Publications by authors named "Andrew T Turrisi"

31 Publications

Treatment of Small-Cell Lung Cancer: American Society of Clinical Oncology Endorsement of the American College of Chest Physicians Guideline.

J Clin Oncol 2015 Dec 8;33(34):4106-11. Epub 2015 Sep 8.

Charles M. Rudin and M. Catherine Pietanza, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; Nofisat Ismaila, American Society of Clinical Oncology, Alexandria, VA; Christine L. Hann, Johns Hopkins University, Baltimore, MD; Narinder Malhotra, Correct Care Solutions, Pittsburgh; Andrew T. Turrisi III, DeltaMedix, Scranton, PA; Benjamin Movsas, Henry Ford Hospital, Detroit, MI; Kim Norris, Lung Cancer Foundation of America, Los Angeles, CA; Suresh S. Ramalingam, Emory University, Atlanta, GA; and Giuseppe Giaccone, Georgetown University, Washington, DC.

Purpose: The American College of Chest Physicians (ACCP) produced an evidence-based guideline on treatment of patients with small-cell lung cancer (SCLC). Because of the relevance of this guideline to American Society of Clinical Oncology (ASCO) membership, ASCO reviewed the guideline, applying a set of procedures and policies used to critically examine guidelines developed by other organizations.

Methods: The ACCP guideline on the treatment of SCLC was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel updated the literature search, reviewed the content, and considered additional recommendations.

Results: The ASCO Endorsement Panel determined that the recommendations from the ACCP guideline, published in 2013, are clear, thorough, and based on current scientific evidence. ASCO endorses the ACCP guideline on the treatment of SCLC, with the addition of qualifying statements.

Recommendations: Surgery is indicated for selected stage I SCLC. Limited-stage disease should be treated with concurrent chemoradiotherapy in patients with good performance status. Thoracic radiotherapy should be administered early in the course of treatment, preferably beginning with cycle one or two of chemotherapy. Chemotherapy should consist of four cycles of a platinum agent and etoposide. Extensive-stage disease should be treated primarily with chemotherapy consisting of a platinum agent plus etoposide or irinotecan. Prophylactic cranial irradiation prolongs survival in patients with limited-stage disease who achieve a complete or partial response to initial therapy and may do so in similarly responding patients with extensive-stage disease as well. Additional information is available at http://www.asco.org/endorsements/sclc and http://www.asco.org/guidelineswiki.
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http://dx.doi.org/10.1200/JCO.2015.63.7918DOI Listing
December 2015

Hyperfractionated or accelerated radiotherapy in lung cancer: an individual patient data meta-analysis.

J Clin Oncol 2012 Aug 2;30(22):2788-97. Epub 2012 Jul 2.

Institut de Cance´rologie Gustave-Roussy, Villejuif, France.

Purpose: In lung cancer, randomized trials assessing hyperfractionated or accelerated radiotherapy seem to yield conflicting results regarding the effects on overall (OS) or progression-free survival (PFS). The Meta-Analysis of Radiotherapy in Lung Cancer Collaborative Group decided to address the role of modified radiotherapy fractionation.

Material And Methods: We performed an individual patient data meta-analysis in patients with nonmetastatic lung cancer, which included trials comparing modified radiotherapy with conventional radiotherapy.

Results: In non-small-cell lung cancer (NSCLC; 10 trials, 2,000 patients), modified fractionation improved OS as compared with conventional schedules (hazard ratio [HR] = 0.88, 95% CI, 0.80 to 0.97; P = .009), resulting in an absolute benefit of 2.5% (8.3% to 10.8%) at 5 years. No evidence of heterogeneity between trials was found. There was no evidence of a benefit on PFS (HR = 0.94; 95% CI, 0.86 to 1.03; P = .19). Modified radiotherapy reduced deaths resulting from lung cancer (HR = 0.89; 95% CI, 0.81 to 0.98; P = .02), and there was a nonsignificant reduction of non-lung cancer deaths (HR = 0.87; 95% CI, 0.66 to 1.15; P = .33). In small-cell lung cancer (SCLC; two trials, 685 patients), similar results were found: OS, HR = 0.87, 95% CI, 0.74 to 1.02, P = .08; PFS, HR = 0.88, 95% CI, 0.75 to 1.03, P = .11. In both NSCLC and SCLC, the use of modified radiotherapy increased the risk of acute esophageal toxicity (odds ratio [OR] = 2.44 in NSCLC and OR = 2.41 in SCLC; P < .001) but did not have an impact on the risk of other acute toxicities.

Conclusion: Patients with nonmetastatic NSCLC derived a significant OS benefit from accelerated or hyperfractionated radiotherapy; a similar but nonsignificant trend was observed for SCLC. As expected, there was increased acute esophageal toxicity.
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http://dx.doi.org/10.1200/JCO.2012.41.6677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934452PMC
August 2012

Recall those thrilling days of yesteryear ...

Authors:
Andrew T Turrisi

Oncologist 2010 2;15(11):1133-4. Epub 2010 Nov 2.

