Particle therapy for mucosal melanoma of the head and neck. A single-institution retrospective comparison of proton and carbon ion therapy.

PURPOSE: To retrospectively analyze treatment outcomes after particle therapy using protons or carbon ions for mucosal melanoma of the head and neck (HNMM) at the Hyogo Ion Beam Medical Center, as well as to compare proton therapy (PT) and carbon ion therapy (CIT). PATIENTS AND METHODS: Data from 62 HNMM patients without metastasis, treated with PT or CIT between October 2003 and April 2011 were analyzed. Median patient age was 70.5 years (range 33-89 years). Of the total patients, 33 (53 %) had received PT and 29 (47 %) had undergone CIT. Protocols for 65 or 70.2 GyE in 26 fractions were used for both ion types. RESULTS: Median follow-up was 18.0 months (range 5.2-82.7 months). The 1-/2-year overall survival (OS) and local control (LC) rates were 93 %/61 % and 93 %/78 % for all patients, 91 %/44 % and 92 %/71 % for the PT patients and 96 %/62 % and 95 %/59 % for the CIT patients, respectively. No significant differences were observed between PT and CIT. Local recurrence was observed in 8 patients (PT: 5, CIT: 3) and 29 (PT: 18, CIT: 11) experienced distant metastases. Acute reactions were acceptable and all patients completed the planned radiotherapy. Regarding late toxicity, grade 3 or greater events were observed in 5 patients (PT: 3, CIT: 2), but no significant difference was observed between PT and CIT. CONCLUSION: Our single-institution retrospective analysis demonstrated that particle therapy for HNMM achieved good LC, but OS was unsatisfactory. There were no significant differences between PT and CIT in terms of either efficacy or toxicity.

External irradiation and intraluminal irradiation using middle-dose-rate iridium in patients with roentgenographically occult lung cancer.

PURPOSE: Therapeutic results were analyzed in 39 patients with roentgenographically occult lung cancer (ROLC), and the significance and optimal dose of this therapy were evaluated. METHODS AND MATERIALS: The subjects were 39 patients who underwent intraluminal irradiation between May 1987 and August 1999. Radiotherapy was performed by combining external irradiation with intraluminal irradiation using middle-dose-rate iridium (four 370-MBq wires) through a catheter with a spacer, which held the source in the center of the bronchus. The doses of radiation were 22-66 Gy (median value 45 Gy) by external irradiation and 10-46 Gy (median value 28 Gy) by intraluminal irradiation. RESULTS: The therapeutic effect was CR in 38 patients and PR in 1, and local recurrence was observed in a PR case and 3 of the 38 patients who showed CR. The 3-year and 5-year relapse-free survival rates were both 87%. No severe radiation injury was observed. CONCLUSIONS: Considering that ROLC often occurs as multiple cancers and that many patients with ROLC have reduced lung function, radiation therapy by a combination of intraluminal irradiation and external irradiation is expected to replace surgery as the first choice for the treatment of this disease in the twenty-first century.

Aichi Cancer Center 10-year experience with conservative breast treatment of early breast cancer: retrospective analysis regarding failure patterns and factors influencing local control.

PURPOSE: We analyzed the clinical results of conservative breast therapy in our institute to determine the risk factors influencing local and distant disease recurrence. METHODS AND MATERIALS: From 1989 to 1997, 301 breasts of 295 women with early breast cancer were treated with conservative surgery and adjuvant radiotherapy. There were 212 incidences of Stage I breast cancer, and 89 of Stage II. Patients were routinely treated with local resection, axillar dissection, and 46--50 Gy irradiation given in 23--25 fractions. Some also received a radiation boost to the tumor bed. RESULTS: The 5-/8-year overall survival, disease-free survival, and local control rates were 93.2/91.5%, 86.0/80.6%, and 95.1/92.5%, respectively. Using both univariate and multivariate analyses, tumor volume, estrogen receptor status, and age < 40 years were significant prognostic factors for disease-free survival. Both age < 40 years and surgical method had a strong effect on local control by uni- and multivariate analysis. Surgical margin status was a significant prognostic factor for local control at the univariate level (p < 0.0001), though it had only borderline significance at the multivariate level (p = 0.08). No patient experienced severe morbidity due to radiotherapy. CONCLUSION: The results obtained are comparable to previously reported data. Although the follow-up period was too short to draw definite conclusions about long-term outcomes, the outcome from conservative breast treatment was acceptable.

