External beam radiation therapy alone for loco-regional recurrence of non-small-cell lung cancer after complete resection

doi:10.1016/S0169-5002(99)00007-0

Lung Cancer

Volume 23, Issue 2, February 1999, Pages 135-142

https://doi.org/10.1016/S0169-5002(99)00007-0 Get rights and content

Abstract

Between January 1982 and June 1993, a total of 61 patients with post-surgical loco-regional recurrence only were treated with external beam radiation therapy only at our institution. Patients were treated with either curative intent [tumor dose (TD) 55–60 Gy in 26–30 fractions] or palliative intent (TD 30 Gy in ten fractions). Median survival time (MST) for all 61 patients is 13 months, and 1–5-year survival rates are 61, 28, 16, 9.8 and 9.8%, respectively. There was a significant difference between high-dose and low-dose RT groups regarding both MST (18 vs. 7 months, respectively) and 1–5-year survival rates (74, 36, 24, 14 and 14% vs. 32, 11, 0, 0 and 0%, respectively) (P=0.0000). Age, extent of initial surgery, time from initial surgery to documented recurrence were not found to influence survival in the high-dose group and influence of performance status, weight loss and histology were only marginally insignificant. Females did better than males and patients with bronchial stump recurrence only did better than those with non-stump recurrence only. Initial and recurrent staging significantly influenced survival, with patients in early stages doing better than those in advanced stages. External beam RT is an effective tool in the treatment of loco-regional recurrent NSCLC after curative resection. Identification of a favorable subset of patients that may fare better may help optimize treatment in the future by using high-dose, curative RT. Otherwise, unfavorable patients may appropriately be treated with palliative RT.

Introduction

Surgery is the treatment of choice for early stages non-small-cell lung cancer (NSCLC), including sometimes patients with stage IIIA. Analysis of the patterns of failure shows that systemic failure occurring in completely resected patients renders them incurable [1]. On the other side, loco-regional recurrence is also well documented. As the first site of failure, it can range from as low as 3–9% (pathological stage I) to as high as 32% (pathological stage IIIA) or even 38%, depending on whether it was based on clinical or autopsy studies [2], [3], [4], [5], [6] or whether adjuvant treatment was administered [7], [8], [9], [10]. It is, therefore, not surprising that after curative resection 5-year survival ranges from as high as 54–83% for stage I squamous-cell carcinoma (SCC) to as low as 10–21% for stage IIIA adenocarcinoma [11], [12].

Although patients with loco-regional post-surgical recurrence are sometimes treated with more aggressive surgical approach [13], [14], [15], [16], there are reports [17], [18], [19] indicating the effectiveness of radiation therapy (RT) when given as a sole treatment modality. However, all these reports were evaluating small number of patients treated over prolonged periods of time and not in a homogeneous manner, often not specifying treatment outcome according to possible prognostic factors. Still, long-term survivals have been occasionally reported, especially in cases when recurrence was confined to bronchial stump [19], [20].

To investigate the effectiveness of RT alone in this patient population and to explore the influence of possible patient or treatment characteristics that may have influenced the outcome, we reviewed the data concerning post-surgical loco-regional recurrence only treated in a single institution over a period of 12 years.

Section snippets

Material and methods

Medical histories of all patients with NSCLC treated at the Department of Oncology, University Hospital, Kragujevac during the period 1982–1993 were reviewed. Eligible for this analysis were patients with loco-regional recurrence after attempted curative surgery and all patients had their resections histologically free of the disease. All patients had histologically or cytologically proven loco-regional recurrence defined as tumor confined to the ipsilateral hemithorax. In all cases the

Results

Between January 1982 and June 1993, a total of 61 patients with post-surgical loco-regional recurrence only were treated with exclusive external beam radiation therapy at our institution. Patients characteristics are given in Table 1. There was no difference among the various potential prognostic factors between the low-dose RT and high-dose RT groups of patients, except that patients treated with low-dose RT had significantly more frequent pre-RT weight loss>5% (P=0.033) and significantly more

Discussion

There are few reports on the use of external beam RT only in the treatment of postoperative loco-regional recurrence of NSCLC. Green and Kern [17] were first to report on such study with MST of 11 months and 2- and 4-year survival of 21% and 5%, respectively. Kopelson and Choi [18] reported on 24 patients to having MST of 12 months and 5-year survival of 10%. After RT, loco-regional failure was observed in 48% and distant metastasis in 57%.

Shaw et al. [22] reported on a series of 37 patients,

Acknowledgements

This study was supported in part by the Grant-in-Aid for Scientific Research (B) from the Japanese Ministry of Education, Science and Culture (09470200, 10557087).