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http://dx.doi.org/10.1634/theoncologist.2010-0311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3227906PMC
June 2011

Once-daily radiotherapy to > or =59.4 Gy versus twice-daily radiotherapy to > or =45.0 Gy with concurrent chemotherapy for limited-stage small-cell lung cancer: a comparative analysis of toxicities and outcomes.

Jpn J Radiol 2010 Jun 30;28(5):340-8. Epub 2010 Jun 30.

Department of Radiation Oncology, Medical University of South Carolina, Charleston, SC 29425, USA.

Purpose: The aim of this study was to compare toxicities, disease control, survival outcomes, and patterns of failure between groups of limited-stage small-cell lung cancer patients treated with once-daily versus twice-daily radiotherapy and concurrent chemotherapy.

Materials And Methods: This single-institution retrospective analysis included a comparison of two of radiotherapy regimens to planned doses of (1) > or =59.4 Gy at 1.8-2.0 Gy per once-daily fraction or (2) > or =45 Gy at 1.5 Gy per twice-daily fractions with concurrent platinum-based chemotherapy. Comparative analyses of toxicities and disease control were performed.

Results: A total of 71 patients were included in the present study (17 once-daily, 54 twice-daily). Patient, tumor, staging, and treatment factors were similar between the two treatment groups. Median planned radiotherapy doses were 60 Gy (range 59.4-70.0 Gy) and 45 Gy (range 45-51 Gy) for the once-daily and twice-daily groups, respectively. Acute toxicities were similar between the groups ( approximately 20% grade 3 esophagitis). At a median survival follow-up of 26.2 months (range 3.4-85.5 months), 42 patients had died. The 2-year overall survival estimates were similar at 43% and 49% for the once-daily versus twice-daily groups, respectively. Isolated in-field failures were similar between the two groups ( approximately 17%).

Conclusion: The present analysis did not detect a statistically significant difference in acute toxicities, disease control, or survival outcomes in limited-stage small-cell lung cancer patients treated with concurrent chemotherapy and once-daily versus twice-daily radiotherapy.
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http://dx.doi.org/10.1007/s11604-010-0429-xDOI Listing
June 2010

Phase I study of accelerated conformal radiotherapy for stage I non-small-cell lung cancer in patients with pulmonary dysfunction: CALGB 39904.

J Clin Oncol 2010 Jan 23;28(2):202-6. Epub 2009 Nov 23.

Department of Radiation Oncology, State University of New York Upstate Medical University, 750 E Adams St, Syracuse NY 13210, USA.

Purpose: The optimal treatment for medically inoperable stage I non-small-cell lung cancer (NSCLC) has not been defined.

Patients And Methods: Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced.

Results: Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients.

Conclusion: Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted.
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http://dx.doi.org/10.1200/JCO.2009.25.0753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2815709PMC
January 2010

Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial.

Lancet 2009 Aug 24;374(9687):379-86. Epub 2009 Jul 24.

Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153-5589, USA.

Background: Results from phase II studies in patients with stage IIIA non-small-cell lung cancer with ipsilateral mediastinal nodal metastases (N2) have shown the feasibility of resection after concurrent chemotherapy and radiotherapy with promising rates of survival. We therefore did this phase III trial to compare concurrent chemotherapy and radiotherapy followed by resection with standard concurrent chemotherapy and definitive radiotherapy without resection.

Methods: Patients with stage T1-3pN2M0 non-small-cell lung cancer were randomly assigned in a 1:1 ratio to concurrent induction chemotherapy (two cycles of cisplatin [50 mg/m(2) on days 1, 8, 29, and 36] and etoposide [50 mg/m(2) on days 1-5 and 29-33]) plus radiotherapy (45 Gy) in multiple academic and community hospitals. If no progression, patients in group 1 underwent resection and those in group 2 continued radiotherapy uninterrupted up to 61 Gy. Two additional cycles of cisplatin and etoposide were given in both groups. The primary endpoint was overall survival (OS). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00002550.

Findings: 202 patients (median age 59 years, range 31-77) were assigned to group 1 and 194 (61 years, 32-78) to group 2. Median OS was 23.6 months (IQR 9.0-not reached) in group 1 versus 22.2 months (9.4-52.7) in group 2 (hazard ratio [HR] 0.87 [0.70-1.10]; p=0.24). Number of patients alive at 5 years was 37 (point estimate 27%) in group 1 and 24 (point estimate 20%) in group 2 (odds ratio 0.63 [0.36-1.10]; p=0.10). With N0 status at thoracotomy, the median OS was 34.4 months (IQR 15.7-not reached; 19 [point estimate 41%] patients alive at 5 years). Progression-free survival (PFS) was better in group 1 than in group 2, median 12.8 months (5.3-42.2) vs 10.5 months (4.8-20.6), HR 0.77 [0.62-0.96]; p=0.017); the number of patients without disease progression at 5 years was 32 (point estimate 22%) versus 13 (point estimate 11%), respectively. Neutropenia and oesophagitis were the main grade 3 or 4 toxicities associated with chemotherapy plus radiotherapy in group 1 (77 [38%] and 20 [10%], respectively) and group 2 (80 [41%] and 44 [23%], respectively). In group 1, 16 (8%) deaths were treatment related versus four (2%) in group 2. In an exploratory analysis, OS was improved for patients who underwent lobectomy, but not pneumonectomy, versus chemotherapy plus radiotherapy.

