Postoperative radiotherapy alone is as effective as postoperative chemoradiotherapy in patients with pT4aN0 gingival cancer with negative surgical margins.

Background and purpose: This study compared the survival outcomes following postoperative chemoradiotherapy (CCRT) and postoperative radiotherapy (RT) alone for patients with gingival cancer with negative surgical margins and only bone invasion. Materials and methods: Of the 2579 gingival cancer cases reviewed from 2002 to 2018, 156 were enrolled in the study (CCRT: 63 patients; RT: 93 patients). The primary endpoints were the impact of adjuvant treatment (RT vs. CCRT) on overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS). Subgroup analyses were conducted based on surgical margins (<5 mm vs. ≥ 5 mm) and different adjuvant treatments (RT vs. CCRT). Results: Median follow-up time, age, and invasion depth were 88.5 months, 57 years, and 14 mm, respectively. More patients undergoing adjuvant CCRT had surgical margins < 5 mm (47.6% vs. 21.5%, p < 0.01) than those undergoing RT. No significant difference was observed in the 5-year OS, LRRFS, and DMFS of patients undergoing adjuvant RT and CCRT. Although adjuvant RT alone and CCRT provided similar local control for patients with surgical margins ≥ 5 mm, worse LRRFS trends were observed in patients with surgical margins < 5 mm (hazards ratio, 6.15, 95% confidence interval 0.92-41.13, p = 0.06). Conclusion: Postoperative RT alone may be effective for patients with gingival cancer with negative surgical margins (≥5 mm) and only bone invasion, while postoperative CCRT may result in better LRRFS than RT alone for patients with surgical margins < 5 mm.

Long-term treatment outcomes/toxicities of definite chemoradiotherapy (intensity-modulated radiation therapy) for early-stage "bulky" cervical cancer and survival impact of histological subtype.

BACKGROUND: To investigate the long-term treatment outcomes of early stage bulky cervical cancer treated with definite chemoradiotherapy (CCRT) using intensity-modulated radiotherapy (IMRT) followed by intracavity brachytherapy (ICRT) and the impact of histologic subtype on survival. METHODS: From 2004 to 2016, 126 patients with FIGO stage IB2-IIB bulky (≥4 cm) cervical cancer treated with CCRT followed by ICRT were retrospectively reviewed. Long-term treatment-related acute/late toxicities and treatment outcomes including overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were reported. Different histologic subtype between squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (AC/ASC)) of uterine cervix were also compared. RESULTS: Median follow-up time for alive patients was 117 months. The 5-year OS, LRRFS and DMFS were 75.3%, 87.8% and 75.6%, respectively. The most common ≥ grade 3 acute toxicity was hematologic toxicity (41.3%). The rates of ≥ grade 3 late toxicities were 4% of proctitis, 0.8% of urethral stricture and 0.8% of radiation dermatitis (peri-anal skin necrosis and gangrene). The 5-year OS/LRRFS/DMFS for SCC and AC/ASC were 81.7%/93.7%/81.5% and 51.9%/65.8%/53.5%, respectively (all log-rank p < 0.05). The AC/ASC histology was an independent prognostic factor for worse OS, LRRFS, and DMFS (All p < 0.05). CONCLUSION: After long-term follow up, definite CCRT using IMRT followed by ICRT is a feasible treatment with favorable acute and late treatment toxicities for patients with early stage bulky cervical cancer. This treatment outcomes were excellent for "bulky" FIGO stage IB2-IIB SCC of the uterine cervix but seemed insufficient for AC/ASC of uterine cervix.

Adjuvant whole breast radiotherapy with simultaneous integrated boost to tumor bed with intensity modulated radiotherapy technique in elderly breast cancer patients.