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Citation Excerpt :
Of note, this favorable survival outcome is also attributed to the systemic chemotherapy, which is often added to SBRT of patients undergoing concurrent chemotherapy.54 For isolated bronchial stump recurrences, several studies documented high-dose radiation therapy as a viable option with excellent 5-year OS of 30% to 57%.55,56 The present meta-analysis revealed considerable morbimortality for CP.
Completion pneumonectomy (CP) for second primary/primary lung cancer (SPLC) and local recurrence lung cancer (LRLC) is still controversial. Although several case series on such a practice exist, the oncological benefit is under debate. The purpose of this study was to review available literatures on CP for SPLC and LRLC and evaluate postoperative and long-term outcomes.
MEDLINE, SCOPUS, and Web of Science were reviewed for eligible studies in January 2021. Studies were included if they indicated outcomes of patients with lung cancer undergoing CP. Overall survival (OS) was defined as the primary endpoint; secondary endpoints included operative morbidity and 30-day mortality. Random-effects meta-analysis based on a binomial distribution was used to create pooled estimates.
Thirty-two eligible studies including 1157 patients were identified. These studies were uniformly retrospective reports. Pooled estimates for 3-year and 5-year OS were 50.6% (95% confidence interval [CI], 34.7%-66.5%) and 38.9% (95% CI, 32.2%-46.1%) in SPLC patients. When the SPLC was a stage I tumor, pooled 5-year OS was favorable with 60.7% (95% CI, 43.2%-75.9%). In LRLC, pooled 3-year and 5-year OS were 47.6% (95% CI, 36.1%-59.4%) and 33.8% (95% CI, 26.8%-41.5%), respectively. Pooled morbidity and 30-day mortality was reported in 38.2% (95% CI, 32.0%-44.9%), and 10.0% (95% CI, 8.1%-12.3%), respectively.
CP for SPLC and LRLC is a challenging procedure with significant perioperative morbimortality. However, published evidence indicates good long-term survival for selected patients. Further studies are needed to identify patient subgroups which benefit most from CP.
Hypo-fractionated radiotherapy with concurrent chemotherapy for locoregional recurrence of non-small cell lung cancer after complete resection: A prospective, single-arm, phase II study (GASTO-1017)
2021, Lung Cancer
To explore the efficacy and toxicities of split-course hypo-fractionated radiotherapy with concurrent chemotherapy (HFRT−CHT) with intensity modulated radiotherapy (IMRT) technique in non-small cell lung cancer (NSCLC) patients with postoperative locoregional recurrence (LRR).
NSCLC patients were eligible if confirmed as LRR disease without distant metastasis after complete resection. HFRT−CHT using IMRT technique was administered with 51 Gy in 17 fractions or 40 Gy in 10 fractions as the first course followed by a break. Patients with no disease progression and no persistent Grade ≥2 toxicities had the second course of 15 Gy in 5 fractions or 28 Gy in 7 fractions as a boost. The primary endpoint was progression-free survival (PFS).
Fifty-eight patients were enrolled and analyzed. With a median follow-up of 23.9 months for all, the 2-year and 3-year PFS rate was 59.7 % and 46.4 %, the 2-year and 3-year OS rate was 72.5 % and 52.2 %, respectively, and a favorable objective response rate of 95.9 % was obtained after the whole courses protocol. Grade 3 acute pneumonitis and esophagitis occurred in 2 (3.4 %) and 7 (12.1 %) patients, and fatal pneumonitis was reported in one case (1.7 %). Exploratory subgroup analysis showed that performance status (PS) (PS 0 vs. 1: 2-year PFS, 88.1 % vs. 46.9 %,P = 0.001; 2-year OS, 100 % vs. 59.4 %, P < 0.001), recurrence site (single vs. multiple: 2-year PFS, 93.8 % vs. 47.4 %, P = 0.008; 2-year OS, 100 % vs. 63.0 %, P = 0.001), and gross tumor volume (GTV) (<50cm³ vs. ≥ 50cm³: 2-year PFS, 70.6 % vs. 46.2 %, P = 0.024; 2-year OS, 85.6 % vs. 57.4 %, P = 0.034) were significantly associated with PFS and OS.
Split-course HFRT−CHT with IMRT technique achieved promising disease control and satisfactory survival with moderate toxicities in postoperative LRR of NSCLC. Good PS, a single recurrence site and GTV<50cm³ tended to have prolonged PFS and OS. Early detection of LRR may improve the efficacy of HFRT−CHT.
Salvage Stereotactic Body Radiation Therapy for Isolated Local Recurrence After Primary Surgical Resection of Non–small-cell Lung Cancer
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We sought to evaluate the safety and efficacy of stereotactic body radiation therapy (SBRT) as salvage treatment for local recurrence after prior surgical resection for non–small-cell lung cancer (NSCLC).
We surveyed our prospective lung SBRT registry for patients who received salvage SBRT (sSBRT) for local recurrence after previous resection of a primary NSCLC. Following sSBRT, local control, distant metastases, overall survival, and treatment-related toxicity were evaluated.