Interpretation: Chemotherapy plus radiotherapy with or without resection (preferably lobectomy) are options for patients with stage IIIA(N2) non-small-cell lung cancer.

Funding: National Cancer Institute, Canadian Cancer Society, and National Cancer Institute of Canada.
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http://dx.doi.org/10.1016/S0140-6736(09)60737-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407808PMC
August 2009

The thrill of victory; the agony of defeat.

Authors:
Andrew T Turrisi

Int J Radiat Oncol Biol Phys 2008 Apr;70(5):1300-2

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http://dx.doi.org/10.1016/j.ijrobp.2007.12.035DOI Listing
April 2008

Evidence for management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).

Chest 2007 Sep;132(3 Suppl):314S-323S

Technology Evaluation Center, Blue Cross Blue Shield Association, 1310 G St, NW, Washington, DC 20005, USA.

Purposes: This systematic review addressed the following key questions on managing small cell lung cancer (SCLC): the sequence, timing, and dosing characteristics of primary thoracic radiotherapy (TRTx) for limited-stage disease; primary TRTx for extensive-stage disease; effect of prophylactic cranial irradiation (PCI); positron emission tomography (PET) for staging; treatment of mixed histology tumors; surgery; and second-line and subsequent-line treatment for relapsed/progressive disease.

Methods: The review methods were defined prospectively in a written protocol. We primarily sought randomized controlled trials that compared the interventions of interest.

Results: Robust evidence was lacking for all questions except PCI, for which a patient-level metaanalysis showed that PCI improves survival of SCLC patients who achieved complete response after primary therapy from 15.3 to 20.7% (p = 0.01). The case for concurrent over sequential radiation delivery rests largely on a single multicenter trial. Support for early concurrent therapy comes from one multicenter trial, but two other multicenter trials found no advantage. Metaanalysis did not find significant reductions in 2-year and 3-year mortality rates for early TRTx. Favorable results from a single-center trial on TRTx for extensive stage disease need replication in a multicenter setting. Relevant comparative studies were nonexistent for management of mixed histology disease and surgery for early limited SCLC. PET may be more sensitive in detecting extracranial disease than conventional staging modalities, but studies were of poor quality.

Conclusions: PCI improves survival among those with a complete remission to primary therapy. A research agenda is needed to optimize the effectiveness of TRTx and its components.
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http://dx.doi.org/10.1378/chest.07-1384DOI Listing
September 2007

A review of first-line treatment for small-cell lung cancer.

J Thorac Oncol 2006 Mar;1(3):270-8

University of British Columbia, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

Although small-cell lung cancer (SCLC) makes up a smaller proportion of all lung cancers than it did 25 years ago, it remains a common cause of cancer mortality that requires more clinical and basic research than is currently underway. Trials of newer chemotherapy variations have failed to produce a regimen that is clearly superior to the two-drug combination of etoposide and cisplatin, which remains the standard of care for both limited and extensive stage SCLC. Paradoxically, advances in this systemic disease have come from radiotherapy innovations for limited SCLC, including addition of thoracic irradiation to systemic chemotherapy, more intense thoracic irradiation, early integration of thoracic irradiation with systemic chemotherapy, and prophylactic cranial irradiation.
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http://dx.doi.org/10.1016/s1556-0864(15)31579-3DOI Listing
March 2006

Conformal high dose external radiation therapy, 80.5 Gy, alone for medically inoperable non-small cell lung cancer: a retrospective analysis.

J Thorac Oncol 2006 Feb;1(2):112-9

Department of Radiation Oncology, Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina 27157, USA.

Background: Retrospective analysis of patients with medically inoperable non-small cell lung cancer treated with continuous high-dose external beam radiation therapy at the Medical University of South Carolina.

Methods: We identified 35 patients with non-small cell lung cancer treated 1998-2002. None were candidates for resection for reasons including: pulmonary function (n = 23), previous cancer (n = 9), other co-morbidities (n = 2), and refusal of surgery (n = 1). Median percent predicted forced expiratory volume in 1 second was 41.5%. Median age was 71 years. Five patients had more than one primary tumor: three were concurrently treated, two were sequentially treated. Lesion sizes were <3 cm (n = 24); 3-5 cm (n = 12), and >5 cm (n = 5). Nodal stage was as follows: N0 (n = 33) and N1 (n = 2). Radiation therapy was administered once daily: median dose was 80.5 Gy/35 fx/2.3 Gy/fx. The clinical target volume was tumor plus nodes > or =1.0 cm. V20 data were available for 12 patients, with a mean value of 15.7%.

Results: Thirty-four patients completed treatment. Median follow-up was 23.0 months. There were 26 deaths: 19 died from non-small cell lung (73%) and seven died from co-morbid illness (27%). Median survival was 24 months (95% CI, 18.0-31.9 months). Four patients were alive with disease, and five were alive disease-free at 10- and 68-month follow-ups. Of 41 lesions, local failure occurred in 15 lesions (37%) of which 3 local failure patients (9%) failed concomitantly in untreated regional lymph nodes. There were no isolated nodal recurrences. Distant progression: 10 patients (29%) of which 6 distant progression without local failure. Two patients who both had prior lobectomies experienced grade 5 toxicities.

