In the clinical state of oligometastases or oligorecurrence, a transitional state between localized and widespread systemic disease, local control of the disease may yield improved systemic control. Radiotherapy may be a good means for controlling oligometastatic tumors, particularly in very old patients for whom surgery may be infeasible. A combination of systemic therapy and local therapy is necessary to prevent systemic progression. Some kinds of cancers found in the elderly are known to be somewhat indolent for systemic progression. So, for very old patients who refuse or cannot tolerate chemotherapy, the use of radical radiotherapy alone to treat oligorecurrences may be very helpful. We successfully treated an 87-year-old patient who had been diagnosed with oligorecurrences three times over six years with radiotherapy alone. The patient is now, about four years after his first radiotherapy for liver metastasis, alive without any evidence of cancer and with fully active performance status.
In the past, cancer metastasis was considered to be the last stage of life, as just one site of metastasis signaled hematogenous seeding, making locoregional therapy useless. About twenty years ago, the clinical state of oligometastatic disease was proposed by Hellman and Weichselbaum [
An 87-year-old man was admitted for radiation therapy to treat a liver metastasis from colon cancer in September 2010. At admission, he presented with discomfort in the right upper quadrant of his abdomen. His admission laboratory findings showed a total bilirubin of 0.8 mg/dL (normal, 0.2 to 1.3 mg/dL) and direct bilirubin of 0.3 mg/dL (normal, 0 to 0.3 mg/dL). Serum aspartate aminotransferase was 63 IU/L (normal, 0 to 37 IU/L), alanine aminotransferase was 48 IU/L (normal, 0 to 41 IU/L), lactic acid dehydrogenase was 1,152 IU/L (normal, 116 to 243 IU/L), alkaline phosphatase was 278 IU/L (normal, 35 to 129 IU/L), and GGT was 282 IU/L (normal, 8 to 61 IU/L). His carcinoembryonic antigen (CEA) level was markedly elevated to 1,736 ng/mL (normal 0 to 4.3 ng/mL). A whole body 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) revealed a hypermetabolic lesion in the right lobe of the liver (
Previously, the patient underwent low anterior resection for his sigmoid colon cancer in February 2007 in a different hospital. His pathological diagnosis was adenocarcinoma and its pathologic stage was T3N0M0. After the operation, his CEA level was normalized to 3.4 ng/mL. In September 2008 (about six years ago), his CEA level increased to 8.2 ng/mL from the 3.4 ng/mL postoperative level. Liver magnetic resonance image showed a 1.3 cm-sized metastatic mass in his S5 liver segment. Metastasectomy was recommended, but he refused and did not receive any anticancer treatments, except some herbal medications.
After the development of liver metastasis symptoms, the patient was admitted to our hospital. At first, we prescribed oral capecitabine (Xeloda) with radiation treatment for concurrent chemoradiation, but he stopped chemotherapy due to nausea and abdominal cramping after only a few days of treatment. Consequently, radiotherapy alone was performed for his liver metastasis from October 13, 2010 to December 2, 2010. The total radiation dose was 60 Gy in 30 fractions. The radiation treatment volume included the metastatic liver mass alone with an adequate margin. During radiotherapy, the patient's symptoms rapidly disappeared and his liver function rapidly normalized (
After the completion of the radiotherapy for his liver metastasis, we strongly recommended chemotherapy again, but the patient did not received further chemotherapy after receiving one cycle of fluorouracil-leucovorin chemotherapy in January 2011. He did not undergo any further chemotherapy.
In March 2013, a whole body FDG PET-CT scan showed a hot uptake, suggesting lung metastasis, was found in the medial portion of the patient's right upper lobe (RUL) of lung (
During an additional follow-up appointment, a 10 mm-sized nodule was found in RUL anterolateral subpleural portion of lung on CT scan at September 3, 2013, suggesting metastasis. The mass size increased to 13 mm on a subsequent CT scan on November 11, 2013 (
He is now, nearly four years from his first radiation treatment for liver metastasis, and after three subsequent curative dose radiation treatments, fully active with an Eastern Cooperative Oncology Group (ECOG) scale of 0 and without any evidence of cancer.
Also of note, the patient ate a continuous diet of Fucoidan products throughout his battle with cancer.
There were sequential changes in the concept of cancer progression.
