Positron emission tomography imaging in lung cancer

Over the past several years, positron emission tomography (PET) has become a clinically useful, noninvasive study which complements conventional imaging (chest radiographs, computed tomography [CT], and magnetic resonance imaging [MRI]) in the evaluation of patients with lung cancer. PET imaging of lung cancer is typically performed with the radiopharmaceutical 18F-2-deoxy-D-glucose (FDG), a d-glucose analog. Increased glucose metabolism by malignant cells results in increased uptake and accumulation of FDG, which serves as the basis for tumor detection. This review will focus on the current applications of FDG-PET in lung cancer patients including evaluation of focal pulmonary abnormalities, staging lung cancer, determining tumor recurrence, and in assessing prognosis.     

Positron emission tomography in nonsmall cell lung cancer

PURPOSE OF REVIEW: Positron emission tomography (PET) has become a major adjunct to structural imaging for nonsmall cell lung cancer. Established indications are the differential diagnosis of lung nodules, as well as mediastinal lymph node and extrathoracic staging. RECENT FINDINGS: More details for small or faint pulmonary nodules became available--information of interest in the era of lung cancer screening trials, in which PET might help to reduce unwanted invasive procedures for benign findings. The strength of PET in mediastinal staging (its high negative predictive value) was confirmed in a randomized study, in which PET reduced the number of invasive procedures without loss of accuracy in staging. Isolated positive lesions that are decisive for radical compared with palliative treatment should be confirmed by other tests, as they may be benign or due to second primary cancer. PET with integrated computed tomography (CT) may guide modern radiotherapy, by improving radiation fields. Integrated PET-CT is a promising tool in the indication for surgery in stage IIIA-N2 patients after induction treatment. Predictive values for lymph node downstaging become in acceptable ranges and PET response in the primary tumor could be clearly linked to pathologic response and survival. SUMMARY: In recent years, PET has seen further refinements in established indications and definition of new indications.     

Positron emission tomography imaging in nonsmall-cell lung cancer

Positron emission tomography (PET) using 18F-2-deoxy-D-glucose, a D-glucose analog labeled with fluorine-18, complements conventional radiologic assessment in the evaluation of patients with nonsmall-cell lung cancer (NSCLC). PET is being routinely used to improve the detection of nodal and extrathoracic metastases. PET is also currently being evaluated in the assessment of prognosis and therapeutic response and by potentially allowing an earlier assessment of response may prove invaluable in the oncologic management of patients. The article discusses the diagnosis, staging, and assessment of treatment response and prognosis with an emphasis on the appropriate clinical use of PET in management.     

Radiation dose escalation in limited-stage small-cell lung cancer

PURPOSE: To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients treated with > or =50 Gy of radiation at Massachusetts General Hospital (MGH) between 1987 and 2000 and to assess for evidence of a continuation of a radiation dose response. METHODS AND MATERIALS: The MGH cancer registry was searched for SCLC patients treated with radiotherapy between 1987 and 2000. Records of LS-SCLC patients treated with curative intent and radiation doses > or =50 Gy at MGH were reviewed. Surgical patients were excluded. RESULTS: Eighty-four LS-SCLC patients were treated with radiotherapy at MGH between 1987 and 2000. Of the 84 patients, 54 (64%) met the inclusion criteria; 30 patients (56%) in this study died, and 4 (7%) were lost to follow-up. The median follow-up of the surviving patients was 42 months. The median overall survival was 29 months. The 2- and 5-year survival rate was 64% and 47%, respectively. The local control rate at 3 years was 78%. CONCLUSION: The overall survival, local control, and disease-free survival rates for LS-SCLC patients treated with > or =50 Gy of radiation compare favorably with historical data. These findings suggest a continuation of the radiation dose-response curve in LS-SCLC. This further supports the need for appropriately powered, Phase III, prospective randomized trials in radiation dose escalation or radiation dose intensification for LS-SCLC.     