Conclusion: Continuous high-dose external beam radiation therapy 80.5 Gy administered in 35 fractions was tolerated. Treatment-related death was rare (6%) and isolated to patients with prior lobectomies in an extremely high-risk population. Most mortality was lung cancer-related. The dose of 80.5 Gy in 7 weeks is supported for patients with single lesions and no prior lobectomy. Local failure dominates and higher effective doses should be explored.
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February 2006

Scalpels, beams, drugs, and dreams: challenges of stage IIIA-N2 non-small-cell lung cancer.

J Natl Cancer Inst 2007 Mar;99(6):415-8

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http://dx.doi.org/10.1093/jnci/djk107DOI Listing
March 2007

Southwest Oncology Group: two decades of experience in non-small cell lung cancer.

Semin Oncol 2005 Apr;32(2 Suppl 3):S119-21

Department of Radiation Oncology, Karmanos Cancer Center, Wayne State University, 540 E. Canfield, 1212 Scott Hall, Detroit, MI 48201, USA.

Over the past two decades, studies of the Southwest Oncology Group have consistently reported stable esophagitis rates despite changing scales with concurrent chest radiotherapy and cisplatin/etoposide regimens. Patient selection has perhaps contributed to increased survival over this period. The Southwest Oncology Group has incorporated surgical questions and advanced the field with a steady use of consistent therapies (ie, cisplatin/etoposide plus radiotherapy of 45 Gy [induction therapy] and cisplatin/etoposide plus at least 61 Gy) in potentially operable or unresectable disease. Further studies examining the addition of either docetaxel or novel agents to such regimens are underway.
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http://dx.doi.org/10.1053/j.seminoncol.2005.03.022DOI Listing
April 2005

A case against surgery for most IIIa non-small cell lung cancer.

Authors:
Andrew T Turrisi

Semin Oncol 2005 Apr;32(2 Suppl 3):S6-8

Department of Radiation Oncology, Karmanos Cancer Center, Wayne State University, 540 E. Canfield, 1212 Scott Hall, Detroit, MI 48201, USA.

Stage IIIa non-small cell lung cancer remains categorically a heterogeneous hodgepodge without clear prospective mandates for clinical care. Poor outcome ensues for patients with mediastinal node-positive cancer when treated with surgery alone, but we are unclear how to define subsets that might benefit from surgery. This article reviews significant trials of surgery and chemoradiotherapy, including those using induction chemotherapy for stage III patients. While many continue to believe that chemotherapy without RT may provide equivalent pathologic complete response and survival rates, there is very little apparent difference in survival between patients managed with surgery or those managed to a higher dose of radiotherapy with concurrent chemotherapy (using an established chemotherapy regimen, 2-dimensional radiotherapy treatment planning, and a dose of only 61 Gy). If there is any benefit to surgery in the IIIa as currently staged, the benefit is very small and is counterbalanced by operative risk.
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http://dx.doi.org/10.1053/j.seminoncol.2005.03.003DOI Listing
April 2005

Creeping phase II-ism and the medical pharmaceutical complex: weapons of mass distraction in the war against lung cancer.

Authors:
Andrew T Turrisi

J Clin Oncol 2005 Aug 6;23(22):4827-9. Epub 2005 Jun 6.

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http://dx.doi.org/10.1200/JCO.2005.02.904DOI Listing
August 2005

Outcome of radiation therapy for renal transplant rejection refractory to chemical immunosuppression.

Radiother Oncol 2005 Jan;74(1):17-9

Department of Radiation Oncology, Medical University of South Carolina, 169 Ashley Avenue, Charleston, SC 29425, USA.

Twenty consecutive patients with kidney graft rejection refractory to chemical immunosuppression were treated with local irradiation to the transplanted renal graft (3 x 1.5 Gy). Ten patients were complete responders (median follow-up: 47 months). Six patients were partial responders and failed after 1-4 months. Four patients did not respond.
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http://dx.doi.org/10.1016/j.radonc.2004.08.011DOI Listing
January 2005

National Institutes of Health State-of-the-Science Conference Statement: Symptom management in cancer: pain, depression, and fatigue, July 15-17, 2002.

J Natl Cancer Inst Monogr 2004 (32):9-16

Background: Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. STATE-OF-THE-SCIENCE PROCESS: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet. The panel's final statement is available at http://consensus.nih.gov.

