Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II-III breast cancer? A multicentre retrospective study (KROG 12-05).

BACKGROUND: To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II-III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT). METHODS: We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated. RESULTS: After a median follow-up period of 66.2 months (range, 15.6-127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0-is vs 1 vs 2-4) and the number of LNs sampled (<13 vs ≥13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled. CONCLUSIONS: ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.

Stereotactic body radiotherapy with helical tomotherapy for pain palliation in spine metastasis.

To evaluate the pain response, local tumor control and toxicity of stereotactic body radiotherapy (SBRT) with helical tomotherapy (HT) in the patients with spine metastasis. From May 2009 to June 2010, 22 patients with 31 lesions were treated by SBRT. Dose scheme were 24 Gy in 3 fractions (87.1%), 30 Gy in 5 fractions (9.7%), and 16 Gy in a single fraction (3.2%). Pain was assessed using a numerical rating scale. Analgesic consumption was recalculated into the daily oral morphine-equivalent dose (OMED). The response criteria of International Bone Metastases Consensus Group (IBMCG) was used. The median follow-up duration was 10 months (range 3-23 months). After SBRT the mean pain score decreased significantly (4.32 before SBRT, 0.71 at 3 months). However, median OMED didn't decrease until 3 months after SBRT (Median OMED; 34.5 mg before SBRT, 45 mg at 3 months). Pain response rate and pain progression-free survival rate at 3 month was 96.8 and 93.5%, respectively. Local progression-free survival rate at 3 month was 93.5%. There was no severe acute toxicity. SBRT with HT is a safe and effective treatment modality for local tumor control and pain palliation associated with spine metastasis.

Primary squamous cell carcinoma of the parotid gland.

PURPOSE: To investigate the clinical behavior and treatment outcome of patients with primary squamous cell carcinoma (SCC) of the parotid gland. PATIENTS AND METHODS: Twelve cases of primary SCC originating in the parotid gland were retrospectively reviewed. The majority of patients had a locally advanced disease. Eight cases underwent a combination of radical surgery and postoperative radiotherapy, whereas the remaining four cases were treated with radiotherapy alone. Patterns of treatment failure, survival rate, and prognostic factors for these patients were investigated. RESULTS: The predominant pattern of failure was local failure, either alone or in combination with other failures. Two patients who were treated with radiation alone had persistent disease after completion of treatment, whereas 4 of 8 patients who received combined modality treatment and 2 of 4 patients who were treated with radiation alone subsequently developed local recurrences in the primary site or surgical bed. The local failure rate and regional failure rate were 58% and 25%, respectively. Most locoregional recurrences developed within 1 year after initial treatment. Only 2 patients had distant metastasis. The prognosis appeared to be relatively poor for those patients, compared with those with SCC in other head and neck sites. The overall 5-year actuarial survival rate and the disease-free survival rate were 31% and 33%, respectively. Although advanced stage, facial nerve palsy, and regional lymph node metastasis all portended an unfavorable prognosis, only patient age and treatment modality were found to be statistically significant poor prognostic factors. CONCLUSIONS: Primary SCC of the parotid gland is an uncommon tumor with a highly malignant potential. Our results indicate that a combination of radical surgery and postoperative radiotherapy is the treatment of choice for achieving better locoregional control rates and improved cure rates in the treatment of these patients.

A feasibility study using three-dimensional conformal boost technique in locally advanced carcinoma of the nasopharynx.

To investigate the feasibility and efficacy of dose escalation using three-dimensional (3-D) conformal boost technique, 21 patients with stage III or IV nasopharyngeal cancer were enrolled in a prospective protocol. All patients with node metastases initially received external radiotherapy by conventional technique up to 70.2 Gy, followed by 3-D conformal radiotherapy (3-D CRT) to the boost part up to 79.2 Gy with 9 Gy increments (daily fraction of 1.8 Gy for 5 days). A modified technique with the same dose escalation of 9 Gy using 3-D CRT was applied to 7 patients without node metastases, who were treated by conventional technique up to 54 Gy, followed by 3-D CRT to boost up to a basic dose of 70.2 Gy, and then finally with dose escalation of 9 Gy. The protocol was relatively well tolerated by the majority of patients. Acute complications during the dose escalation schedule was low, with rare occurrences of grade 3 or 4 toxicity. Although late radiation-induced complications also appeared limited, 1 patient developed a temporal lobe necrosis and 2 patients suffered from sensory-neural hearing loss. There were no radiation-induced fatal complications. At a median follow-up of 48 months, only 3 patients experienced local failure and 2 patients developed distant metastases. The 5-year overall actuarial survival rate and recurrence-free survival rate for all patients were 68% and 85%, respectively. On the basis of acceptable morbidity and encouraging treatment results, we conclude that the dose escalation in 9 Gy increments using a 3-D conformal boost technique is relatively safe and efficacious, enough to be used routinely for locally advanced nasopharyngeal cancers.