Radiation dose intensification in limited-stage small-cell lung cancer

Multiple studies have confirmed the value of radiation therapy in limited-stage small-cell lung cancer. The appropriate dose of radiation and the optimal fractionation scheme, however, remain controversial. This article will examine the history of radiation therapy in the management of small-cell lung cancer. It will review the rationale for the various approaches to radiation dose intensification, and review the results of important trials investigating the issue of radiation dose in the management of this disease. Survival outcomes and toxicity of various approaches to radiation dose intensification, including dose escalation and hyperfractionation, will be assessed. The implications of advancements in technology will be examined, and the optimal design of future trials will be discussed.     

Dose escalation model for limited-stage small-cell lung cancer

Background and purpose

To construct a model for the local dose-response relationship of limited-stage small-cell lung cancer (LS-SCLC) along with subsequent models for dose-per-fraction escalation.

Materials and methods

Reported doses and 2-year progression free survival (PFS_2year) rates from LS-SCLC studies were used to construct a dose-response model. Modeling incorporated effects of chemotherapy, incomplete repair of sublethal damage and variations in both kick-off time for rapid reproliferation and effective tumor cell doubling time. Response was modeled as a function of overall treatment duration in order to shed light on the optimum radiotherapy treatment duration. Subsequent models were constructed for more aggressive radiotherapy by means of dose-per-fraction escalation for once a day (QD) and twice a day (BID) fractionation schedules.

Results

Modeling response as a function of treatment duration resulted in an optimum treatment duration of 3 weeks for both fractionation schedules. Modeling for dose-per-fraction escalation resulted in an increase in the expected local PFS_2year for both fractionation schedules with possible gains in a BID schedule with lower expected late complication rates than a QD schedule yielding the same expected local PFS_2year.

Conclusions

This modeling suggests more aggressive treatment through escalation of dose-per-fraction, which may result in substantial gains in local PFS_2year. This points towards treatment durations of 3 weeks as being optimal with a BID schedule predicting possible gains in local PFS_2year at lower rates of expected late complications than a QD schedule.     

局限期小细胞肺癌全脑预防照射保护海马回区的初步临床研究

目的 初步观察局限期SCLC化放疗后HT的PCI对海马回区保护照射后的临床反应,并与IMRT、VMAT计划剂量分布进行比较。方法 2014年4－6月,6例局限期SCLC化放疗后达CR患者1个月内脑核磁排除脑转移后接受保护海马回区HT的PCI。将CT定位图像与脑核磁图像进行融合,在融合图像上勾画出海马回,外扩3 mm边界形成减量区域。HT、IMRT、VMAT处方剂量均为95%PTV 25 Gy分10次。评价HT的临床疗效、不良反应、认知功能及脑转移情况,比较3种计划靶区、海马回区剂量分布。结果 观察期内1例腹壁及腹腔淋巴结转移、1例局部复发,无脑转移。1+2级头痛、头晕、脱发反应分别为3+1、3+1、4+2例,复诊MMSE平均得分与疗前相近(29.2、29.3、29.7分,P=0.083、0.317、0.157)。IMRT、VMAT计划的海马回区D_mean分别为16.85、17.59 Gy。HT计划可将海马回区D_mean降至5.26 Gy、外扩减量区降至6.21 Gy,处方剂量分别比IMRT、VMAT的降低79%、71%。HT平均处方剂量覆盖率为94.48%。结论 应用HT保护海马回区PCI达到了理想剂量分布及较好靶区覆盖度,患者不良反应未增加,认知功能变化尚需延长观察时间及扩大病例进一步研究。     

Thoracic radiation therapy for limited-stage small-cell lung cancer: unanswered questions

The role of thoracic radiation therapy (RT; TRT) is now established in the management of limited-stage small-cell lung cancer (SCLC). There is increasing evidence in the literature in favor of early concurrent chemoradiation therapy, and a gold standard of care for patients with a good performance status is twice-daily TRT (45 Gy in 3 weeks) with concurrent cisplatin/etoposide. Five-year survival rates > 20% can be expected with this combined-modality approach. Although current clinical trials are exploring the efficacy of new chemotherapeutic strategies for the disease, essential questions related to the optimization of TRT remain unanswered. In particular, the optimal RT dose, fractionation, and treatment volume have not been defined. This review highlights the need for well-designed multinational trials aimed at the optimization and standardization of RT for limited-stage SCLC. These trials should integrate translational research studies to investigate the molecular basis of RT resistance and to develop biomarker profiles of prognosis.     