BACKGROUND: Adjuvant whole breast radiotherapy is the standard of care for breast cancer patients after partial mastectomy. Intensity-modulated radiation therapy (IMRT) has been reported to reduce acute toxicities compared to conventional radiotherapy. IMRT with simultaneous integrated boost (SIB) technique can deliver higher doses to tumor bed and irradiate whole breast with a lower dose level to shorten overall treatment duration. This study presents the long-term results of adjuvant IMRT with SIB in elderly breast cancer patients who received partial mastectomy. METHODS: From January 2007 to January 2018, 93 elder breast cancer patients (≥65-year-old) who received IMRT with SIB technique after partial mastectomy were reviewed retrospectively. The axillary areas were managed with either sentinel lymph node biopsies or axillary lymph node dissection. The dose to whole breast was 50.4 Gy in 28 fractions in all patients and the dose to tumor bed was 61.6 to 66.4 Gy in 28 fractions. The primary end point is locoregional control. Secondary end points include: overall survival, breast cancer-specific survival, distant-metastases-free survival, disease-free survival, and acute and chronic toxicities. RESULTS: The median follow-up was 56.1 months. One patient had ipsilateral breast tumor recurrence, 3 patients had regional lymph node recurrence, and 9 patients had distant metastases. Death occurred in 5 patients, including 3 patients died of breast cancer progression. Five-year overall survival is 96.3% and 5-year locoregional recurrence-free survival is 96.4%. The 5-year breast cancer specific survival and 5-year distant metastases-free survival is 97.5% and 87.2%, respectively. Seven patients developed second primary cancer after RT. Eighty-one point seven percent patients had acute grade 1 dermatitis while 18.3% suffered from grade 2 dermatitis. The incidence of grade 1 pneumonitis and grade 1 stomatitis was 4.3% and 8.6%, respectively. CONCLUSIONS: Adjuvant IMRT with SIB technique is a safe and effective treatment strategy for elderly breast cancer patients after partial mastectomy.

Definite chemoradiotherapy is a competent treatment option in FIGO stage IB2 cervical cancer compared with radical surgery +/- neoadjuvant chemotherapy.

BACKGROUND: To compare the treatment outcomes of different treatment modalities for International Federation of Gynecology and Obstetrics (FIGO) stage IB2 cervical cancer. METHODS: From January 2002 to July 2016, 91 patients with FIGO stage IB2 squamous cell carcinoma, adenocarcinoma or adenosquamous carcinoma of the cervix were enrolled. All of them received one of the following treatment modalities, including intensity-modulated radiotherapy (IMRT) with concurrent platinum-based chemotherapy (CCRT group, n = 27), radical surgery with or without adjuvant treatment (RH group, n = 25), or neoadjuvant chemotherapy followed by radical surgery with or without adjuvant treatment (NACT group, n = 39). Overall survival (OS), disease free survival (DFS), loco-regional failure-free survival (LRFFS) and distant metastasis-free survival (DMFS) were compared among the three different groups. RESULTS: The median follow up durations were 63.3 months for the CCRT group, 83.5 months for the NACT group, and 89.8 months for the RH group, respectively. The 5-year OS, DFS, LRFFS and DMFS for CCRT group vs. NACT group vs. RH group were 80.1% vs. 94.1% vs. 93.8% (p = 0.197), 79.5% vs. 79.3% vs. 91.0% (p = 0.401), 88.1% vs. 81.8% vs. 95.8% (p = 0.253), and 83.3% vs. 88.8% vs. 95.2% (p = 0.422). No significant prognostic factor was found in OS. Age > 48 was significant in predicting poor DFS and DMFS. The non-squamous cell carcinoma was a significant predictor of poor DFS, LRFFS and DMFS. CONCLUSION: CCRT is a feasible therapeutic option with acceptable acute and chronic treatment-related toxicities for patients who cannot tolerate radical surgery or neoadjuvant chemotherapy.

Definite intensity-modulated radiotherapy with concurrent chemotherapy more than 4 cycles improved survival for patients with locally-advanced or inoperable esophageal squamous cell carcinoma.

