Academia.edu no longer supports Internet Explorer.
To browse Academia.edu and the wider internet faster and more securely, please take a few seconds to upgrade your browser.
2015
…
6 pages
1 file
Locally advanced non-small cell lung cancer (LA-NSCLC) is typically treated with thoracic radiotherapy, often in combination with cytotoxic chemotherapy. Despite tremendous advances in the evaluation, treatment techniques, and supportive care measures provided to LA-NSCLC patients, local disease progression and distant metastases frequently develop following definitive therapy. A recent landmark randomized trial demonstrated that radiotherapy dose escalation may reduce survival rates, highlighting our poor understanding of the effects of thoracic radiotherapy for LA-NSCLC. Here, we present rationale for further studies of radiotherapy dose escalation as well as arguments for exploring relatively low radiotherapy doses for LA-NSCLC.
2001
Surgery is the preferred and standard treatment for patients with resectable stage I and II non-small cell lung cancer (NSCLC). Survival rates of local surgery are unbeaten by other treatment modalities. Up to 70% of these patients survive 5 years or longer. However, there is a subset of patients who either are inoperable due to the presence of severe associated diseases, or who refuse surgery. In these patients radical radiotherapy with curative intent is an effective alternative. In our department we retrospectively analysed survival and freedom from treatment failure in those patients treated in our hospital with primary irradiation for stage I and II NSCLC (T1-2 N0-1 M0) during the last 20 years. In total 60 patients with a median age of 69 years could be evaluated. 35% had stage I and 65% had stage II NSCLC. All patients received 2-or 3-dimensionally planned megavoltage radiotherapy with a median dose of 60 Gy with normally fractionated single doses of 2.0 Gy five times a week. Pneumonitis WHO Grade III was found in 5 out of the 60 patients (8.3%). Locoregional recurrence was observed in 53% of the patients resulting in a median progression-free survival of 18 months and a median overall survival of 20.5 months. However, there is a need for further improvement of treatment outcome of radiotherapy for medically inoperable patients with early-stage NSCLC. One possibility might be radiation dose escalation or alteration in fractionation of radiotherapy, such as continuous hyperfractionated accelerated radiotherapy CHART or a modification thereof CHARTWEL. These new fractionation schemes might be beneficial for a subset of patients in terms of improved local control, reduced incidence of metastasis and improved long term survival. The combination of chemotherapy and radiotherapy might be another option for treatment of early-stage NSCLC. In advanced disease combined modality treatment turned out to be superior to radiotherapy alone, concerning local control and survival. If this is true also for early-stage NSCLC, it has to be shown in further investigations.
International Journal of Radiation Oncology Biology Physics, 1999
>70) is induction chemotherapy followed by definitive radiotherapy to the primary site at 1.8 -2.0 Gy per fraction with a total dose of 60 -63 Gy to the target volume. Patients with poor prognostic factors usually receive radiotherapy alone, but the fractionation schedule and total dose have not been standardized. To attempt to optimize irradiation doses and schedule, we compared the effectiveness of accelerated radiotherapy (ACRT) alone to 45 Gy at 3 Gy per fraction with standard radiation therapy (STRT) of 60 -66 Gy at 2 Gy per fraction in regard to tumor response, local control, distant metastasis, toxicity, and survival. Methods and Materials: Fifty-five patients treated with radiation for NSCLC at The University of Texas M. D. Anderson Cancer Center between 1990 and 1994 were identified. All 55 patients had node-positive, and no distant metastasis (N؉, M0) of NSCLC. Two cohorts were identified. One cohort (26 patients) had borderline poor prognostic factors (KPS less than 70 but higher than 50, and/or WL of more than 5%) and was treated with radiotherapy alone to 45 Gy over 3 weeks at 3 Gy/fraction (ACRT). The second cohort (29 patients) had significantly better prognostic factors (KPS >70 and WL <5%) and was treated to 60 -66 Gy over 6 to 6 1 2 weeks at 2 Gy per fraction (STRT) during the same period. Results: In the first cohort treated by ACRT, the distribution of patients by AJCC stage was IIB 8%, IIIA 19%, and IIIB 73%. Sixty-two percent had KPS <70, and 76% had a WL of >5%. The maximum response rate as determined by chest X-ray was 60% among 45 of 55 patients who were evaluable for response: combined complete responses (20%) and partial responses (40%). Overall survival in these patients was 13% at 2 and 5 years, with a locoregional control rate of 42% and a freedom from distant metastasis rate of 54%. The ACRT cohort treated with 3 Gy per fraction had significantly lower KPS scores (p ؍ 0.003) and greater WL (p ؍ 0.063) than the cohort STRT treated with 2 Gy per fraction. However, treatment results and toxicity were not significantly different between the two cohorts in spite of significantly better prognostic factors in the STRT cohort. Conclusions: Despite having worse prognostic factors, the cohort treated with radiotherapy alone to 45 Gy at 3 Gy per fraction over 3 weeks (ACRT) had response rates, locoregional control, and overall survival comparable to those in the cohort treated by a total dose of 60 -66 Gy at 2 Gy per fraction over 6 to 6 1 2 weeks (STRT). Given that accelerated treatment schedules decrease treatment time and cost less, these may, in the current health care environment, be important factors for health care providers to consider in treating patients who have locally advanced NSCLC and borderline poor prognostic factors. © 1999 Elsevier Science Inc.
