Re-irradiation with Moderate Hypo-fractionation Using Intensity Modulated Photon or Proton Radiation Therapy in Locally Recurrent Squamous Cell Carcinoma of Nasopharynx / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to analyze the treatment outcomes of locally recurrent nasopharyngeal cancer (NPC) patients following moderate hypo-fractionation re-irradiation (re-RT). @*Materials and Methods@#Sixty locally recurrent NPC patients underwent hypo-fractionation re-RT. Forty-eight point three percentage had rT3-4, and 30.0% did keratinizing squamous cell carcinoma. Intensity-modulated radiation therapy (IMRT), with or without intensity-modulated proton therapy (IMPT), was used in 66.7% of patients. @*Results@#With the median follow-up of 22 months (range, 2 to 254 months), 31 patients (51.7%) died, 38 (63.3%) developed further treatment failure, and 30 (50.0%) developed ≥ grade 3 toxicity (including seven grade 5) at time of analysis. The 2- and 5-year rates of overall survival, local failure-free survival, and ≥ grade 3 toxicity-free survival were 57.9% and 45.8%, 64.1% and 52.5%, and 54.8% and 44.9%, respectively. In multivariate analyses, worse factors for overall survival (OS) were iT3-4 (p=0.010) and age at re-RT ≥ 53 years (p=0.003), those for local failure-free survival (LFFS) were rT3-4 (p=0.022) and rN0-1 (p=0.035), and those for toxicity-free survival (TFS) were iT3-4 (p=0.020) and re-IMRT/IMPT (p=0.030), respectively. Cumulative dose or fraction size ≥ 3 Gy at re-RT, however, showed no significance for OS, LFFS and TFS. @*Conclusion@#Current re-RT with modern RT techniques by moderate hypo-fractionation scheme seemed feasible in treating locally recurrent NPC patients.

Increased Risk of Diabetes after Definitive Radiotherapy in Patients with Indolent Gastroduodenal Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aimed to evaluate the effect of radiotherapy (RT) on the risk of diabetes by assessing hemoglobin A1c (HbA1c) levels in patients with gastroduodenal indolent lymphoma. @*Materials and Methods@#This retrospective study included patients with stage I extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue or follicular lymphoma of the gastroduodenal region who were treated with Helicobacter pylori eradication and/or RT between 2000 and 2019 in our institution. Of total 79 patients with HbA1c test, 17 patients received RT (RT group), while 62 patients did not receive RT (control group). A diabetes-associated event (DAE) was defined as a ≥ 0.5% increase in HbA1c levels from baseline, and diabetes event (DE) were defined as HbA1c level of ≥ 6.5%. @*Results@#During the median follow-up of 49 months, no local failure occurred after RT and no patients died of lymphoma. The RT group had significantly higher risk for DAEs on univariable analysis (hazard ratio [HR], 4.18; 95% confidence interval [CI], 1.64 to 10.66; p < 0.01) and multivariable analysis (HR, 3.68; 95% CI, 1.42 to 9.56; p=0.01). Further, the DE risk was significantly higher in the RT group than in the control group (HR, 4.32; 95% CI, 1.08 to 17.30; p=0.04) and in patients with increased baseline HbA1c levels (HR, 35.83; 95% CI, 2.80 to 459.19; p=0.01). On multivariable analysis, RT significantly increased the risk of DEs (HR, 4.55; 95% CI, 1.08 to 19.19; p=0.04), even after adjusting baseline HbA1c level (HR, 40.97; 95% CI, 3.06 to 548.01; p=0.01). @*Conclusion@#Patients who received RT for gastroduodenal indolent lymphoma had an increased risk of diabetes compared to those who did not.