Hyperfractionated re-irradiation using a 3-dimensional conformal technique for locally recurrent carcinoma of the nasopharynx; preliminary results.

To evaluate the efficacy of hyperfractionated re-irradiation using a three-dimensional conformal radiotherapy (3-D CRT) technique in patients with locally recurrent carcinoma of the nasopharynx. Four patients with locally recurrent nasopharyngeal cancer were retreated with a hyperfractionated schedule using a 3-D CRT technique. Re-irradiation was delivered in 1.1-1.2 Gy fractions twice per day (BID), with interfraction intervals of more than 6 hours. The total dose ranged from 59.4 to 69.2 Gy. A 3-D CRT technique with 5- or 6-field coplanar and/or non-coplanar beams were employed during the entire treatment procedure. All four patients achieved complete remission of locally recurrent lesions, with marked improvement of subjective symptoms, immediately after re-irradiation. All are alive and well without evidence of disease after limited follow-up periods, which range from 7 to 20 months. So far, there have been no radiation-induced neurologic complications. Four patients with locally recurrent carcinoma of the nasopharynx were successfully treated by hyperfractionated re-irradiation using a 3-D CRT technique. A relatively high re-irradiation dose of more than 60 Gy may be safely delivered with no serious acute or late radiation-induced complications in patients with local recurrences and who were initially treated with doses greater than 70 Gy.

Neoadjuvant chemotherapy and radiation for inoperable carcinoma of the maxillary antrum: a matched-control study.

A matched-control study comparing standard radiotherapy versus neoadjuvant chemotherapy and radiation was undertaken to clarify the effects of neoadjuvant systemic chemotherapy for locally advanced squamous cell carcinoma of the maxillary antrum. Thirty-four patients with inoperable maxillary cancer were treated with neoadjuvant chemotherapy and radiotherapy (Group II). Before starting radiotherapy, all patients in Group II received two or three cycles of neoadjuvant chemotherapy consisting of cisplatin and a 5-day continuous infusion of 5-fluorouracil with or without intravenous injection of vinblastine. Radiation doses ranged from 66 Gy to 75 Gy (median, 70 Gy). The response rate, patterns of failure, toxicity, and survival for Group II were compared with those for 34 stage-matched patients treated with radiation alone (Group I). Despite a higher response rate to neoadjuvant chemotherapy, the recurrence rate and patterns of treatment failure were not influenced by the addition of neoadjuvant chemotherapy. In most cases, neoadjuvant chemotherapy did not interfere with subsequent radiotherapy, and radiation-induced late complications occurred equally in both treatment groups. After a median follow-up of 48 months, there was no significant difference in 5-year actuarial survival or disease-free survival between the two treatment groups. Radiation alone for inoperable maxillary cancer was clearly suboptimal for improving local control and survival rate, but neoadjuvant chemotherapy in addition to standard radiotherapy failed to demonstrate any therapeutic advantage over radiation alone.

Clinical significance of neck node metastasis in squamous cell carcinoma of the maxillary antrum.

PURPOSE: To further clarify the clinical significance of neck node metastasis in squamous cell carcinoma of the maxillary sinus (maxillary SCC). MATERIALS AND METHODS: The medical charts of the 116 patients with maxillary SCC were retrospectively reviewed. Twelve patients (10.3%) presented initially with neck node metastases, and 14 (13.5%) of 104 node-negative patients subsequently developed regional recurrence during the follow-up period. The high-risk factors for neck node metastasis, patterns of regional failure, and survival for node-positive patients were analyzed with the patient cohort that had largely been treated with radiation alone. RESULTS: Of the various factors, the tumor extension to the nasopharynx or oral cavity was the statistically significant determinants predictive of neck node metastasis at the initial diagnosis. During the follow-up period, regional failure was far less common than local failure (19.0% v 68.1%), and the majority of regional failures were accompanied by local recurrences. The oral cavity extension and control status of local disease were the high-risk factors for subsequent development of regional recurrence in node-negative patients. The overall 5-year survival rate for node-positive patients (16.7%) showed a poorer outcome compared with that for node-negative patients (31.3%), but it was similar to that of T4N0 patients (26.6%). Although patients who subsequently developed neck node recurrence during follow-up represented a dismal prognosis, uncontrolled local diseases in these patients still remained a major problem, resulting in a poor prognosis. CONCLUSIONS: Despite an unfavorable prognosis of patients with neck node metastasis, an aggressive trial to achieve maximum local control of the primary tumor was considered to be more important than elective neck treatments.

Role of definitive radiation therapy for larynx preservation in patients with advanced laryngeal cancer.

