose escalation beyond 73.6 Gy because of persistently abnormal TGFbeta levels. Fourteen patients whose TGFbeta levels were normal after 73.6 Gy were escalated to 80 Gy (n = 8) and 86.4 Gy (n = 6). In the 86.4-Gy group, dose-limiting toxicity was reached because there were two (33%) grade 3 late toxicities. CONCLUSION: It is feasible to use plasma TGFbeta levels to select patients for RT dose escalation for non-small-cell lung cancer. The maximum-tolerated dose using this approach is 86.4 Gy.

18
UI - 21268240
AU - Timothy AR; Girling DJ; Saunders MI; Macbeth F; Hoskin PJ; Second Workshop on Palliative Radiotherapy and Symptom Control
TI - Radiotherapy for inoperable lung cancer.
SO - Clin Oncol (R Coll Radiol) 2001;13(2):86-7
AD - St Thomas' Hospital, London, UK.

19
UI - 21268243
AU - Quddus AM; Kerr GR; Price A; Gregor A
TI - Long-term survival in patients with non-small cell lung cancer treated with palliative radiotherapy.
SO - Clin Oncol (R Coll Radiol) 2001;13(2):95-8
AD - Western General Hospital, Edinburgh, UK.
The aim of palliative thoracic radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) is to alleviate symptoms. This study was designed to determine whether any patients achieved long-term survival after this treatment. In Edinburgh, between 1974 and 1993, 4531 patients were treated with palliative radiotherapy for NSCLC, receiving ten fractions or fewer. We reviewed the case notes of the long-term survivors. Sixty-one (1.3%; 95% confidence interval (CI) 1.0-1.6) patients survived for more than 5 years; 43 (70%) had histological confirmation of cancer; 28 (46%) had stage Stage I or II, 28 (46%) Stage III and one Stage IV disease; 53 (87%) patients were treated with doses of 30-35 Gy in ten daily fractions, seven (12%) received 20 Gy in five daily fractions and one received a 10 Gy single fraction. Forty-two (69%) patients had a radiological complete response, 16 (26%) a partial response and the remainder stable disease. Clinically significant radiation pneumonitis occurred in one (2%) patient, radiation myelopathy in two (3%) and multiple rib fractures in one (2%). There did not appear to be an association between long-term survival and a radiosensitive phenotype. On univariate analysis, long-term survival was more frequent in patients receiving ten-fraction regimens than in those who underwent a shorter course of radiotherapy (chi 2 = 19.5, P < 0.001). Thirty-four (0.8%; 95% CI 0.6-1.0) patients were disease free at death or at last review (median 10 years; range 5-17). We conclude that palliative thoracic radiotherapy produces long-term survival in 1.3% and personal cure in up to 1% of patients with advanced NSCLC.

20
UI - 21407948
AU - Werner-Wasik M; Xiao Y; Pequignot E; Curran WJ; Hauck W
TI - Assessment of lung cancer response after nonoperative therapy: tumor diameter, bidimensional product, and volume. A serial CT scan-based study.
SO - Int J Radiat Oncol Biol Phys 2001 Sep 1;51(1):56-61
AD - Kimmel Cancer Center of Jefferson Medical College, Philadelphia, PA 19107, USA. maria.werner-wasik@mail.tju.edu
PURPOSE: Tumor response after nonoperative lung cancer therapy is traditionally evaluated by bidimensional measurement of maximum tumor diameters. The purpose of this analysis is to investigate whether tumor largest dimension (based on RECIST [Response Evaluation Criteria In Solid Tumors]), bidimensional tumor product, and volume correlate with each other in evaluating tumors of patients with locally advanced non-small-cell lung cancer (NSCLC). In addition, the pace of locally advanced NSCLC volumetric response over time, as well as the prognostic value of tumor size, was assessed in this report with software-assisted evaluation of sequential tumor measurement. METHODS AND MATERIALS: Patients with locally advanced NSCLC treated with thoracic radiotherapy (RT) with or without chemotherapy were included, if the following were available: a pretreatment computed tomography (CT) simulation and at least two follow-up diagnostic thoracic CT scans taken at our institution after 1996 that were available in Dicom format for electronic transfer of images from diagnostic radiology to a computer terminal with commercial statistics software (AcQsim/CMS Focus). Primary lung tumor and grossly involved lymph nodes were contoured manually on pre-RT axial images and on all follow-up CT scans. Tumor/lymph node largest dimensions, bidimensional products (BP), and volumes were measured using the same software. Data were presented as percent change in volume or unidimensional and bidimensional measurements, with the CT simulation measurements serving as baseline. RESULTS: A total of 22 patients were evaluated. The median thoracic RT dose was 62.4 Gy (range: 50.0-69.6), and all patients had a Karnofsky performance status > or =80. Chemotherapy (mostly carboplatin/paclitaxel) was given to 17 patients. Nineteen patients had Stage III NSCLC; 1 patient was in Stage I, 1 was in Stage IV, and 1 was recurrent. A total of 107 thoracic CT scans (22 pretreatment and 85 follow-up), averaging 4.9 scans per patient, were analyzed. Tumors reached the smallest volume at a median of 11.0 months from RT completion in all patients, 8.5 months in patients who subsequently failed locally (n = 8), and 11.9 months in those who did not fail locally. Failure rates were as follows: in-field, 36% (8/22); intrathoracic (lung nodules, effusion, pleura), 55% (12/22); and distant, 50% (11/22). Eleven patients are still alive, 4 free of disease. Overall median survival time (MST) is 27.3 months. The median initial tumor volume was 88.0 cc (range: 3.8-218) for all patients; median BP was 33.0 cm(2) (range: 3.1-112.1), and median tumor largest dimension was 7.6 cm (range: 2.2-13.5). The MST of patients with initial tumor volume < or =63.0 cc (n = 9) was >53.0 months and of those with tumor volume > 63.0 cc was 17.3 months. The MST of patients (n = 6) with initial bidimensional tumor product < or =16 cm(2) was >53.0 months and of those with tumor product >16 cm(2) was 17.3 months. The MST of patients with largest initial dimension < or =4 cm was >53.1 months and of those with largest dimension > 4 cm was 25.0 months. At 24 months, 79% of patients with a tumor volume < or =124.0 cc (n = 18) had locally controlled tumors, vs. 0% of patients with tumor volumes >124.0 cc. At the same time point, 93% of patients with BP < or =40 cm(2) were locally controlled, vs. 0% of those with BP > 40 cm(2); 100% of patients with tumor dimensions < or =7.5 cm were locally controlled, vs. 40% of those with dimensions >7.5 cm. The partial responses in our series (assessed as the best response obtained during observation period) were as follows: 4 patients assessed based on either dimension only, product only, or volume only; 15 partial responses based on dimension or product; 16 partial responses based on volume alone; 3 cases of no tumor response, based on dimension or product; and 2 cases based on tumor volume alone. That represents good to excellent agreement among all three methods of measurement. CONCLUSIONS: (1) The response of locally advanced NSCLC to nonoperative therapy is a slow process, with tumor volumes reaching their nadir several months after treatment. (2) Smaller initial tumor size, as measured by largest tumor dimension, bidimensional product, or tumor volume, is associated with better local control and survival than larger initial measurements. (3) Any of the three tumor measurements (largest dimension, bidimensional product, or volume) can be used as a reliable tool in assessing lung cancer response to nonoperative therapy. This confirms further the validity of RECIST and does not suggest that tumor volume is significantly superior for response evaluation.