Traditionally, the Halsted [
A subsequent hypothesis suggested that cancer is a systemic disease, and implied that small tumors are just an early manifestation of the systemic disease, which, if it is to metastasize, has already metastasized, and nodal involvement is not an orderly contiguous extension, but rather a marker of the distant disease. The systemic disease hypothesis was fully explicated with both laboratory and clinical studies by Fisher [
A third, 'Hellman and Weichselbaum' [
So, the implication is that oligometastatic disease is an intermediate state of cancer spread, between the localized disease and widespread metastases, and therefore, may be cured with metastasis-directed therapy.
Oligometastases, the state in which the patient shows distant relapses in only a limited number of regions, could be described as an uncontrolled primary site with several distant meta stases. Niibe and Hayakawa [
Niebe et al. [
The improvement of systemic chemotherapy, including molecular-targeted therapy, has allowed micro-metastases to be almost completely eradicated clinically. Theoretically, if several gross metastatic or recurrent sites could be eradicated by local therapy, these patients could be cured with con comitant systemic chemotherapy [
But for elderly patients, age-related biological changes are associated with an increased susceptibility to toxicity during chemotherapy [
In addition, some tumors in the elderly tend to be less aggressive. In some tumors types, such as breast cancer [
On the other hand, in a large Netherlands study, despite of the more frequent comorbidity and insufficient treatment in elderly patients, the relative survival was not lower for colon cancer, prostate cancer, or indolent non-Hodgkin lymphoma (NHL) than in younger patients [
According to a recent large epidemiologic study, the incidence and mortality of cancer usually decreases or plateaus at very old ages. The prevalence of various cancers usually decreases swiftly in people over the age of 90. When there was statistical power, the incidence normally peaked between ages 75 years and 90 years, dropping off abruptly afterward and trending toward zero among centenarians [
As described in this case report, our elderly patient with repeated oligorecurrence strongly refused chemotherapy. Consequently, in order to treat oligorecurrence without chemotherapy, we thought curative doses of radiation therapy may be helpful, especially in very old patients.
In our 87-year-old patient, single oligorecurrences occurred repeatedly three times in the liver and lung during a six-year period, and all the oligorecurrences were cured with curative doses of radiotherapy alone. Currently, nearly four years after his first radiation treatment for liver metastasis, the patient is alive, has a very good score on the ECOG scale (0), and has no evidence of any cancer.
No potential conflict of interest relevant to this article was reported.
The liver metastasis re gressed rapidly during liver radio therapy. Arrows denote liver meta stasis. (A) In pre-radiotherapy 18F-fluorodeoxy-glucose (FDG) posi tron emission tomo graphy/computed tomography (PET/CT) scan, huge hypermetabolic lesion was observed in liver. (B) Axial and (C) coronal view image of dynamic liver CT scan before liver radiotherapy showed 10-cm size ill-defined inhomogeneous and partially-calcified mass in right inferior lobe of liver. CT scan also showed occlusions of posterior branch and compression of anterior branch of right portal vein was also observed on CT scan. (D) FDG PET/CT scan at the latter part of radiotherapy showed the hypermetabolic lesion in liver was markedly decreased.
Carcinoembryonic antigen (CEA) level rapidly decreased after radiotherapy for liver metastasis. Time sequences 1, after curative resection of primary colon cancer; 2, at first detection of liver metastasis (September 2008); 3, immediately before liver radiotherapy (September 2010); 4, three months after liver radiotherapy (March 2011); 5, one and half years after liver radiotherapy (December 2012); 6, in recent time (July 2014).
First lung metastasis completely regressed with radiotherapy. Arrows denote first lung metastasis. (A) Pre-radiotherapy 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan showed a hypermetabolic lesion in right upper lobe (RUL) of lung. (B) Pre-radiotherapy chest CT scan showed a 2-cm size metastatic mass in RUL of lung. (C) In postradiotherapy FDG PET/CT scan, no abnormal hypermetabolic lesion was observed.
Second lung metastasis completely regressed with radiotherapy. Arrows denote second lung metastasis. (A) Pre-radiotherapy chest computed tomography (CT) scan showed increased size of new right upper lobe (RUL) nodule compared with previous CT scan (10 → 13 mm) suggesting aggravated single hematogenous lung metastasis. (B) In post-radiotherapy chest CT scan, a nodule in RUL of lung disappeared and subpleural consolidation with focal ill-defined ground-glass opacity suggesting radiation change appeared in posterolateral portion of RUL.
Changes in the liver function during and after radiotherapy (unit, IU/L)
AST, aspartate transaminase; ALT, alanine transaminase; LDH, lactic acid dehydrogenase; ALP, alkaline phosphatase; GGT, gamma-glutamyl transpeptidase.