Oncology & hematology review, 2010
Lung cancer is the leading cause of cancer deaths, having caused an estimated 1.18 million deaths worldwide in 2002. 1 In the US alone, lung cancer resulted in an estimated 159,300 deaths in 2009. 2 Most deaths are from non-small-cell lung cancer (NSCLC), which accounts for more than 80% of lung cancers diagnosed in the US. Sadly, most patients present with advanced, inoperable disease. While stage IV patients remain incurable, there is now potentially curative therapy that can be offered to most patients with stage III NSCLC. 3 Radiotherapy Becomes Standard Treatment for Unresectable Non-small-cell Lung Cancer Over 40 years ago, Wolf et al. established the role of RT in the treatment of lung cancer. Their randomized phase III trial compared radiotherapy (RT) versus placebo for clinically inoperable lung cancer (including both small-cell and NSCLC). RT was delivered with 200-250kV X-rays and included the delivery of 40-50Gy in 1.5-2.0Gy daily fractions. The median survival of patients given RT was 142 days compared with 112 days for those who received the placebo (p=0.05). 4 A phase III Radiation Therapy Oncology Group (RTOG) trial evaluated the effect of dose on outcome by randomly assigning patients to receive 40Gy in 20 daily fractions, 50Gy in 25 daily fractions, or 60Gy in 30 daily fractions. The local failure rates determined with serial chest X-rays were 48% with 40Gy, 38% with 50Gy, and 27% with 60Gy. Although the differences in survival were not significant, this study defined the standard RT dose as 60Gy in 30 daily fractions. 5 This dose fractionation pattern remained the standard of care for decades. Conventional RT alone resulted in a median survival of 10 months and a five-year survival of 5%. Until the 1990s, the standard treatment for locally advanced inoperable lung cancer was RT alone. 5 Combined Radiotherapy (RT) plus Chemotherapy Supplants RT Alone as Standard Therapy In order to improve the outcome of treatment, chemotherapy was added to RT. Phase III trials demonstrated a survival advantage following the addition of chemotherapy to RT for NSCLC. 6,7 The Cancer and Leukemia Group B reported that induction chemotherapy (cisplatin plus vinblastine) followed by conventional RT (60Gy/30 fractions) resulted in significantly better survival than conventional RT alone. 6 The median and five-year survivals were 13.7 months and 17% for the combined therapy versus 9.6 months and 6% for RT alone (p=0.012). 6 Additional phase III trials confirmed that cisplatin-based chemotherapy plus RT produced better survival rates than RT alone. 7-10 Subsequent phase III trials established that concurrent chemotherapy plus RT resulted in significantly better survival than sequential therapy. 11,12 Modern trials of concurrent chemotherapy plus RT have reported five-year survival rates of up to 29%. 13 Local Failures Remain a Significant Problem Local control rates based on radiographic studies appear substantially better than those based on pathological findings. Le Chevalier et al.