Feasibility of Selective Neck Irradiation with Lower Elective Radiation Dose in Treating Nasopharynx Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study aimed to report the clinical outcomes following selective neck irradiation (SNI) with lower elective radiation therapy (RT) dose in treating nasopharyngeal cancer (NPC) patients. MATERIALS AND METHODS: A total of 347 NPC patients received definitive RT according to our SNI policy and were retrospectively analyzed. The clinical target volumes (CTVs) were subdivided into CTV at high risk (CTV-HR) and CTV at low risk (CTV-LR). The typical doses to gross tumor volume (GTV), CTV-HR, and CTV-LR were 68.4-70.0 Gy, 54.0-60.0 Gy, and 36.0 Gy. RESULTS: With the median follow-up of 68.1 months (range, 2.3 to 197.1 months), the 5-year rates of loco-regional control and progression-free survival in all the patients were 85.0% and 70.8%, respectively. Thirty patients developed regional failure and the regional control rates at 3 and 5 years were 92.6% and 91.4%, respectively. The sites of regional failure in relation to the target volume were exclusively inside GTV/CTV-HR in 20, inside and outside GTV/CTVHR in three, and exclusively outside GTV/CTV-HR in seven, which were 5.7%, 0.9%, and 2.0% of total patients, respectively. CONCLUSION: The clinical outcomes by the current SNI policy were feasible and comparable to those following classic elective nodal irradiation policy.

Salvage Concurrent Chemo-radiation Therapy for Loco-regional Recurrence Following Curative Surgery of Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study is to report clinical outcomes of salvage concurrent chemo-radiation therapy (CCRT) in treating patients with loco-regional recurrence (LRR) following initial complete resection of non-small cell lung cancer. MATERIALS AND METHODS: Between February 2004 and December 2016, 127 patients underwent salvage CCRT for LRR. The median radiation therapy (RT) dose was 66 Gy and clinical target volume was to cover recurrent lesion with margin without elective inclusion of regional lymphatics. Majority of patients (94.5%) received weekly platinum-based doublet chemotherapy during RT course. RESULTS: The median follow-up time from the start of CCRT was 25 months. The median survival duration was 49 months, and overall survival (OS) rates at 2 and 5 years were 72.9% and 43.9%. The 2- and 5-year rates of in-field failure-free survival, distant metastasis free survival, and progression free survival were 82.4% and 73.8%, 50.4% and 39.9%, and 34.6% and 22.3%, respectively. Grade ≥ 3 radiation-related esophagitis and pneumonitis occurred in 14 (11.0%) and six patients (4.7%), respectively. On both univariate and multivariate analysis, higher biologically equivalent dose (BED₁₀) (≥ 79.2 Gy₁₀ vs. 80 cm³; HR, 0.403), and longer disease-free interval (> 1 year vs. ≤ 1 year; HR, 0.489) were significantly favorable factors for OS. CONCLUSION: The current study has demonstrated that high dose salvage CCRT focused to the involved lesion only was highly effective and safe. In particular, higher BED₁₀, smaller CTV, and longer disease-free interval were favorable factors for improved survival.

Tumor Volume Reduction Rate during Adaptive Radiation Therapy as a Prognosticator for Nasopharyngeal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The purpose of this study is to evaluate the prognostic significance of the tumor volume reduction rate (TVRR) measured during adaptive definitive radiation therapy (RT) for nasopharyngeal cancer (NPC). MATERIALS AND METHODS: We reviewed the RT records of 159 NPC patients treated with definitive RT with or without concurrent chemotherapy between January 2006 and February 2013. Adaptive re-planning was performed in all patients at the third week of RT. The pre- and mid-RT gross tumor volumes (GTVs) of the primary tumor and the metastatic lymph nodes were measured and analyzed for prognostic implications. RESULTS: After a median follow-up period of 41.5 months (range, 11.2 to 91.8 months) for survivors, there were 43 treatment failures. The overall survival and progression-free survival (PFS) rates at 5 years were 89.6% and 69.7%, respectively. The mean pre-RT GTV, mid-RT GTV, and TVRR were 45.9 cm3 (range, 1.5 to 185.3 cm3), 26.7 cm3 (1.0 to 113.8 cm3), and -41.9% (range, -87% to 78%), respectively. Patients without recurrence had higher TVRR than those with recurrence (44.3% in the no recurrence group vs. 34.0% in the recurrence group, p=0.004), and those with TVRR > 35% achieved a significantly higher rate of PFS at 5 years (79.2% in TVRR > 35% vs. 53.2% in TVRR ≤ 35%; p < 0.001). In multivariate analysis, TVRR was a significant factor affecting PFS (hazard ratio, 2.877; 95% confidence interval, 1.555 to 5.326; p=0.001). CONCLUSION: TVRR proved to be a significant prognostic factor in NPC patients treated with definitive RT, and could be used as a potential indicator for early therapeutic modification during the RT course.