We investigated which prognostic factor could improve survival for esophageal cancer patients who received definite concurrent chemoradiation (CCRT). Eighty patients with age ≥18, Karnofsky Performance Scale (KPS) ≥ 60, and clinical stage T1-4N0-3M0 esophageal squamous cell carcinoma were enrolled from July 2004 to December 2015. They underwent definite intensity-modulated radiotherapy (IMRT) with or without simultaneous integrated boost to the primary tumor, and reception of concurrent chemotherapy ≥ 1 cycle. The primary endpoints were overall survival (OS), locoregional progression-free survival (LRPFS) and distant metastasis-free survival (DMFS). The median follow-up duration for alive patients was 21.5 months. The rates of 2-, 3- and 5-year OS/LRPFS/DMFS were 23.8%/53.5%/49.3%, 19.1%/44.6%/49.3%, and 13.0%/44.6%/43.9%, respectively. Only the non-clinical complete response (non-cCR) after CCRT was an independent poor prognostic factor in OS (HR 3.101, 95% CI 1.535-6.265, p = 0.0016). Radiation dose >50.4 Gy and chemotherapy ≥4 cycles significantly predicted better LRPFS (p = 0.0361 and 0.0163, respectively). Poorly differentiated tumor and stage III disease have poor DMFS (p = 0.0336 and 0.0411, respectively), and chemotherapy ≥ 4 cycles was a better predictor (p = 0.0004). In subgroup analysis, patients who received radiation dose ≤50.4 Gy with concurrent chemotherapy ≥4 cycles had the best survival outcome with 1-, 2-, 3- and 5-year survival rates of 73.7%, 39.4%, 31.5% and 17.5%, respectively. In conclusion, definite radiotherapy with concurrent chemotherapy ≥4 cycles improved the survival for patients with inoperable or locally-advanced esophageal squamous cell carcinoma.

Role of adjuvant radiotherapy in FIGO stage IIIC endometrial carcinoma: Treatment outcomes and prognostic factors in 52 irradiated patients.

BACKGROUND: To retrospectively review the postoperative radiotherapy treatment outcomes and the prognostic factors for the International Federation of Gynecology and Obstetrics (FIGO) stage IIIC endometrial carcinoma. METHODS: Fifty-two patients who were newly diagnosed and previously untreated FIGO stage IIIC endometrial carcinoma over a 33-year period (September 1983 to April 2015) were retrospectively reviewed. They had received radical surgery followed by adjuvant radiotherapy with or without adjuvant chemotherapy. Those excluded patients had initial distant metastasis disease, palliative intent or incomplete adjuvant radiotherapy. Different subgroups of the stage III patients were compared statistically in terms of their rates of overall survival (OS), loco-regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). RESULTS: The median follow up duration was 51.5 months (range, 5-298). The loco-regional recurrence was found in 4 patients and distant metastasis in 15 patients. Comparing stage IIIC1 vs. IIIC2 patients, their 5-year OS were 69.9% vs. 55% (p = 0.0954), LRRFS 90.3% vs. 94.4% (p = 0.6151), and DMFS 82.5% vs. 53.3% (p = 0.0080). The FIGO stage was a significant factor for DMFS (hazard ratio [HR], 5.440, 95% confidence interval [95% CI] 1.379-21.451, p = 0.0155), but only marginal for OS (HR, 2.137, 95% CI 0.930-4.913, p = 0.0738). The ECOG performance status was marginal significant for DMFS (HR, 4.777, 95% CI 0.976-23.378, p = 0.0536). CONCLUSION: Adjuvant radiotherapy decreased loco-regional recurrence and had good local control in FIGO stage IIIC endometrial carcinoma. The stage IIIC2 patients showed a greater tendency of distant metastases and poorer overall survival rate when compared to patients of stage IIIC1.

Prognostic impact of adjuvant chemotherapy in high-risk nasopharyngeal carcinoma patients.

OBJECTIVES: To investigate the prognostic impact of adjuvant chemotherapy (AdjCT) in patients with high-risk nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: A total 403 NPC patients with at least one of the following criteria (1) neck node>6cm; (2) supraclavicular node metastasis; (3) skull base destruction/intracranial invasion plus multiple nodes metastasis; or (4) multiple neck nodes metastasis with one of nodal size>4cm were retrospectively reviewed. All patients finished curative radiotherapy±neoadjuvant/concurrent chemotherapy. Post-radiation AdjCT consisted of tegafur-uracil (two capsules twice daily) for 12months. We analyzed the treatment outcome between patients with (n=154) and without (n=249) AdjCT. RESULTS: Baseline patient characteristics at diagnosis (age, gender, pathological type, performance status, T-classification, N-classification, and overall stage) were comparable in both arms. After a median follow-up of 72months for surviving patients, 31.8% (49/154) and 42.2% (105/249) in patients with and without AdjCT developed tumor relapse respectively (P=0.0377). AdjCT improved both overall survival (HR 1.89, 95% CI 1.37-2.61, P=0.0001) and progression-free survival (HR 1.42, 95% CI 1.03-1.96, P=0.0322). There were significant reduction in distant failures (P=0.0016) but not in local (P=0.8587) or regional (P=0.8997) recurrences for patients who received AdjCT. CONCLUSION: AdjCT can reduce distant failure and improve overall survival in high-risk NPC patients after curative radiotherapy±neoadjuvant/concurrent chemotherapy.