The Oncologist, 2008
After completing this course, the reader will be able to:
Journal of Thoracic Oncology, 2017
Introduction: This phase I/II trial was designed to determine the maximally tolerated dose of thoracic radiotherapy as part of a combined modality approach. This report includes the long-term outcomes of patients treated on this study. The phase II portion was never completed, as RTOG-0617 opened before it was concluded. Methods: In this study, the maximally tolerated dose was defined as 74 Gy of radiation in 37 fractions. Twenty-five patients with unresectable NSCLC were treated with 2-Gy daily fractions and concurrent weekly carboplatin and paclitaxel. Of these patients, 20 had stage III disease and five had stage I or II disease. Results: Patients were followed until death or for a minimum of 5 years in the case of survivors. The median and 5-year survivals were 42.5 months and 20% for all patients, 52.9 months and 40% in patients with stages I or II disease, and 39.8 months and 15% in patients with stage III disease. Conclusions: The median survival of the stage III patients was quite favorable. We believe that this may have been due to a robust central review program of radiotherapy plans before treatment, ensuring compliance with protocol guidelines along with very low exposure of the heart to radiotherapy. Further improvements in 5-year survival will likely require research on both systemic therapy and thoracic radiotherapy. Potential therapeutic modalities that may aid in these efforts include immunotherapy, targeted therapy, improved imaging, adaptive radiotherapy, simultaneous integrated boost techniques, novel dose fractionation regimens, and charged particle therapy.
Lung Cancer, 1991
Patients with lung cancer represent one of largest disease group in any radiotherapy department. For the vast majority (75%), treatment can only be palliative. The advanced state of tumom-s at presentation and commonly held belief that radiotherapy cannot compete with surgery in its curative potential has led to apathy amongst clinicians and paucity of information on effee tiveness. That radiotherapy can produce significant rates of long-term survival has been demonstrated by Smart and Hilton [l] and since by a few single institution reviews [2,3]. That irradiation is capable of tumour sterilisation has been shown by preoperative and pathological studies [4]. The disappointing survival results of randomised studies may be the result of a number of diverse factors [5,6]. To understand the perspectives of radiation we need to consider its aims together with tumour and host imposed limitations. Anatomical considerations Even with improved staging methods clinical detection greatly underestimates the true extent of spread. The most accurate studies are pathological [7,81 but they are numerically small and have sampling and selection problems. Despite these reservations it is generally accepted that lo-30% of patients with 'completely resected' NSCLC will have pathological evidence of residual tumour and in 17% of patients with squamous histology this would be local [7]. In a study of 77 patients dying following operation one third had local recurrence alone [8]. These early post-mortem studies share one drawback. Perioperative staging would be considered inadequate by present day standards and it is therefore difficult to relate patterns of recurrence to initial stage of disease. That prognosis and overall survival is closely related to TNM staging is well known 19,101. Using combination of pTNM and clinical data, relationship between tumour extent and patterns of subsequent failure can be assessed. Immerman [ill in a study of 99 completely resected pa
Journal of Cancer Research Updates, 2018
Extensive Stage Small Cell Lung Carcinoma (ES-SCLC) affects approximately 160,000 patients worldwide every year and their prognosis remains dismal [1,2]. Standard management for ES-SCLC focuses on the delivery of cytotoxic chemotherapy and traditionally, radiotherapy is reserved for palliation of symptoms [2]. For selected patients who are successfully down-staged to Limited Stage SCLC (LS-SCLC), thoracic radiotherapy (TRT) may be considered, if it is deemed safe and tolerable [2]. This management paradigm ignores the problem of intrathoracic tumor control, wherein 75% of patients harbor persistent intra-thoracic disease after initial chemotherapy and about 90% manifest intra-thoracic disease progression at 1 year after completing initial chemotherapy [3]. However, new data is emerging from large database analyses and trials exploring the role of TRT in ES-SCLC, which suggest an expanded role of TRT in patients with ES-SCLC. A Surveillance, Epidemiology, and End Results (SEER) database analysis of 10,150 ES-SCLC patients, classified and treated on the basis of the Veterans Administration Lung Study Group (VALSG) definition between 1988 to 1997, was recently reported by Mahmoud et al. [4]. In this analysis, patients with disease confined to thorax only, without distant metastases (T-ESCLC) had significantly better 2yr overall survival (OS) when TRT was delivered (13% vs 4.1%, p < 0.001). Even patients with distant metastases (M-SCLC) had significantly better 2yr OS when TRT was delivered (4.4% vs 2.8%, p < 0.001) and TRT improved the 2yr OS of the entire study cohort from 2.5% to 6% as well as median OS from 4 months to 7 months (p < 0.001). Similarly, Whole Brain
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2017
This phase I/II trial was originally designed to determine the maximally tolerated dose(MTD) of thoracic radiotherapy(TRT) as part of a combined modality approach. This report includes the long-term outcome of patients treated on this study. The phase II portion was never completed as RTOG-0617 opened before it was concluded. The MTD was defined as 74Gy in 37 fractions in this study. Twenty-five patients with unresectable non-small cell lung cancer(NSCLC) were treated with 2Gy daily fractions and concurrent weekly carboplatin and paclitaxel. Of these, twenty had stage III disease and 5 had stages I-II disease. Patients were followed until death or for a minimum of 5 years in survivors. Median and 5-year survival were 42.5 months and 20% for all patients, 52.9 months and 40% in patients with stages I/II disease, and 39.8 months and 15% in patients with stage III disease. The median survival of the stage III patients was quite favorable. We believe that this may have been due to a rob...