From 2004 to 2017, 48 patients met inclusion criteria. At initial surgery, 44 (83%) patients had stage I to II disease, and surgical approaches were 47.9% wedge resection, 4.2% segmentectomy, 43.8% lobectomy, and 4.2% bilobectomy. The median time to local recurrence after surgery was 26.4 months, and 36 (75%) recurrences were biopsy-proven. Surgical salvage was not possible owing to un-resectability or underlying comorbidities in 45 (93.8%) patients. Most (68.8%) patients received 50 Gy in 5 fractions. The median follow-up after sSBRT was 22.6 months (range, 3.8-108.8 months). Eight (16.7%) patients experienced local or lobar failure, and 9 (19.1%) patients had nodal failure at a median of 12.5 months (range, 2-66.1 months). Nineteen (39.6%) patients failed distantly at a median of 11.4 months. The median overall survival after sSBRT was 29.3 months. A total of 72.9% of patients experienced no toxicity after sSBRT. Three (6.3%) patients developed grade III toxicity (cough, atelectasis, or soft tissue necrosis) following sSBRT.
Similar to SBRT for primary early stage NSCLC, sSBRT for local relapse following surgical resection of NSCLC offers high rates of local control with limited toxicity. Distant failure remains the primary pattern of failure.
Risk factors for local recurrence after lobectomy and lymph node dissection in patients with non-small cell lung cancer: Implications for adjuvant therapy
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Citation Excerpt :
These findings indicate that curative action is difficult once local recurrence occurs. Many studies showed that patients with postoperative local recurrence had poor prognoses even if they were treated with curative intent radiation therapy [21–23]. Meanwhile, local control improves OS, and adjuvant therapies with complete surgical resection are worth investigating to improve local control.
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We reviewed the records of 1012 consecutive stage I–III NSCLC patients who underwent complete resection. The median follow-up time was 59 months. The risk factors for local recurrence were investigated by multivariate analysis using Cox’s proportional hazards regression model.
Local recurrence was identified in 9.4% of the patients. The most significant risk factor for local recurrence was lymph node metastasis (N1: hazard ratio [HR] = 2.27, p = 0.009; N2: HR = 6.85, p < 0.0001). For the subgroup of patients with lymph node metastasis (n = 289), the independent risk factors for local recurrence were N2 disease with N1 metastasis (N2 with N1; HR = 3.46, p < 0.0001) and non-receipt of adjuvant platinum-based chemotherapy (HR = 1.91, p = 0.018). The 5-year freedom from local recurrence rates were 96.1%, 84.1%, 85.0%, and 53.5% for N0, N1, skip N2, and N2 with N1 stages (p < 0.0001).
Local recurrence is significantly associated with poor overall survival. Therefore, local control is essential for radical cure of NSCLC. N2 with N1 status was the primary risk factor for local recurrence, while adjuvant chemotherapy improved local control. These data have important implications for postoperative radiotherapy and highlight the need to devise more effective eligibility criteria for this modality in patients with lymph node metastasis.
Comparison of Radiotherapy and Chemoradiotherapy for Locoregional Recurrence of Non–small-cell Lung Cancer Developing After Surgery
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The optimal treatment strategy for locoregional recurrences developing after surgical resection in patients with non–small-cell lung cancer (NSCLC) is yet to be clearly established.
To investigate the efficacy and safety of radiotherapy (RT) and chemoradiotherapy (CRT), we reviewed the consecutive data of patients with NSCLC with postoperative locoregional recurrences treated at the National Cancer Center Hospital between January 2000 and April 2010.
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CRT tended to yield better results than RT in terms of the survival outcomes, with acceptable safety profiles of both. We consider that a randomized study comparing RT and CRT is warranted to identify the optimal treatment strategy for patients with NSCLC with postoperative locoregional recurrences.
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External beam radiation therapy alone for loco-regional recurrence of non-small-cell lung cancer after complete resection

Abstract

Introduction

Section snippets

Material and methods

Results

Discussion

Acknowledgements

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Ann Thorac Surg

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Chest

Mayo Clin Proc

Lung Cancer

Lung Cancer

Int J Radiat Oncol Biol Phys

J Thorac Cardiovasc Surg

Chest

Int J Radiat Oncol Biol Phys

Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer-report of a Canadian multicenter randomized trial

J Clin Oncol