Phase I study of hypofractionated dose-escalated thoracic radiotherapy for limited-stage small-cell lung cancer

PURPOSE: To determine the maximal tolerated dose of hypofractionated thoracic radiotherapy with concurrent chemotherapy for limited-stage small-cell lung cancer patients. METHODS AND MATERIALS: Three radiotherapy regimens were used. Radiotherapy was given in two phases: patients initially received 20 Gy in 10 fractions to gross tumor plus uninvolved mediastinal nodes, followed by a boost to gross disease of 30, 38, or 42 Gy in 15 fractions. Radiotherapy was planned with conformal techniques. All patients received four cycles of cisplatin (25 mg/m2) and etoposide (100 mg/m2) chemotherapy. Radiotherapy commenced with Day 1 of Cycle 2 of chemotherapy. All complete/near-complete responders were offered prophylactic cranial irradiation. The maximal tolerated dose of radiotherapy was based on the dose that caused unacceptably high rates of radiotherapy-related toxicity. RESULTS: Thirteen patients were accrued. All patients who commenced radiotherapy received all prescribed chemo- and radiotherapy. There were no treatment-related deaths. There was one Grade 3 acute nonhematologic toxicity in the 50-Gy group. Of the 6 patients given 58 Gy, 3 experienced acute Grade 3 esophagitis. With a median follow-up of 7 months, median overall survival was 9.5 months. CONCLUSIONS: The maximal tolerated dose of thoracic radiotherapy with concurrent chemotherapy on this trial was 50 Gy in 25 daily fractions.     

Positron emission tomography in the management of non-small cell lung cancer

In the past 10 years, FDG-PET has become an important imaging modality in NSCLC. Its indication in the assessment of lung nodules and staging is based on large prospective experience, further supported by some meta-analyses. This evidence has important consequences for patient management, which recently was proved in a randomized trial that showed a reduction in the number of futile thoracotomies by preoperative PET. The use of FDG-PET could become more widespread when commercial isotope distributors are able to deliver FDG so that an on-site cyclotron is no longer a prerequisite. FDG has a half-life of 110 minutes, so a practical distribution radius of 200 km should be feasible. Current indications for PET in the staging of newly diagnosed NSCLC are mainly the patients who are considered to be candidates for radical treatment. The technique does not have a clinical indication in other patients--for example, when metastatic lymph nodes are detected at clinical examination, when a simple ultrasound study already points to diffuse hepatic metastases, or in cases of poor performance status. PET also has prognostic value; it can be used for the evaluation of response or restaging after radiotherapy or chemotherapy and for early detection of relapse. The combination of CT and PET improves radiotherapy planning and it is to be expected that combined CT-PET-guided planning devices will further refine three-dimensional conformal radiotherapy. Finally, a whole new field of application of PET in molecular biology using new radiopharmaceutics is in development. FDG, with its possibility to study tumor glucose metabolism, has paved the way for PET in clinical oncology. It is hoped that PET examinations with new molecular tracers will allow ever better specificity and become sufficiently reliable and manageable to evaluate receptors, transport proteins, and intracellular enzymes so that very early response monitoring during chemotherapy or radiotherapy, evaluation of novel molecular-targeted lung cancer therapies, or even gene therapy becomes possible. New tracers that have showed their promise in early clinical studies include 18F-fluorothymidine (a proliferation marker that might give better specificity in the assessment of solitary pulmonary nodules or better accuracy in the evaluation of early response), (99m)Tc-Annexin V (Apomate; an apoptosis-imaging agent that could be correlated with overall and progression-free survival in phase I data), or 18F-fluoromisonidazole (which can be used to quantify regional hypoxia in human tumors with PET).     

