Heavy-ion therapy for non-small cell lung cancer

Since carbon beam therapy for non-small cell lung cancer (NSCLC) was initiated in October 1996, seven trials have been conducted; three have already closed and the remaining four are ongoing. The local control rate, cause-specific survival rate, and overall survival rate of 141 patients with clinical stage I NSCLC were 82%, 58%, and 42%, respectively. Radiation pneumonia was rare (2.1%) and not serious. In the phase II clinical study, the local control rate achieved in 50 patients was 100%, with no radiation pneumonia, resulting in a 60% overall survival rate. Carbon beam therapy could be an alternative to surgery, especially for lung cancer patients of advanced age and/or with complications. For locally advanced lung cancer treated with carbon beam therapy, excellent local control comparable to that in stage INSCLC has been demonstrated and offers hopeful prospects for the treatment of lung cancer.     

Heavy ion therapy for non-small cell lung cancer

Carbon beam radiation has well-balanced dual actions on cancer: efficient dose localization and potent biological anticancer effect due to high RBE (Relative Biological Effectiveness). Two phase I/II clinical studies on the carbon beam radiation treatment of inoperable stage I non-small cell lung cancer (NSCLC) were carried out in our institution from October 1996 to February 1999. The dose-limiting toxicity was found to be radiation pneumonia. In the first protocol, 47 patients received 18 fractions of increasing doses from 59.4 GyE by 10% over 6 weeks. The maximum tolerated dose was found to be 95.4 GyE, while the complete tumor control dose was 85.6 GyE. In the second protocol, 34 patients received 9 fractions of in creasing doses from 68.4 GyE by 5% over 3 weeks. The maximum tolerated dose was 79.2 GyE, and the complete tumor control dose was > 68.9 GyE. The 4-year survival rate estimated by the Kaplan-Meier method was 56% for patients receiving the first protocol. Because a higher local control rate was achieved in the second protocol, the 5-year survival rate is estimated to be higher and similar to that achieved after surgery. Another phase II clinical study in patients with stage INSCLC is ongoing. Heavy-particle radiotherapy is a new modality for the treatment of lung cancer which holds promise for the 21st century.     

非小细胞肺癌EGFR罕见突变及其靶向与免疫治疗策略

表皮生长因子受体(EGFR)基因的激活突变包括经典突变和罕见突变。罕见突变病人数量少,不同突变类型对不同的EGFR酪氨酸激酶抑制剂的敏感性差异较大。本文将对各种罕见突变进行系统回顾,总结针对罕见突变的临床前研究和临床研究,为临床治疗决策提供依据。     

"Personalizing" therapy for non-small cell lung cancer

The sequencing of the human genome has lead to an even greater understanding of the genetic basis of numerous diseases. During the past several years, genetic approaches to a number of solid organ malignancies, including non-small cell lung cancer, have lead us to an increased understanding of the disrupted genetic pathways involved in tumor initiation and progression. Two recent articles are reviewed that highlight the broad potential for successful targeted therapy in thoracic malignancies.     

Preoperative induction therapy in non-small cell lung cancer

The clinical significance of preoperative induction therapy for non-small cell lung cancer (NSCLC) is reviewed. As the survival rate in locally advanced NSCLC patients remains poor, preoperative therapy has been attempted in order to improve survival. Whereas some prospective phase II and phase III studies have demonstrated that preoperative cisplatin-based chemotherapy with or without concurrent radiation may improve the prognosis, the efficacy has not been established. Recently, some new chemotherapeutic agents such as paclitaxel and gemcitabine have been introduced, and it has been suggested that preoperative therapy using these new drugs may be more effective. To establish effective preoperative therapy regimens, more sophisticated, prospective, randomized studies in sufficient numbers of homogenous populations such as mediastinoscopy-proven stage IIIA, T1-2N2 patients should be conducted.     