Clinical outcomes of stereotactic body radiotherapy for spinal metastases from hepatocellular carcinoma

PURPOSE: To investigate the outcomes of patients with spinal metastases from hepatocellular carcinoma (HCC), who were treated by stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: This retrospective study evaluated 23 patients who underwent SBRT from October 2008 to August 2012 for 36 spinal metastases from HCC. SBRT consisted of approximately 2 fractionation schedules, which were 18 to 40 Gy in 1 to 4 fractions for group A lesions (n = 15) and 50 Gy in 10 fractions for group B lesions (n = 21). RESULTS: The median follow-up period was 7 months (range, 2 to 16 months). Seven patients developed grade 1 or 2 gastrointestinal toxicity, and one developed grade 2 leucopenia. Compression fractures occurred in association with 25% of the lesions, with a median time to fracture of 2 months. Pain relief occurred in 92.3% and 68.4% of group A and B lesions, respectively. Radiologic response (complete and partial response) occurred in 80.0% and 61.9% of group A and B lesions, respectively. The estimated 1-year spinal-tumor progression-free survival rate was 78.5%. The median overall survival period and 1-year overall survival rate were 9 months (range, 2 to 16 months) and 25.7%, respectively. CONCLUSION: SBRT for spinal metastases from HCC is well tolerated and effective at providing pain relief and radiologic response. Because compression fractures develop at a high rate following SBRT for spinal metastases from primary HCC, careful follow up of the patient is required.

High Dose Involved Field Radiation Therapy as Salvage for Loco-Regional Recurrence of Non-Small Cell Lung Cancer

PURPOSE: To determine the effectiveness of salvage radiation therapy (RT) in patients with loco-regional recurrences (LRR) following initial complete resection of non-small cell lung cancer (NSCLC) and assess prognostic factors affecting survivals. MATERIALS AND METHODS: Between 1994 and 2007, 64 patients with LRR after surgery of NSCLC were treated with high dose RT alone (78.1%) or concurrent chemo-radiation therapy (CCRT, 21.9%) at Samsung Medical Center. Twenty-nine patients (45.3%) had local recurrence, 26 patients (40.6%) had regional recurrence and 9 patients (14.1%) had recurrence of both components. The median RT dose was 54 Gy (range, 44-66 Gy). The radiation target volume included the recurrent lesions only. RESULTS: The median follow-up time from the start of RT in survivors was 32.0 months. The rates of in-field failure free survival, intra-thoracic failure free survival and extra-thoracic failure free survival at 2 years were 52.3%, 33.9% and 59.4%, respectively. The median survival after RT was 18.5 months, and 2-year overall survival (OS) rate was 47.9%. On both univariate and multivariate analysis, the interval from surgery till recurrence and CCRT were significant prognostic factors for OS. CONCLUSION: The current study demonstrates that involved field salvage RT is effective for LRR of NSCLC following surgery.

Incidence of Brain Metastasis and Related Subtypes in Patients with Breast Cancer Receiving Adjuvant Radiation Therapy after Surgery / 한국유방암학회지

PURPOSE: To assess the incidence of brain metastasis in patients with breast cancer receiving surgery and adjuvant radiotherapy (RT) and to evaluate subtypes associated with brain metastasis. METHODS: We retrospectively reviewed the medical records of 1,000 patients with breast cancer who were treated with surgery and adjuvant RT for a cure between January 2001 and July 2005 at Samsung Medical Center. Seventy-one patients received neoadjuvant chemotherapy before surgery. The pathological stage was I in 430 patients, II in 327, and III in 243. We divided the patients into three subtypes according to immunohistochemistry: triple negative (TN, 245 patients), human epidermal growth factor 2 (HER2) enriched (HE, 166 patients) and positive estrogen receptor or progesterone receptor without HER2 overexpression (EP, 589 patients). The median follow up time was 72 months after surgery. RESULTS: Locoregional failure-free survival rate and distant metastasis-free survival rate at 5 years were 92.8% and 86.1%, respectively. The disease free survival rate and overall survival rate at 5 years were 84.6% and 94.7%, respectively. Thirty-nine patients had brain metastasis, and the brain metastasis-free survival rate at 5 years was 97.2%. A univariate analysis showed that younger age, neoadjuvant chemotherapy, modified radical mastectomy, advanced pathological stage and the TN and HE subtypes were significant risk factors for brain metastasis. A multivariate analysis revealed that age, neoadjuvant chemotherapy, pathological stage and the TN and HE subtypes were statistically significant factors for brain metastasis. CONCLUSION: The cumulative incidence of brain metastasis was 3.9% after curative treatment. If patients have a clinically suspicious symptoms suggesting brain metastasis, clinicians should be aware that an early brain imaging work up and management are necessary. Because patients with the TN or HE subtypes accompanied by younger age and advanced pathological stage have increased brain metastasis (>10%), annual regular imaging follow-up may be recommended for these high risk patients.