OBJECTIVE: Recently, neoadjuvant chemotherapy (CT) and radiation therapy (RT) have been advocated as a standard treatment for laryngeal preservation in patients with locally advanced laryngeal cancer. However, it is still being debated whether adding neoadjuvant CT to conventional RT makes an effective contribution to laryngeal preservation. The current study was designed to resolve this controversy. DESIGN: Retrospective clinical study. SETTING: The Severance Hospital, Yonsei Cancer Center, Yonsei University, Seoul, Korea. METHOD: Eighty patients (stages III, IV) with squamous cell carcinoma of the larynx were divided into two groups according to treatment modalities, which consisted of RT alone (N = 40, Group 1) and neoadjuvant CT plus RT (N = 40, Group 2). Comparative analysis was undertaken to investigate the differences in the organ preservation rate and treatment results between the two groups. RESULTS: There was no significant difference in the response rate and patterns of treatment failure between the two groups. The 5-year survival rate was similar between Group 1 (24%) and Group 2 (31%) (p = .1556). In addition, the larynx was almost equally preserved in Group 1 (62%) versus Group 2 (63%). CONCLUSIONS: Radiation therapy without neoadjuvant CT seems to be a valid alternative treatment for the purpose of laryngeal preservation in locally advanced laryngeal cancer.

Adenoid cystic carcinoma of the maxillary antrum.

PURPOSE: To investigate characteristic clinical features and outcome for patients with adenoid cystic carcinoma (ACC) of the maxillary antrum. PATIENTS AND METHODS: Twenty-two patients with ACC of the maxillary antrum were initially treated with surgery alone (3 patients), radiation alone (9 patients), or a combination of surgery and radiation (10 patients). Salvage treatment for initial failure was individualized. Patterns of failure, survival, and prognostic factors were retrospectively analyzed. RESULTS: The most frequent site of failure was local recurrence at the primary site (72.7%). All patients treated with either surgery alone or radiation alone experienced one or more local recurrences, whereas patients who received planned combined surgery and radiation had a much lower local recurrence rate (40%). Neck node failure (4.6%) was an uncommon event, whereas distant metastases were clinically documented in seven patients (32%). Most of the treatment failures appeared within 5 years, but treatment failures after 5 years were not uncommon. The overall survival and disease-free survival rates at 10 years were 37.6% and 13.6%, respectively. Clinicopathological factors, such as location of primary tumor, tumor stage, and histological grade were of no value in predicting a favorable survival. The significant prognostic factors influencing 10-year survival were the pathological finding of perineural invasion and the initial mode of treatment. CONCLUSION: ACC of the maxillary antrum represented a unique natural history characterized by a more aggressive tumor behavior and an unfavorable prognosis. Combined surgery and radiotherapy is recommended for optimal local control and survival.

Combined transcatheter arterial chemoembolization and local radiotherapy of unresectable hepatocellular carcinoma.

PURPOSE: The best prognosis in hepatocellular carcinoma (HCC) can be achieved with surgical resection; however, the number of resected cases are limited due to advanced lesions or associated liver disease. The purpose of this study was to investigate the efficacy and toxicity of a prospective trial of combined transcatheter arterial chemoembolization (TACE) and local radiotherapy (RT) in unresectable HCC. METHODS AND MATERIALS: Patients with histologically proven unresectable HCC due to either advanced lesions or associated cirrhosis were eligible. From March 1992 to August 1994, 30 patients were entered into this study. TACE was performed with Lipiodol (5 ml) and doxorubicin (Adriamycin ; 50 mg), followed by gelatin sponge particle (Gelfoam) embolization. Local RT was started within 7-10 days following TACE. Mean tumor dose was 44.0+/-9.3 Gy in daily 1.8 Gy fractions. Response was assessed by computerized tomography (CT) scan 4-6 weeks following completion of the treatment and then at 1-3-month intervals. Survival was calculated from the start of TACE using the Kaplan-Meier method. RESULTS: An objective response was observed in 19 patients, giving a response rate of 63.3%. Distant metastasis occurred in 10 patients, with 8 in the lung only and 2 in both lung and bone. Survival rates at 1, 2, and 3 years were 67%, 33.3%, and 22.2%, respectively. Median survival was 17 months. There were 6 patients surviving more than 3 years. Toxicity included transient elevation of liver function tests in all patients, fever in 20, thrombocytopenia in 4, and nausea and vomiting in 1. There was no treatment-related death. CONCLUSION: Combined TACE and local RT is feasible and tolerable. It gives a 63.3% response rate with median survival of 17 months. We feel that this regimen would be a new promising modality in unresectable HCC. Further study is required to compare the therapeutic efficacy of this regimen to TACE alone.