Clinical Oncology, 2009
In this overview we review and model how radiotherapy tumour control and complication rates vary with dose, fractionation, schedule duration, irradiated volume and use of chemotherapy for stage III non-small cell lung cancer (NSCLC), and use the modelling to study the effectiveness of different NSCLC dose-escalation approaches being developed in the UK. Data have been collated for pneumonitis, lung fibrosis, early and late oesophagitis, cord and cardiac complications, and local progression-free survival at 30 months. Dependences of the various end points on treatment-related factors are catalogued and analysed using the linear-quadratic incomplete repair model to account for dose and fractionation effects, making linear corrections for differences in schedule duration, and loosely characterising volume effects using parallel-and series-type concepts. Tolerance limits are calculated for the different end points and distilled into ranges of prescribed dose likely to be tolerable when delivered in 2.5 and 4 week radiation and 6 week chemoirradiation schedules using conformal techniques. Worthwhile (w20%) gains in 30 month local progression-free survival should be achievable at safely deliverable levels of dose escalation. The analysis suggests that longer schedules may be more beneficial than shorter ones, but this finding is governed by the relative rates of tumour and oesophageal accelerated proliferation, which are quite imprecisely known. Consequently escalated 2.5, 4 and 6 week schedules are being developed; each should lead to useful improvements in local control but it is not yet known which schedule will be most effective. Fenwick, J. D. et al. (2009). Clinical Oncology jj, --ª
Translational Lung Cancer Research
Background: Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for most cases. While radiotherapy has historically served as a palliative modality in metastatic NSCLC, considerable advances in its technology and the continuous development of cutting-edge therapeutic agents, such as targeted therapy and immune checkpoint inhibitors (ICIs), are increasing its role in the multidisciplinary management of the disease. Methods: International radiotherapy experts were convened to consider and reach consensuses on the clinical utilities of radiotherapy in metastatic NSCLC, with the aim to provide patient-focused, up to date, evidence-based, recommendations to assist cancer specialists in the management of patients with metastatic NSCLC worldwide. Results: Timely radiotherapy can offer rapid symptom alleviation and allow subsequent aggressive treatment approaches in patients with heavy tumor burden and/or oncologic emergencies. In addition, appropriate incorporation of radiotherapy as concurrent, consolidation, or salvage therapy makes it possible to achieve long-term survival, or even cure, for patients with oligo-metastatic disease. Cranial radiotherapy plays an important role in the management of brain metastasis, potentially augmenting the response and prolonging survival associated with targeted agents and ICIs. However, key questions remain, such as the appropriate choice of radiation techniques, optimal sequence of systemic therapies and radiotherapy, and optimal patient selection for such combination strategies. Although a strong rationale for combining radiotherapy and ICIs exists, its optimal parameters in this setting remain to be established. Conclusions: In the modern era, radiotherapy serves not only as a palliative tool in metastatic NSCLC, but also plays active roles in patients with oligo-focal disease, CNS metastasis and receiving ICIs.
Open Journal of Social Sciences, 2020
International Journal of Sustainability in Higher Education, 2020
International Journal of English and Applied Linguistics (IJEAL), 2023
Color Research and Application, 2019
International Journal of Educational Research and Social Sciences, 2022
Quality and Quantity, 1976
Critical Reviews in Oncology/Hematology, 2009
E3S Web of Conferences, 2020
International Journal of Oncology, 2007
Advances in Animal and Veterinary Sciences, 2019
IEEE Transactions on Cognitive and Developmental Systems, 2018
Scientific Reports
Thermal Science, 2019
International journal of engineering research and technology, 2018