Investigation of radiation therapy for gynecologic cancer patients with supraclavicular lymph node metastases

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F
or patients with gynecologic cancer, the pattern of lymphatic spread appears to be stepwise from the pelvic lymph nodes to the para-aortic lymph nodes (PANs) and ultimately to the supraclavicular lymph nodes (SCNs) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10) .The prognosis is dismal in patients with gynecologic cancer with SCN metastases, and patients with symptoms of pain experience a decline in their quality of life.However, few studies have so far been performed to determine the benefits of treatment for SCN metastases in this population.Therefore, we retrospectively evaluated the benefits and adverse events of radiotherapy (RT) for SCN metastases.

MATERIAL AND METHODS
We retrospectively investigated the local control rate, overall survival (OS) rate and palliative effect of RT for patients with gynecologic cancer with SCN metastases.We reviewed the treatment outcomes of 18 gynecologic cancer patients with SCN metastases treated by RT between 2004 and 2014 at our hospital.The patient characteristics are shown in Tab. 1.

Statistics
The following analyses were used in this study: the Response Evaluation Criteria In Solid Tumors (RECIST) to evaluate the tumor response; the Common Terminology Criteria for Adverse Events (CTCAE), ver.4.0, to evaluate adverse events; and the Kaplan-Meier method to evaluate the OS rate.Significant differences were evaluated using the log-rank test.

Palliative effect on the symptoms at SCN
There were 7 symptomatic patients.Of these patients, 2 developed symptoms of pain, which was relieved following therapy (2/2; 100%).Edema and swelling were also present in these patients and subsequently improved in 6 out of 7 patients (85.7%) following therapy.Eleven asymptomatic patients did not develop any symptoms during the follow-up period.

CTCAE grades 2-5 acute toxicities
CTCAE grade 2 toxicities were found in 5 out of 18 patients; 2 patients had dermatitis and 4 had hematologic toxicities.Grade 3 toxicities were found in 3 out of 18 patients, all of whom had hematologic toxicities.None of the patients developed grade 4 or 5 toxicities.Prognostic factors are shown in Tab. 2.

Recurrence type
Patients with distant metastasis limited to the SCN and/or PAN had significantly better prognoses compared to patients with distant metastasis beyond the SCN and/or to other organs during SCN treatment.Furthermore, the extensive type was significantly associated with a decreased overall survival (p = 0.0305).

Overall survival
Lee et al. reported that RT with chemotherapy as active therapy may provide favorable results for cervical cancer patients with SCN metastases but no evidence of distant metastasis (7) .Furthermore, Hong et al. reported that patients with SCN metastases had a longer survival time than those with other metastases (except PAN) (8) .The median survival time was reported to be 7.5 months in 14 cervical cancer patients with SCN metastases (2) .Lee et al. reported that a cervical cancer patient with primary SCN metastasis was not incurable (7) .a standardized uptake value (SUV) of fluorodeoxyglucose positron emission tomography (FDG-PET) of <4.3 or >8 were significant adverse prognostic factors (3) .Our investigation showed similar results.In particular, if the recurrence type is limited, then it may be curable using additional radiotherapy for SCN.Furthermore, even if the disease is extensive, it is possible to control the pain, swelling and redness, thereby improving the patient's quality of life.Cervical cancer with SCN metastasis is a localized disease and we speculate that aggressive therapy, including systemic therapy, may improve the outcomes due to the patterns of lymphatic spread in cervical cancer.Shin and colleagues reported that patients with SCN involvement treated with concurrent chemoradiotherapy showed favorable survival outcomes (3-year OS rate of 63.6% and 3-year progression-free survival rate of 56.4%) with acceptable toxicities (10) .However, randomized control trials with a larger cohort size are necessary to determine the role of SCN RT.

CONCLUSION
The prognosis is dismal in patients with gynecologic cancer with SCN metastases.However, RT for SCN is effective as palliative irradiation because it had a good 2-year local control rate (75.8%), improved the patients' symptoms and asymptomatic patients did not develop any symptoms during the follow-up period.
Ho et al.reported that a latency period of <2 years, SCC-Ag levels of 4 ng/mL, recurrence beyond the SCN, and