Long-term clinical outcome in nasopharyngeal carcinoma patients with post-radiation persistently detectable plasma EBV DNA.

PURPOSE: To investigate the long-term clinical outcome of nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma EBV (pEBV) DNA after curative radiotherapy (RT). RESULTS: The post-RT pEBV DNA levels were very lower copy number (median 21, interquartile range 8-206 copies/ml). After long-term follow-up, the relapse rate was 64.8%, the median time to progression 20 months, and 5-year overall survival (OS) 49.6%. Thirty-two of 39 (82.1%) patients with high viral load (≥ 100 copies/ ml) developed tumor relapse, whereas 57.0% (49/86) patients with low viral load (< 100 copies/ml) had tumor relapse (P = 0.0065). The 5-year OS rates were 20.5% and 62.9% for patients with viral load ≥ and < 100 copies/ml (median survival, 20 vs. 100 months; P < 0.0001). Patients who received adjuvant chemotherapy (AdjCT) experienced significant reduction in distant failures (66.2% vs. 31.6%; P = 0.0001) but similar locoregional recurrences (P = 0.2337). The 5-year OS rates were 69.4% for patients who received AdjCT compared with 33.2% for those of without AdjCT (median survival, 111 vs. 32 months; P < 0.0001). METHODS: We screened 931 newly diagnosed NPC patients who finished curative RT and found 125 patients (13.4%) with detectable pEBV DNA one week after RT. The clinical characteristics, treatment modality, subsequent failure patterns and survivals were analyzed. CONCLUSIONS: NPC patients with persistently detectable pEBV DNA after curative RT have a higher rate of treatment failure and poor survivals. Levels of the post-RT pEBV DNA and administration of AdjCT affect the final outcome significantly.

Feasibility of intensity-modulated radiotherapy for esophageal cancer in definite chemoradiotherapy.

BACKGROUND: Esophageal cancer is a highly lethal malignancy, and its treatment has undergone a major evolution over the past 15 years. The objective of this study was to report our experience on the efficacy of definite chemoradiotherapy with the intensity-modulated radiotherapy (IMRT) technique in treating locally advanced esophageal cancer. METHODS: From September 2004 to November 2011, 39 patients with biopsy-proven esophageal cancer, clinical stage T1-4N0-3M0 according to the American Joint Committee on Cancer 7(th) edition were enrolled. In these enrolled cases, either the tumor was unresectable or the patients refused surgery. All patients received a total radiation dose of 40-56 Gy in 20-28 fractions using IMRT planning. Five to seven radiation beam angles were designed according to the specific shape of the clinical target volume (CTV) and were delivered by a linear accelerator with photons of 6-10 MV energy. The gross tumor volume, CTV, planning target volume, and the organs at risk were outlined, and the homogeneity index (HI) and the conformity index (CI) were calculated. The treatment-related toxicities were also reviewed. RESULTS: The mean follow-up time was 22.4 months (range, 2.0-91.0 months). The 2- and 3-year overall survival rates were 30% and 28%, respectively. The most common Grade 3/4 toxicity was hematologic toxicity (43.6%). The IMRT plans showed high-dose homogeneity to the target, with a calculated HI of 0.9. The calculated CI of 0.8 also showed high conformity treatment dose to target within an acceptable dose range. For the total lungs, the average mean dose was 1313.7 cGy. The V5 and V20 of the total lungs were 67.8% and 23.4%, respectively. For the heart, the average mean dose was 2319.2 cGy. The V30 and V35 of the heart were 30.2% and 21.5%, respectively. CONCLUSION: Concurrent chemoradiotherapy using the IMRT technique for treating locally advanced unresectable esophageal cancer is feasible, with better conformity of target volume as well as improved sparing of organs at risk.