Conclusions: The panel concluded that the available evidence supports a variety of interventions for treating cancer patients' pain, depression, and fatigue. Clinicians should routinely use brief assessment tools to ask patients about pain, depression, and fatigue and to initiate evidence-based treatments. Assessment should include discussion about common symptoms experienced by cancer patients, and these discussions should continue over the duration of the illness. Impediments to effective symptom management in cancer patients can arise from different sources and interactions among providers, patients and their families, and the health care system. Numerous factors could interfere with adequate symptom management. Among these factors are incomplete effectiveness of some treatments, a lack of sufficient knowledge regarding effective treatment strategies, patient reluctance to report symptoms to caregivers, a belief that such symptoms are simply a part of the cancer experience that must be tolerated, and inadequate coverage and reimbursement for some treatments. Additional research is needed on the definition, occurrence, the treatment of pain, depression, and fatigue, alone and in combination, in adequately funded prospective studies. The panel also concluded that the state of the science in cancer symptom management should be reassessed periodically.
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http://dx.doi.org/10.1093/jncimonographs/djg014DOI Listing
January 2005

Limited-disease small-cell lung cancer research: sense and nonsense.

Authors:
Andrew T Turrisi

Int J Radiat Oncol Biol Phys 2004 Jul;59(4):925-7

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http://dx.doi.org/10.1016/j.ijrobp.2004.02.054DOI Listing
July 2004

Small cell lung cancer: state of the art and future perspectives.

Lung Cancer 2004 Jul;45(1):105-17

Multidisciplinary Oncology Center, University Hospital CHUV, 46, Rue du Bugnon, 1011 Lausanne, Switzerland.

Small cell lung cancer accounts for less than 20% of all lung cancer. The management of this distinct tumor entity differs from the more common non-small cell lung cancer. Primary prevention of smoking exposure remains the most important public health measure. Although small cell lung is an exquisitely chemosensitive disease it remains ultimately fatal for the great majority of patients. Combination chemotherapy regimens have improved response rate and survival of the last three decades. The combination of cisplatin and etoposide has been considered the standard therapy for over a decade. More intensive triplet combination chemotherapy and high-dose chemotherapy have shown improved response rates and survival. Early concomitant and accelerated radiotherapy improves survival in limited stage disease. This review summarizes the current state of the art and future perspectives in detection, staging and standard therapy of small cell lung cancer. Particular emphasis is given to the importance of concomitant and accelerated radiotherapy and consideration of dose-intensive combination chemotherapy regimens.
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http://dx.doi.org/10.1016/j.lungcan.2003.12.006DOI Listing
July 2004

70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808.

Int J Radiat Oncol Biol Phys 2004 Jun;59(2):460-8

Department of Radiation Oncology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.

Purpose: To prospectively evaluate the feasibility of delivering 70 Gy once-daily thoracic radiotherapy (TRT), concurrent with chemotherapy, in the treatment of limited-stage small-cell lung cancer (L-SCLC).

Materials And Methods: Eligible patients received two cycles of induction paclitaxel (175 mg/m(2) on Day 1) and topotecan (1 mg/m(2) on Days 1-5) with granulocyte colony stimulating factor support, followed by three cycles of carboplatin (area under the curve = 5 on Day 1) and etoposide (100 mg/m(2) on Days 1-3). TRT (70 Gy, 2 Gy/fx/7 weeks) was initiated with the first cycle of carboplatin and etoposide. Prophylactic cranial irradiation was offered to patients achieving a complete response or good partial response.

Results: Ninety percent of patients (57 of 63) proceeded to protocol TRT. There was one treatment-related fatality. Nonhematologic Grade 3/4 toxicities affecting more than 10% of patients, during or after TRT, were dysphagia (16%/5%) and febrile neutropenia (12%/4%). The response rate to all therapy was 92% and the median overall survival is 22.4 months (95% confidence interval 16.1, infinity ). Twenty-eight patients remain alive with a median follow-up of 24.7 months.

Conclusion: 70 Gy once-daily TRT can be delivered safely in the cooperative group setting for patients with L-SCLC. Initial efficacy data are encouraging. The hypothesis that high-dose once-daily TRT results in comparable or improved survival compared with twice-daily accelerated TRT warrants testing in a Phase III trial.
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http://dx.doi.org/10.1016/j.ijrobp.2003.10.021DOI Listing
June 2004

American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003.

J Clin Oncol 2004 Jan 22;22(2):330-53. Epub 2003 Dec 22.

American Society of Clinical Oncology, Cancer Policy and Clinical Affairs, 1900 Duke St, Suite 200, Alexandria, VA 22314, USA.

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http://dx.doi.org/10.1200/JCO.2004.09.053DOI Listing
January 2004

Novel doublets in extensive-stage small-cell lung cancer: a randomized phase II study of topotecan plus cisplatin or paclitaxel (CALGB 9430).

Clin Lung Cancer 2002 Feb;3(3):205-10; discussion 211-2

Missouri Baptist Medical Center, St. Louis, MO 63131, USA.