Positron emission tomography to assess hypoxia and perfusion in lung cancer

In lung cancer, tumor hypoxia is a characteristic feature, which is associated with a poor prognosis and resistance to both radiation therapy and chemotherapy. As the development of tumor hypoxia is associated with decreased perfusion, perfusion measurements provide more insight into the relation between hypoxia and perfusion in malignant tumors. Positron emission tomography (PET) is a highly sensitive nuclear imaging technique that is suited for non-invasive in vivo monitoring of dynamic processes including hypoxia and its associated parameter perfusion. The PET technique enables quantitative assessment of hypoxia and perfusion in tumors. To this end, consecutive PET scans can be performed in one scan session. Using different hypoxia tracers, PET imaging may provide insight into the prognostic significance of hypoxia and perfusion in lung cancer. In addition, PET studies may play an important role in various stages of personalized medicine, as these may help to select patients for specific treatments including radiation therapy, hypoxia modifying therapies, and antiangiogenic strategies. In addition, specific PET tracers can be applied for monitoring therapy. The present review provides an overview of the clinical applications of PET to measure hypoxia and perfusion in lung cancer. Available PET tracers and their characteristics as well as the applications of combined hypoxia and perfusion PET imaging are discussed.     

Mid-course thoracic radiotherapy with cisplatin-etoposide chemotherapy in limited-stage small-cell lung cancer

Combination chemoradiotherapy is a standard treatment for limited-stage small-cell lung cancer (LS-SCLC). However, there is still controversery about the optimal timing of thoracic radiotherapy (TRT). In this study, the outcome of 70 patients who had received TRT at a dose of median 50 Gy (range, 46–60 Gy) with a second or third cycle of chemotherapy (CHT) either concurrently (n=41) or sequentially (n=29) were analyzed retrospectively. All patients were administered a median of five cycles (range, four to six cycles) cisplatin plus etoposide (EP) CHT. Prophylactic cranial radiotherapy was delivered to 30 (43%) patients. The median follow-up for all patients was 15 mo (range, 6–60 mo). The median overall survival was 19 mo in the concurrent arm vs 15 mo in the sequential arm. The 2-yr local control, disease-free survival, and overall survival rates were 60%, 19%, and 36%, respectively. The most common toxicity was esophagitis. However, there were no grade 3–4 esophagitis in either arm. Grade 3–4 hematologic toxicity, on the other hand, appeared significantly more in the concurrent arm (p<0.001). Mid-course of once-daily TRT at a moderate total dose with CHT failed to show any improvement in survival. Additionally, there were no differences between concurrent and sequential CHT with TRT. However, acceptable toxicity rates support the use of once-daily fractionation to higher total dose of TRT.     

Positron emission tomography imaging of colorectal cancer.

Continued improvements in the diagnosis and treatment of colorectal cancer are based on a clearer understanding of the pathophysiological processes underlying the disease and how it affects the patient. The addition of information derived from fluorine-18-labeled deoxyglucose (FDG) positron emission tomography (PET) scans to the cross-sectional imaging data enables a clearer understanding of the pathophysiology of the disease process. In particular, FDG PET scans are capable of demonstrating disease that mimics normal structures on conventional imaging, as well as finding disease in otherwise normal-sized lymph nodes. Abnormal areas of FDG uptake in the setting of known colorectal cancer are almost always due to recurrent disease. In addition, FDG PET offers great promise in the evaluation of treatment response, particularly as more targeted therapies become available. This report covers the basic principles underlying PET imaging, including the biochemistry of FDG and methods of PET analysis. We then, review the clinical indications for FDG PET scanning in colorectal cancer.     

Thoracic radiotherapy for limited-stage small-cell lung cancer: controversies and future developments

Thoracic radiotherapy has an established role in the management of limited-disease small-cell lung cancer (LD SCLC). However, essential questions relating to the optimisation of thoracic radiotherapy remain unanswered, including volume of irradiation, optimal total dose, fractionation, timing and sequencing of radiation. This review highlights the need for well-designed multi-national trials aimed at the optimisation and standardisation of radiotherapy for LD SCLC.