Treatment Results of Major Salivary Gland Cancer by Surgery with or without Postoperative Radiation Therapy

OBJECTIVES: This is to report treatment results of major salivary gland cancer by surgery with or without postoperative radiation therapy (PORT). METHODS: Between March 1995 and January 2006, 94 patients with primary major salivary cancer underwent curative surgical resection at Samsung Medical Center. The parotid gland was the most commonly involved (73, 77.7%), followed by the submandibular and the sublingual. Neck dissection was added in 28 patients, and PORT was individually recommended to those with risk factors. Seventy-five (79.8%) patients received PORT. PORT volume included primary tumor bed and pathologically involved regional lymphatics, and no additional effort was made for elective nodal irradiation. The median total doses were 56.0 Gy to primary site and 58.7 Gy to regional lymphatics. RESULTS: After median follow-up of 49 months, 21 patients had relapsed: 20 in PORT; and one in surgery alone group. As the first site of failure, distant metastasis was the most common (17 patients). Local recurrence occurred in three, and regional relapse in one. The lung was the most common site (10 patients), followed by the bone, and the brain. Five-yr disease free survival (DFS), local control, and overall survival (OS) rates were 74.4% and 94.7%, 96.0% and 100%, and 78.2% and 100% in PORT and surgery alone groups, respectively. On multivariate analysis, DFS was significantly affected by pN+ (hazard ratio [HR], 3.624; P=0.0319), while OS was by pN+ (HR, 7.138; P=0.0034) and perineural invasion (HR, 5.073; P=0.0187). CONCLUSION: Based on our experience, the patients with early stage major salivary gland cancer with low risk can be effectively treated by surgery alone, and those who with risk factors can achieve excellent local and regional control by adding PORT. Omitting elective neck irradiation in patients with N0 disease seems a feasible strategy under accurate clinical evaluation. An effort is needed to decrease distant metastasis through further clinical trials.

Result of Neoadjuvant Chemotherapy, Surgery and Radiation Therapy in Locally Advanced Breast Cancer / 대한방사선종양학회지

PURPOSE: To evaluate the result of neoadjuvant chemotherapy, surgery, and radiation therapy in locally advanced breast cancer as well as analyze the prognostic factors affecting survival. MATERIALS AND METHODS: One hundred fifty-nine patients with breast cancer were treated by neoadjuvant chemotherapy between April 1995 and November 2006 at the Samsung Medical Center. Among these patients, we retrospectively reviewed 105 patients treated with neoadjuvant chemotherapy followed by surgery and radiation therapy for a cure with an initial tumor size >5 cm or clinically positive lymph nodes. All patients received anthracycline based chemotherapy except for 2 patients. According to clinical tumor stage, 3 patients (3%) were cT1, 26 (25%) were cT2, 39 (37%) were T3 and 37 (35%) were T4. Initially, 98 patients (93%) showed axillary lymph node metastasis. The follow-up periods ranged from 7~142 months (median, 41 months) after the beginning of neoadjuvant chemotherapy. RESULTS: Locoregional failure free survival rate and distant metastasis free survival rate at 5 years were 82.1% and 69.9%, respectively. Disease free survival rate and overall survival rate at 5 years were 66.1% and 77.1%, respectively. The results of a univariate analysis indicate that clinical tumor stage, pathologic tumor stage, pathologic nodal stage and pathologic TNM stage were statistically significant factors for disease free survival rate and overall survival rate. Whereas, a multivariate analysis indicated that only hormone therapy was a statistically significant factor for survival. CONCLUSION: The current study results were comparable to other published studies for neoadjuvant chemotherapy for breast cancer. Hormone therapy was a statistically significant prognostic factor. The patients with early clinical or pathologic stage had a tendency to improve their survival rate.