Chemotherapy for extensive-stage small-cell lung cancer (E-SCLC) produces high response rates and improved survival but few cures. We tested three new regimens for E-SCLC that might merit further investigation in a subsequent phase III trial. Cancer and Leukemia Group B 9430 was a randomized phase II study evaluating 4 treatment arms in 57 evaluable, previously untreated E-SCLC patients. Each arm consisted of the following: Arm 1: cisplatin plus topotecan; Arm 2: cisplatin plus paclitaxel; Arm 3: paclitaxel 230 mg/m2 plus topotecan; and Arm 4: paclitaxel 175 mg/m2 plus topotecan. Because of an accrual time difference, Arm 2 will not be discussed in this manuscript. Arm 1 (12 patients) produced 1 complete response (CR, 8%) and an overall response rate (ORR) of 42%. Toxicity was excessive, with 3 deaths (25%). Arm 3 (13 patients) produced no CRs, 7 partial responses (PRs, 54%), median survival of 13.8 months, and failure-free survival (FFS) of 7.41 months, with 3 toxic deaths (25%). Among 32 evaluable patients on Arm 4, there were 2 CRs (6%) and 20 PRs (63%) for an ORR of 69%, median survival of 9.9 months, FFS of 5.21 months, and 1-year survival of 40%. There was 1 possible treatment-related death (3%). Topotecan plus cisplatin, in the doses and schedule employed, produced excessive toxicity and modest efficacy in E-SCLC patients. Paclitaxel (230 mg/m2 on day 1) plus topotecan (1 mg/m2 on days 1-5) produced excessive toxicity that was ameliorated with an attenuated paclitaxel dose (175 mg/m2). With the latter regimen (Arm 4) in patients with a performance status of 0/1, CR rates, FFS, overall survival, and 1-year survival were similar to standard etoposide plus cisplatin chemotherapy. Further exploration of topoisomerase inhibitors and taxanes in SCLC patients is warranted.
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http://dx.doi.org/10.3816/clc.2002.n.004DOI Listing
February 2002

Lunx is a superior molecular marker for detection of non-small cell lung cancer in peripheral blood [corrected].

J Mol Diagn 2003 Nov;5(4):237-42

Departments of Surgery, Pulmonary and Critical Care Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

The clinical management of non-small cell lung cancer (NSCLC) would benefit greatly by a test that was able to detect small amounts of NSCLC in the peripheral blood. In this report, we used a novel strategy to enrich tumor cells from the peripheral blood of 24 stage I to IV NSCLC patients and determined expression levels for six cancer-associated genes (lunx, muc1, KS1/4, CEA, CK19, and PSE). Using thresholds established at three standard deviations above the mean observed in 15 normal controls, we observed that lunx (10 of 24, 42%), muc1 (5 of 24, 21%), and CK19 (5 of 24, 21%) were overexpressed in 14 of 24 (58%) peripheral blood samples obtained from NSCLC patients. Patients who overexpressed either KS1/4 (n = 2) or PSE (n = 1) also overexpressed either lunx or muc1. Of patients with presumed curable and resectable stage I to II disease (n = 7), at least one marker was overexpressed in three (43%) patients. In advanced stage III to IV patients (n = 17), at least one marker was overexpressed in 11 patients (65%). These results provide evidence that circulating tumor cells can be detected in NSCLC patients by a high throughput molecular technique. Further studies are needed to determine the clinical relevance of gene overexpression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1907342PMC
http://dx.doi.org/10.1016/s1525-1578(10)60480-1DOI Listing
November 2003

Report from the Radiation Oncology Committee of the Southwest Oncology Group (SWOG): Research Objectives Workshop 2003.

Am J Clin Oncol 2003 Oct;26(5):522-9

Department of Radiation Oncology, JP Wilmot Cancer Center, University of Rochester, Rochester, NY 14642, USA.

To achieve the ultimate goal of cancer treatment, which is 100% cancer control with negligible toxicity, the therapeutic window must be enlarged, allowing for higher doses of beneficial treatments with reduced toxicity. The advent of image- and metabolism-guided therapy offers the best opportunity to date for combining modern radiation targeting and imaging techniques. Indeed, for the first time, it is reasonable to locally target metastatic disease with the goal of sterilization. Combining these focal radiation techniques with novel targeted antiproliferative agents and full-dose classic cytotoxic chemotherapy will become more effective as we learn to use these compounds in a less systemically toxic manner and as radiation fields become more defined. In addition, increasing numbers of biologic modifiers of normal tissue response are becoming available, and they suggest great promise for decreasing the normal tissue toxicity resulting from both radiation and chemotherapy treatments. Thus, radiation metastectomy for gross metastases, used together with systemic control of micrometastatic disease, may yield improved survival rates. This hypothesis is ready for testing in cancers of the breast, prostate, colon, and in sarcomas. Enlarging the therapeutic window is a major goal that would allow for an increasingly favorable therapeutic gain.
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http://dx.doi.org/10.1097/01.coc.0000092253.71406.2bDOI Listing
October 2003

The role of radiotherapy and chemotherapy for curative management of medically inoperable and stage III nonsmall cell lung cancer, and radiotherapy for palliation of symptomatic disease.

Respir Care Clin N Am 2003 Jun;9(2):163-90

Department of Radiation Oncology, Medical University of South Carolina, P.O. Box 250318, Charleston, SC 29425, USA.