Induction concurrent chemoradiation therapy for invading apical non-small cell lung cancer

Objective: Although non-small cell lung cancer (NSCLC) involving the superior sulcus has been generally treated with radiation therapy (RT) followed by surgery, local recurrence is still a big problem to be solved. We investigated a role of induction therapy, especially induction concurrent chemoradiation therapy (CRT), on the surgical results of this type of NSCLC. Method: We retrospectively reviewed 30 patients with NSCLC invading the apex of the chest wall who underwent surgery from 1987 to 1996. Ten patients (57±8 years) received surgery alone, 9 (55±13 years) received RT (42±7 Gy) followed by surgery and 11 (51±9 years) received cisplatin based chemotherapy and RT (47±5 Gy) as an induction therapy. Results: Two and 4-year survival rates were 30% and 20% in patients with surgery alone, 22% and 11% in patients with induction RT, and 73% and 53% in patients with induction CRT, respectively. The survival was significantly better in patients with induction CRT than those with induction RT or surgery alone. Univariate analysis demonstrated that curability (yes versus no: p=0.027) and induction therapy (surgery alone and RT versus CRT: p=0.0173) were significant prognostic factors. Multivariate analysis revealed that only induction therapy (p=0.0238) was a significant prognostic factor. Conclusions: Induction CRT seems to improve the survival in patients with NSCLC invading the apex of the chest wall compared with induction RT or surgery alone.     

Stereotactic body radiation therapy for stage I non-small cell lung cancer

Image-guided SBRT with the delivery of a BED greater than 100 Gy is feasible and safe in the treatment of peripherally located inoperable stage I NSCLC. The 3- to 5-year local control and overall survival rates for SBRT seem to be much better than the rates for conventional radiotherapy, and the toxicity rate is minimal. Particularly for stage Ia (T1N0M0) disease, survival rates with SBRT were comparable with rates seen with surgical resection. SBRT is becoming the standard treatment for inoperable stage I NSCLC. Its role in operable stage I NSCLC. however. is not clear. To balance improved targeting accuracy with minimized treatment-related toxicity. a reliable immobilization device and consideration of image-guided tumor motion are crucial. The optimal dose regimen remains unclear, but a BED greater than 100 Gy seems warranted.     

Neoadjuvant therapy of stage III non-small cell lung cancer

During the past several years, there has been a resurgence of interest in preoperative or postoperative chemotherapy in patients with Stage III lung cancer. The staging system for lung cancer has recently been modified, and at the present time Stage III disease is now subdivided into Stage III-A (potentially surgically resectable for cure) and Stage III-B (unresectable). This article will review five recently completed studies utilizing neoadjuvant therapy in various types of Stage III lung cancer. The thoracic surgeon is faced with the dilemma of reviewing this literature and trying to make a conclusion as to what is appropriate therapy for Stage III disease. Unquestionably, neoadjuvant therapy appears to increase the resectability rate in Stage III-A disease and can make some Stage III-B patients anatomically resectable. It is hoped that future well-designed phase III studies can be accomplished in Stages III-A and III-B disease so that we can determine whether neoadjuvant chemotherapy is or is not beneficial for these patients.     

Pneumonectomy for non-small cell lung cancer

Purpose

To assess the mortality, complications and major morbidity of pneumonectomy for non-small cell lung cancer (NSCLC) and to establish the importance of various prognostic factors.

Methods

We reviewed retrospectively the hospital records of 71 consecutive patients who underwent pneumonectomy for NSCLC between 1992 and 2007 to evaluate the significance of risk factors for an adverse outcome. Patients were divided into two period groups according to the period when they were treated: early (1992–1999; n?=?47) and late (2000–2007; n?=?24).

Results

Both the 30-day and the in-hospital mortality rates were 4.2?% (3/71). Complications developed in 31.3?% (22/71) and overall 5-year survival was 23.1?%. Pathological stage III or more, T3 or more, and N2 or more were risk factors of an adverse outcome. Survival was not significantly influenced by histological type, the side of surgery, or curability. The 5-year survival rates for the early and late periods were 19.6 and 32.9?%, respectively. There were more patients with clinical N2 or 3 disease in the early period than in the late period (66.0 vs. 33.3?%).

Conclusions

Pneumonectomy is associated with acceptable overall morbidity and mortality; however, patients with pathological stage III or more, T3 or more, and N2 or more disease require special consideration. Pneumonectomy should be performed only in selected patients.     

Surgical strategies and outcomes after induction therapy for non-small cell lung cancer

Surgery as the sole therapy for locally advanced non-small cell lung cancer (NSCLC) is usually not curative. Adjuvant chemotherapy has been evaluated by several randomized Phase III trials and found to confer a survival benefit over surgery alone for stage IB-IIIA NSCLC. Induction therapy applies a cytoreductive and systemic therapy before definitive locoregional therapy. Theoretical advantages include improved diffusion of chemotherapy agents into the tumor, improved compliance, and a higher complete resection rate. Results from multiple Phase II and III studies have been encouraging, but the role of surgery after induction therapy remains inconclusively defined. Randomized trials are underway to better define the role of induction therapy, and enrollment of patients into such trials should be encouraged.     

