Japanese Journal of Clinical Oncology Advance Access originally published online on June 16, 2006
Japanese Journal of Clinical Oncology 2006 36(7):457-461; doi:10.1093/jjco/hyl044
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© 2006 Foundation for Promotion of Cancer Research
Case Report |
Relapse of Stage I Small Cell Lung Cancer Ten or More Years after the Start of Treatment
1 Department of Thoracic Malignancy, 3 Department of Thoracic Surgery, and 5 Department of Pathology, Medical Center for Respiratory and Allergic Diseases of Osaka Prefecture, Osaka, Japan, 2 Division of Respiratory Medicine, Gifu Municipal Hospital, Gifu, Japan, 4 Department of Radiology, Osaka City Medical School, Osaka, Japan and 6 Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan
For reprints and all correspondence: Kaoru Matsui, Department of Thoracic Malignancy, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, 3-7-1 Habikino, Habikino-City, Osaka 583-8588, Japan. E-mail: kmatsui{at}hbk.pref.osaka.jp
Received January 20, 2006; accepted April 7, 2006
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Abstract |
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 TOP Abstract INTRODUCTIONCASE REPORTSDISCUSSIONReferences |
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Most patients with small cell lung cancer (SCLC) usually show relapse within 1 or 2 years. Relapses after a 5-year disease-free survival are extremely rare. This report describes two patients with stage I SCLC in whom the disease recurred 10 or more years after the start of initial therapy. Because the recurrence of SCLC was noted in the mediastinal lymph nodes of the same side, we concluded that the patients had a late relapse of SCLC rather than a metachronous lung cancer.
Key Words: 10-year disease-free survival • late relapse • second malignancy • small cell lung cancer
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INTRODUCTION |
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TOPAbstractINTRODUCTIONCASE REPORTSDISCUSSIONReferences |
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Small cell lung cancer (SCLC) is characterized by early and widespread metastases, but good responsiveness to both chemotherapy and radiotherapy. The percentage of long-term disease-free survival was reported in 1983 (1) to be in the range of 15–20% in cases of limited disease (LD) and only a few percent in those with extensive disease, and a recent report suggested an expected 5-year survival rate of
25% in cases with LD SCLC (2). Previous analyses of long-term disease-free survivors of SCLC (3,4) revealed that relapses usually occurred by 1.5 years after the beginning of combination chemotherapy. However, recent data indicate that as many as one-fourth of the patients who are disease-free at 30 months after the initial therapy develop late relapses (5). Furthermore, in his series, Vogelsang et al. (6) reported that 18 of the 25 long-term survivors (>2 years ) eventually showed relapse, sometimes as late as 8 years after the initial diagnosis. In 1993, we reported the course of a patient with SCLC who showed relapse 9.4 years after the initial treatment (7). In this paper, we report two cases of SCLC in whom relapse occurred after 10 or more years' disease-free survival, along with a review of the total of seven cases of SCLC reported until now, who developed a second SCLC or relapse after 10 years' disease-free survival. |
CASE REPORTS |
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TOPAbstractINTRODUCTIONCASE REPORTSDISCUSSIONReferences |
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CASE 1
A 61-year-old man participated in a mass screening for lung cancer by chest roentgenography (CXR) in June 1994. The Brinkman index was 1200, however, he stopped smoking after the first diagnosis. Fiberoptic bronchoscopy with transbronchial tumor biopsy confirmed the diagnosis of SCLC (Fig. 1a and b). The primary tumor was located in the B1+2 segment of the left upper lobe (Fig. 2a). Surgical resection of the left upper lobe was conducted, followed by combination chemotherapy with four cycles of cisplatin and etoposide. Pathologically, the tumor was determined to be stage IA SCLC and had no components of non-SCLC or large cell carcinoma with neuroendocrine properties.
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The patient underwent transurethral resection for early-stage bladder cancer (second malignancy) in January 2002 and received radiotherapy (75 Gy) for A2 (early) prostate carcinoma (third malignancy) in March 2004.
In June 2004, when he was 71 years old, a follow-up chest computed tomography (CT) and MRI (Fig. 2b) revealed para-aortic mediastinal lymphadenopathy (40 x 50 mm in size). The serum levels of pro-gastrin-releasing peptide, neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) were 360 pg/ml (normal range <46 pg/ml), 14.9 ng/ml and 1.4 ng/ml, respectively. The performance status on the Eastern Cooperative Oncology Group (ECOG) scale was zero, because he complained only of hoarseness and the serum lactate dehydrogenase (LDH) was normal. The standard staging procedures and upper gastro-intestinal screening by endoscopy revealed no evidence of metastases. Because of the poor pulmonary function of the patient and high metastatic potential of the disease, no surgery or chest irradiation was planned at this time. He was started on combination chemotherapy with irinotecan (CPT-11) at 60 mg/m2 on day 1 and etoposide at 80 mg/m2 on days 1–3, along with granulocyte-colony stimulating factor support on days 4–17 for one cycle, however, he developed severe neutropenia. The tumor regrew within 6 weeks of the treatment-free interval given to allow for his bone marrow recovery. He received CPT-11 at the dose of 50 mg/m2 alone bi-weekly and enjoyed prolonged partial response (PR). In March 2005, multiple bone metastases were observed, along with left cervical adenopathy. Aspiration biopsy of the cervical lymph nodes revealed the typical histologic features of SCLC (Fig. 1c). Brain metastasis occurred in July 2005, and in September 2005, the serum NSE level rose to 245 ng/ml. He died of cancer in October 2005.