Radiotherapy has an expanding role in all phases of treatment of nonsmall cell lung cancer. Evolutions in technique, such as three-dimensional conformal radiotherapy, hold the promise for more effective treatment of patients with early stage disease who are not candidates for surgical intervention. Multimodality therapy for patients with locally advanced disease is evolving rapidly, with evidence accruing as to the optimal schedules and doses of radiotherapy and combination chemotherapy. Palliative dose schedules are being refined that maximize patient comfort while providing substantial symptom relief.
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http://dx.doi.org/10.1016/s1078-5337(02)00087-4DOI Listing
June 2003

National Institutes of Health State-of-the-Science Conference Statement: Symptom Management in Cancer: Pain, Depression, and Fatigue, July 15-17, 2002.

J Natl Cancer Inst 2003 Aug;95(15):1110-7

Department of Health Services, University of Washington, Seattle, WA, USA.

Background: Despite advances in early detection and effective treatment, cancer remains one of the most feared diseases. Among the most common side effects of cancer and treatments for cancer are pain, depression, and fatigue. Although research is producing increasingly hopeful insights into the causes and cures for cancer, efforts to manage the side effects of the disease and its treatments have not kept pace. The challenge that faces us is how to increase awareness of the importance of recognizing and actively addressing cancer-related distress. The National Institutes of Health (NIH) convened a State-of-the-Science Conference on Symptom Management in Cancer: Pain, Depression, and Fatigue to examine the current state of knowledge regarding the management of pain, depression, and fatigue in individuals with cancer and to identify directions for future research. Specifically, the conference examined how to identify individuals who are at risk for cancer-related pain, depression, and/or fatigue; what treatments work best to address these symptoms when they occur; and what is the best way to deliver interventions across the continuum of care. State-of-the-Science Process: A non-advocate, non-Federal, 14-member panel of experts representing the fields of oncology, radiology, psychology, nursing, public health, social work, and epidemiology prepared the statement. In addition, 24 experts in medical oncology, geriatrics, pharmacology, psychology, and neurology presented data to the panel and to the conference audience during the first 1.5 days of the conference. The panel then prepared its statement, addressing the five predetermined questions and drawing on submitted literature, the speakers' presentations, and discussions held at the conference. The statement was presented to the conference audience, followed by a press conference to allow the panel to respond to questions from the media. After its release at the conference, the draft statement was made available on the Internet. The panel's final statement is available at http://consensus.nih.gov.

Conclusions: The panel concluded that the available evidence supports a variety of interventions for treating cancer patients' pain, depression, and fatigue. Clinicians should routinely use brief assessment tools to ask patients about pain, depression, and fatigue and to initiate evidence-based treatments. Assessment should include discussion about common symptoms experienced by cancer patients, and these discussions should continue over the duration of the illness. Impediments to effective symptom management in cancer patients can arise from different sources and interactions among providers, patients and their families, and the health care system. Numerous factors could interfere with adequate symptom management. Among these factors are incomplete effectiveness of some treatments, a lack of sufficient knowledge regarding effective treatment strategies, patient reluctance to report symptoms to caregivers, a belief that such symptoms are simply a part of the cancer experience that must be tolerated, and inadequate coverage and reimbursement for some treatments. Additional research is needed on the definition, occurrence, the treatment of pain, depression, and fatigue, alone and in combination, in adequately funded prospective studies. The panel also concluded that the state of the science in cancer symptom management should be reassessed periodically.
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http://dx.doi.org/10.1093/jnci/djg014DOI Listing
August 2003

Docetaxel-based combined-modality chemoradiotherapy for locally advanced non-small cell lung cancer.

Oncologist 2003 ;8(4):361-74

University of Turin, Department of Clinical and Biological Sciences, S. Luigi Hospital, Thoracic Oncology Unit, Torino, Italy.

The cytotoxic agent docetaxel not only has proven activity in non-small cell lung cancer-when used alone or in combination-but is also a potent radiosensitizer, and improved treatments are needed in all stages of this disease. In patients with locoregionally advanced (stage III) disease, docetaxel has shown efficacy with manageable toxicities when used alone or in combination with a platinum compound in a sequential manner before localized radical radiotherapy/surgery. Presently, therapeutic gains appear to be maximized by the use of concurrent chemotherapy and irradiation. This review focuses on research with combinations of docetaxel with either cisplatin or carboplatin and radiotherapy. Overall response and survival rates to date provide data worth pursuing. From phase I data, weekly docetaxel at 20 mg/m(2) plus cisplatin at 25 mg/m(2) or carboplatin to an area under the concentration time curve of 2 mg/ml*min with concurrent radiotherapy to 60 Gy over 6 weeks appear to be suitable for phase II trials. Predominant toxicities are esophagitis and neutropenia, but a low frequency of pulmonary toxicity is reported. Induction, concurrent, and consolidation docetaxel-based chemoradiotherapy in potentially resectable disease are all being investigated. Future research could include the investigation of computed tomography/ positron emission tomography-derived target volume radiotherapy, dose-escalated therapy, and alternative fractionation schedules in combination with docetaxel-based cytotoxic chemotherapy.
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http://dx.doi.org/10.1634/theoncologist.8-4-361DOI Listing
December 2003

Limited stage small cell lung cancer: treatment and therapy.

Authors:
Andrew T Turrisi

Curr Treat Options Oncol 2003 Feb;4(1):61-4

Department of Radiation Oncology, Medical University of South Carolina, 169 Ashley Avenue, PO Box 250318, Charleston, SC 29425, USA.