Molecular staging and the selection of therapy for non-small cell lung cancer

The stage-specific selection of therapy is the standard for patients with non-small cell lung cancer. Investigation of the molecular biology of lung cancer has provided pathways and targets that may be used to improve the efficacy of therapy and improve the survival for patients with lung cancer.     

Adjuvant chemotherapy for non-small cell lung cancer

The survival after complete resection for non-small cell lung cancer (NSCLC) is unsatisfactory. Until recently, the use of adjuvant therapy after resection for early stage disease has not been proven to improve survival. However, the efficacy of adjuvant therapy has been demonstrated in phase III prospective randomized trials. The appropriate use of adjuvant therapy, including biologic therapy, is currently under investigation.     

Sleeve lobectomy for non-small cell lung cancer

Sleeve lobectomy is a procedure in which the involved lobe with part of the main stembronchus is removed. The remaining lobe (s) is reimplanted on the main stembronchus. This procedure is indicated for central tumors of the lung as an alternative to pneumonectomy. It is the aim of this study to describe the technique of sleeve lobectomy and to analyse the early postoperative results and late results (survival-recurrence) after sleeve lobectomy for non-small-cell lung cancer. MATERIAL AND METHODS: Between 1985 and 1999, 77 sleeve lobectomies for bronchogenic carcinoma were performed at the University hospitals Leuven. The most common performed sleeve lobectomy is the right upper lobe sleeve lobectomy (67.5%). In 6 patients a combined sleeve resection of the pulmonary artery was performed. The operative mortality was 3.9%. Two patients developed a broncho-pleural fistula. The five-year survival rate was 45.6%. In 5 patients, an anastomotic suture developed which required a completion pneumonectomy in 2. Thirteen patients developed local tumor recurrence. CONCLUSION: We conclude that sleeve lobectomy can be performed with an acceptable mortality and morbidity. Long term survival rate and recurrence rate are as good as after pneumonectomy. The operative mortality is lower when compared to pneumonectomy, exercise tolerance and quality of life are much better after sleeve lobectomy compared to pneumonectomy. For central tumours we believe that sleeve resection is the procedure of choice.     

Neoadjuvant therapy of stage III non-small cell lung cancer]

Locally advanced stage III disease constitutes 30 to 40% of the entire group of non-small cell lung cancer. Surgery is the only curable modality in this stage disease, but resection rate is less than 40%. Even in completely resected patients 5-year survival is only 30%. Several reports have evaluated postoperative chemotherapy and radiotherapy. Prospective randomized studies, however, have failed to demonstrate a survival advantage from adjuvant therapy. Neoadjuvant therapy is under investigation in attempt to improve survival of stage III patients. Preliminary data show that neoadjuvant therapy could increase resection rate and improve survival with moderate toxicities. However, there are many problems in study design such as the use of single-arm studies with short duration of follow-up, lack of accurate staging of selected patients and no precise definitions of resectability for stage III disease. Therefore, there is an urgent need for well designed randomized trial to confirm whether neoadjuvant therapy offers a survival advantage on locally advanced stage III disease.     

The effect of multimodality induction therapy for locally advanced non-small cell lung cancer

In this study we analyzed induction therapy for locally advanced non-small cell lung cancer. Eligible patients had mediastinoscopic proven N2 disease and T4 with mediastinal involvement. From January 1997 to May 2005, 56 patients entered the study. They received 2 cycle chemotherapy (platinums based 2 or 3 drugs), in 32 patients with concurrent radiotherapy followed by surgery. Response rates were 57.1%. Fifty-one patients underwent surgery. A radical resection was possible in 39 patients. Complication occurred in 14 patients (27.5%). Overall 5-year survival was 27.5%. In N2 disease, there was no statistically significant difference in survival between the induction group and the historical group. In T4 disease, overall 5-year survival was 30.2% for the induction group and 5.2% for historical group. There was significant difference in survival between the groups (p < 0.05).     