CASE 2
In April 1987, a 72-year-old man visited our hospital with a month's history of productive cough and blood-streaked sputum. He had smoked one packet of cigarettes a day for 52 years; however, he stopped smoking at the first diagnosis of lung cancer. A CXR showed a right upper lobe mass, which was confirmed on chest CT (Fig. 3a). Fiberoptic bronchoscopy with tumor biopsy confirmed the diagnosis of SCLC (Fig. 4a and b). The patient was determined to have stage IB (T2N0M0) SCLC. Chemotherapy was administered with cyclophosphamide, doxorubicin and vincristine alternating with cisplatin-etoposide, for six cycles. Thereafter, sequential chest radiotherapy was administered.
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In September 1998, when he was 82 years old and 11.4 years had passed since the initial treatment of SCLC, the patient complained of shortness of breath on walking even as little as one block, and hemoptysis. His performance status on the ECOG scale was 3. The serum levels of LDH, NSE and CEA were all within normal range. The sputum cytology result was consistent with the diagnosis of SCLC (Fig. 4c). Chest CT revealed multi-stage mediastinal lymphadenopathy, especially on the ipsilateral side (Fig. 3b). There was no evidence of metastasis elsewhere, as confirmed by brain CT. Because of his poor performance status, the patient received two cycles of monotherapy with oral etoposide (50 mg/body/day for 14 days), with no shrinkage of the tumor. He died of worsened SCLC on 2 May 1999.
Table 1 shows a review of adequately documented cases of recurrence and/or second SCLC after 10 years of disease-free survival. All the patients received systemic combination chemotherapy followed by thoracic irradiation.
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DISCUSSION |
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TOPAbstractINTRODUCTIONCASE REPORTSDISCUSSIONReferences |
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Jacobs et al. (8) stated that there were continued relapses of disease until 39 months. Jacoulet et al. (5) reported that the risk of recurrence was <30% beyond 3 years and <10% beyond 5 years. In the treatment of SCLC, 5-year disease-free survival has usually been considered as a benchmark of cure (9,10). However, Niiranen (11) described a case with relapse at the primary site, in the central nervous system and in the skin 11 years after the diagnosis of SCLC.
Brigham et al. (12) estimated that the clinical doubling time of SCLC ranged from 25 to 160 days (median, 77 days; log mean, 81 days; arithmetic mean, 91 days) on the basis of chest radiographic findings. He suggested that highly effective therapy which reduces the residual tumor burden level to that approaching a single cell can be followed by disease-free intervals of more than 6 years before apparent clinical recurrence (>30 doublings). If the longer doubling time of 160 days were used for the calculation, potential relapse of SCLC may not be expected until 13 years after successful induction therapy with complete response as suggested by Al-Ajam et al. (10). It is usually difficult to ascertain whether a second SCLC is a late relapse of the first SCLC or a second primary tumor after a long disease-free survival. Some authors (9,13) suggested that the second diagnosis of SCLC after a long period of survival following the first diagnosis of SCLC should be considered as representing a second primary SCLC, whereas others (14,15) interpret it as representing a relapse of the first SCLC. The latter contention may be valid if the tumor arose at the same anatomic site as the initial SCLC, although the possibility of a new second primary tumor can still not be completely excluded. Kitamoto et al. (13) considered the second diagnosis of SCLC as a second malignancy, because the primary tumor was located in a different lobe of the lung in his patient. We believe that our patients may have had a relapse rather than a second primary tumor, because the second SCLC developed at the same site as the first tumor in one case, and in the ipsilateral mediastinal nodes in the other, and the specimens at diagnosis and at relapse showed an identical cytological or histological appearance in our patients (Figs 1 and 4).
Wistuba et al. (16) reported of observing genetic damage in the adjacent normal and hyperplastic bronchial epithelium in cases of SCLC. Tucker et al. (17) reported that continued smoking increased the risk of second primary cancers in patients treated for SCLC, and the cumulative risk of development of a second primary lung cancer made this cancer a common cause of death. Despite the decreasing incidence of recurrent SCLC with time, the longevity of long-term disease-free survivors continues to be compromised by increasing incidence of second primary smoking-related cancers. Since cigarette smoking cessation after successful therapy is associated with a decreased risk for a second smoking-related primary cancer, the simplest and most important intervention should be to encourage patients to quit smoking (18).
Although the standard therapy for late recurrent disease has not been established, retreatment with chemotherapy similar to the initial treatment (reinduction therapy) is reported to often achieve second responses up to 1 year or longer (19). Sekine et al. (20) also reported a relative good prognosis of patients after late relapse. The median survival time after relapse in their 13 patients was 7.4 months. This may be explained in part by good response to reinduction treatment in these patients or by very sluggish growth in these tumor cells.
Although only seven cases of late relapses after a 10-year disease-free survival have been reported until now, including our two patients, there is still a chance of such rare recurrence occurring beyond this interval. Therefore, careful follow-up is necessary to detect malignant lesions as early as possible in these long-term survivors.
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References |
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TOPAbstractINTRODUCTIONCASE REPORTSDISCUSSIONReferences |
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