Chemotherapy remains the key treatment for small cell lung cancer; today, that chemotherapy remains cisplatin and etoposide in a variety of acceptable schedules. Attempts to use new drugs in extensive disease have not been as successful as hoped; however, a recent trial from Japan supports the use of irinotecan and cisplatin over the standard cisplatin and etoposide, but these facts need to be verified in western countries. For limited disease, the addition of thoracic radiotherapy for all patients and prophylactic cranial irradiation (PCI) in complete, or near complete, responders have resulted in improved survival. The best results occur with early, intensive thoracic radiotherapy concurrent with chemotherapy and PCI after completion of systemic and local therapy. The use of PCI and thoracic radiotherapy in extensive disease is more controversial and less evidence based. PCI and thoracic radiotherapy may be considered only in patients who have achieved a "systemic" complete response and excellent response in the chest. However, both prospects should be supported if there is complete response systemically and near complete response locally. The role of surgery is of limited value in the unusual cases of mediastinal negative disease, but it is a good treatment for patients with peripheral nodules and sufficient pulmonary function to withstand thoracotomy.
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http://dx.doi.org/10.1007/s11864-003-0032-9DOI Listing
February 2003

The new drugs and biologics as sensitizers in the treatment of non-small cell lung cancer.

Authors:
Andrew T Turrisi

Suppl Tumori 2002 Jul-Aug;1(4):S55-7

Department of Radiation Oncology, Medical University of South Carolina, Charleston, USA.

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November 2002

Locally advanced esophageal cancer.

Curr Treat Options Oncol 2002 Dec;3(6):475-85

Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas Street, Charleston, SC 29425, USA.

Patients diagnosed with adenocarcinoma or squamous cell carcinoma of the esophagus should undergo computed tomography of the chest and abdomen and positron emission tomography to look for evidence of distant metastatic disease. In the absence of systemic metastases, locoregional staging should be performed with endoscopic ultrasonography and fine needle aspiration of accessible periesophageal lymph nodes and any detectable celiac lymph nodes. Patients found to have T3 tumors (transmural extension), T4 tumors (invasion of adjacent structures), or N1-M1a (lymph node-positive) disease do poorly when treated with surgery alone; 5-year survival is less than 20%. These patients should be considered for combined modality therapy. Patients with T4 disease are generally not deemed candidates for surgical resection; they may be considered for definitive chemoradiotherapy. Patients with T3 disease or lymph node-positive disease may be treated with neoadjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy alone. Patients considered for trimodality therapy should be fully restaged before surgery to assess their response to neoadjuvant treatment. This should include repeat endoscopic ultrasound and fine needle aspiration of lymph nodes. Patients whose lymph node metastases do not completely respond to neoadjuvant therapy are unlikely to benefit from the addition of surgery. Patients with persistently positive celiac lymph nodes have a very poor prognosis and should not undergo surgery. Patients with persistent nodal disease who have good performance status may be considered for additional chemotherapy. Patients with locally advanced esophageal cancer who have poor performance status are not good candidates for combined modality therapy. These individuals are best managed with palliative intent. Particular attention should be given to alleviating the common problem of dysphagia, which causes significant morbidity.
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http://dx.doi.org/10.1007/s11864-002-0067-3DOI Listing
December 2002

Dose-volume relationship for acute side effects during high dose conformal radiotherapy for prostate cancer.

Radiother Oncol 2002 Aug;64(2):209-14

Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium.

Purpose: To determine acute and late complications for bladder and rectum and to determine dose-volume correlations.

Methods And Materials: Sixty-four patients received definitive treatment for prostate cancer between January 1995 and December 1998 using conformal three-dimensional radiotherapy. Doses ranged from 72 to 80Gy. The acute and late side effects were gathered retrospectively, and graded according to Radiotherapy and Oncology Group criteria (RTOG). The patients were divided into two groups: or=76Gy (Group B) and had a mean follow-up of 32 and 22 months, respectively.

Results: No grades 3-4 acute, urinary or rectal toxicity was reported. Acute grade 2 rectal complications were seen in 10 and 18% of the patients in Groups A and B, respectively. They were observed at a mean dose of 38Gy. Acute grade 2 urinary symptoms were 33 and 47% for Groups A and B, respectively. They were seen at a mean dose of 43Gy. Acute rectal symptoms were dose-volume related. Patients without diarrhea had a mean rectal volume receiving a dose of 70Gy or more of 8.5 cm(3). However, patients with RTOG 2 diarrhea had a volume of 16.5 cm(3) (P=0.042). No dose-volume relationship for acute bladder symptoms or late complications were seen. Grades 1-2 late rectal and bladder complications were seen in 11 and 8% of the patients, respectively. None required hospital admission or transfusion.

Conclusion: Radiotherapy to the prostate can be given at 80Gy. No grades 3-4 acute, urinary or rectal toxicity was reported. Acute rectal symptoms are dose-volume related.
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http://dx.doi.org/10.1016/s0167-8140(02)00185-8DOI Listing
August 2002