Locally advanced non-small cell lung cancer completely resected after induction therapy

We analyzed 8 patients with unresectable locally advanced non-small cell lung cancer who responded to chemotherapy or chemoradiotherapy and underwent complete resection between June 2003 and June 2005. The patients were all male with a mean age of 61 years (range, 42 to 72 years). Histological subtypes included adenocarcinoma in 4 patients and squamous cell carcinoma in 4 patients. Clinical staging included T2N2M0 in 3 patients, T2N3M0 in 2 patients, and 1 patient each for T3N2M0, T4N2M0, and T4N3M0. Preoperative treatment included chemotherapy in 5 patients and chemoradiotherapy in 3 patients, all of whom had a partial response. Surgical procedures included lobectomy in 6 patients and pneumonectomy in 2 patients. In addition, all of the patients underwent mediastinal lymph node dissection (ND2a). Pathological effect included Ef. 0 in 1 patient, Ef. 1 in 2 patients, Ef. 2 in 2 patients, Ef. 3 in 3 patients. The median survival time from initial treatment (or surgery) was 16 (14) months in all cases, 22 (19) for ycN0, 12 (8) for ycN2, 31 (27) for Ef. 3, 13 (9) for Ef. 0-2, 27 (23) for pN0, 13 (9) for pN1-3, 31 (27) for chemoradiotherapy, 16 (13) for chemotherapy, 24 (21) for adenocarcinoma, and 15 (11) for squamous cell carcinoma. Multimodality treatment, including surgery, is beneficial for patients with unresectable locally advanced non-small cell lung cancer who respond to chemotherapy or chemoradiotherapy, especially those patients with ycN0 or pN0.     

Resection of stage III non-small cell lung cancer following induction therapy

Approximately 25%–30% of all patients with non-small cell lung cancer (NSCLC) present with stage III tumors. Except for specific subsets, these tumors are not usually amenable to complete surgical resection and are associated with a 5-year survival of 10% or less. Because patients with stage III NSCLC die of distant metastases, recent efforts to improve the prognosis of these tumors have focused on neoadjuvant therapy using chemotherapy or chemoradiotherapy as induction treatment and subsequent surgical resection for local control. Many trials have now shown the feasibility of neoadjuvant therapy and suggest that overall survival is approximately double that seen after surgical resection or radiation alone. Future clinical trials will define whether surgical resection after induction therapy provides better local control and survival than chemotherapy and high-dose radiation alone.

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Resumen Aproximadamente 25–30% de la totalidad de los pacientes con cáncer pulmonar de células no pequeñas se presentan con tumores en estado III. A excepción de algunos subgrupos específicos, tales tumores usualmente no son susceptibles de resección quirúrgica completa y se asocian con una tasa de sobrevida de 5 años de 10% o menos. Debido a que los pacientes en estado III mueren por metástasis distantes, los esfuerzos recientes encaminados a mejorar el pronóstico se han concentrado en la terapia neoadyuvante utilizando quimioterapia o quimioradioterapia como tratamiento de inducción y resección quirúrgica subsiguiente para el control local de la enfermedad. Muchos ensayos clínicos han demostrado la factibilidad de la terapia neoadyuvante y sugieren que la tasa global de sobrevida es aproximadamente el doble de la que se ve en pacientes sometidos a resección quirúrgica o a irradiación solamente. Los futuros ensayos clínicos deben definir si la resección quirúrgica luego de la terapia de inducción resulta en mejor control local y mejor sobrevida que con la quimioterapia o la irradiación solamente.

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Résumé Environ 25–30% de tous les patients ayant un cancer autre qu'à petites cellules du poumon (non-small cell lung cancer ou «NSCLC») se présentent au stade III de leur maladie. Exceptés des sous-groupes spécifiques, ces tumeurs ne sont généralement pas traitables par la résection chirurgical complète et leur survie à 5 ans est de 10% ou moins. Parce que les patients des stades III des NSCLC meurent habituellement des métastases à distance, des efforts récents pour améliorer le pronostic se sont centrés sur la chimiothérapie néoadjuvante, c'est-à-dire par la chimiothérapie ou la chimioradiothérapie en induction suivie de résection locale. Beaucoup d'essais ont démontré la faisabilité de la thérapie néoadjuvante, et suggèrent que la survie globale est environ la double de celle après résection chirurgicale ou radiothérapie seule. Des essais cliniques futurs sont seuls capables de démontrer si la résection après l'induction thérapeutique par la chimiothérapie adjuvante peut contrôler la maladie et améliorer le pronostic par rapport à la chimiothérapie et la radiothérapie seules.