The Effect of Cyclooxygenase-2 Expression on Tumor Volume Response in Patients Treated with Radiotherapy for Uterine Cervical Cancer

We investigated the correlation between Cyclooxygenase-2 (COX-2) expression and the tumor response in patients with cervical cancer that were treated with curative radiotherapy (RT). Fifty-seven patients with squamous cell carcinoma were treated with concurrent radiochemotherapy (CRCT, n=29) or RT alone (n=28). The response of each patient was evaluated by three serial Magnetic Resonance Imaging examinations: before the start of RT, at four weeks after the start of RT (mid-RT) and at four weeks after the completion of RT (post-RT). Forty-three patients had positive COX-2 expression. The COX-2 negative patients achieved a higher rate of complete response (CR) at mid-RT than did the COX-2 positive patients (28.6% vs. 7.0%, P=0.054), but not at post-RT (64.3% vs. 69.8%). The initial tumor volume was a significant predictor of CR at mid-RT (P=0.003) and post-RT (P=0.004). The multivariate analysis showed that the initial tumor volume (at mid-RT and post-RT) and CRCT (at post-RT) were significant predictors of CR; however, the COX-2 expression was not. In conclusion, the COX-2 expression status has no significant correlation with the tumor response. Further studies on the changes in COX-2 expression levels during RT may be helpful for determination of its role in the tumor response to treatment and patient prognosis.

Evaluation of Xerostomia Following 3 Dimensional Conformal Radiotherapy for Nasopharyngeal Cancer Patients / 대한방사선종양학회지

PURPOSE: This study is to evaluate the xerostomia following 3-dimensional conformal radiation therapy (3D CRT) in nasopharynx cancer patients using the xerostomia questionnaire score (XQS). MATERIALS AND METHODS: Questionnaire study was done on 51 patients with nasopharynx cancer who received 3D CRT from Dec. 2000 to Aug. 2005. 3D CRT technique is based on "serial shrinking field" concept by 3 times of computed tomography (CT) simulation. Total target dose to the primary tumor was 72 Gy with 1.8 Gy daily fractions. Xerostomia was assessed with 4-questions XQS, and the associations between XQS and time elapsed after RT, age, sex, stage, concurrent chemotherapy, and parotid dose were analyzed. RESULTS: Concurrent chemotherapy was given to 40 patients and RT alone was given to 11 patients. The median time elapsed after 3D CRT was 20 (1~58) months and the mean XQS of all 51 patients was 8.4+/-1.9 (6~14). XQS continuously and significantly decreased over time after 3D CRT (x(2)=-0.484, p or=35 Gy was significantly higher than or=35 Gy were suggested to adversely affect radiation-induced xerostomia.

The Results of Postoperative Radiotherapy for Early Stage Endometrial Carcinoma / 대한방사선종양학회지

PURPOSE: To determine treatment policy for early stage endometrial carcinoma, we analyzed the results of postoperative radiotherapy. MATERIALS AND METHODS: From Oct. 1994 to Aug. 2002, 42 patients with FIGO stage I endometrial carcinoma received postoperative radiotherapy. All patients received curative surgery and pelvic lymph node dissection was done in 26 patients. Based on the FIGO staging system, 3 were at stage IA, 21 were at stage IB and 18 were at stage IC. Histologically, there were 14 grade 1, 16 grade 2, and 12 grade 3. Nineteen patients received intracavitary brachytherapy and 23 patients did whole pelvic radiotherapy. The median period of follow-up was 41 months (22 to 100 months). RESULTS: Five-year overall survival, disease-free survival, local control, and regional control rates of all patients were 86.0%, 87.9%, 100%, and 97.5%, respectively. All failures were distant metastases in 5 patients and two patients had simultaneous regional recurrences. There was no intrapelvic failure in patients who received intracavitary radiotherapy. Grade 3 chronic complications were found in 1 patient (4.3%), who received whole pelvic radiotherapy. CONCLUSION: We achieved high rates of loco-regional control and survival by curative surgery and postoperative radiotherapy. However, we need to select the type of radiotherapy based on the risk factors for recurrence to reduce the treatment-related complication.