The treatment results of 40 patients with localized endobronchial cancer with external beam irradiation and intraluminal irradiation using low dose rate (192)Ir thin wires with a new catheter.

BACKGROUND AND PURPOSE: While bronchial intraluminal irradiation is valued highly as a useful palliative treatment for lung cancer, its role as a curative treatment is unclear. The treatment results of 40 localized enbobronchial tumors (including tracheal cancer) who underwent external beam irradiation (EBR) and intraluminal irradiation (IR) as a curative treatment is reported, and the role of combined EBR and IR as a curative potential treatment is examined. MATERIALS AND METHODS: Forty patients, including 22 with roentgenographically occult lung cancer (ROLC), 14 (18 lesions) with postoperative recurrent lung cancer (PORLC) and four with tracheal cancer, who underwent EBR and IR from February 1987 to August 1996, were studied. IR was conducted using low dose rate (1.48 GBq) (192)Ir thin wires at a bronchial mucosal dose of 4-6 Gy per fraction, with a total dose of 10-57 Gy (median 28 Gy). All patients were also given combined external Linac X-ray irradiation for a total dose of 30-77 Gy (median 52 Gy). RESULTS: As for the primary effect, complete response (CR) was obtained in all 22 ROLC cases; CR was obtained in 12 (16 lesions), partial response (PR) in one and minor response (MR) in one of the PORLC cases; and CR was obtained in three and PR in one of the tracheal cancer cases. The 3-year and 5-year local control rate by Kaplan-Meier method was 75 and 65%, respectively. Twenty-two patients survived for 3 years or longer. Complications included one case each of fatal tracheal hemorrhage, bronchial mucosal ulcer and bronchial stenosis. CONCLUSIONS: Combined EBR and IR is useful as a curative potential treatment, and long-term survival can be expected in ROLC, tracheal cancer and a portion of PORLC cases.

Radical radiotherapy for medically inoperable non-small cell lung cancer in clinical stage I: a retrospective analysis of 149 patients.

PURPOSE: In order to obtain the standard treatment results of medically inoperable non-small cell lung cancer (NSCLC) in Stage I in the post-CT scan era, a retrospective analysis of patients who were treated by radical radiotherapy was performed. METHODS AND MATERIALS: 149 cases treated between 1980 and 1989 were accumulated from ten large hospitals in Japan. All patients received a total dose of 55-75 Gy (mean 64.7 Gy) with conventional fractionation. For evaluation of treatment results, complete response (CR) rate, median survival period and long-termed survival rates were used. RESULTS: The median survival of the all cases was 27.2 months and the actuarial 3- and 5-year survival rates were 34.2% and 22.2%, respectively. CR was obtained in 57 cases (38%). The CR rate was strongly correlated with the long-term survival (5-year survival rate in CR group: 35.1% compared with PR + NC group: 14.1% (P < 0.0001)). The size of tumor was also of prognostic importance. In 116 patients who died within 5 years after treatment, 66 patients (57%) died of local tumor regrowth. CONCLUSION: Although the medically inoperable NSCLC patients in Stage I should be offered curative radiation therapy, development of some new steps to increase the CR rate and local control rate is urgently needed.

Alternating chemoradiotherapy for nasopharyngeal cancer using cisplatin and 5-fluorouracil: a preliminary report of phase II study.

Alternating chemoradiotherapy was performed in 35 patients with locally advanced nasopharyngeal cancer. The median duration of follow-up was 20 months, and the 2-year progression free and overall survival rates were 83% (95% confidence interval: 66~101%) and 94% (95% CI: 84~105%), respectively. This method may be useful in treating nasopharyngeal cancer.

Pancreatic ductal adenocarcinoma associated with Potter type III cystic disease.

Although polycystic liver disease (PLD) is known to be associated with autosomal dominant polycystic kidney disease, a finding of PLD with pancreatic ductal adenocarcinoma is extremely rare. We have experienced one such case of a ductal adenocarcinoma of the pancreas in a patient with Potter type III cystic disease of the liver and kidney. A 63-year-old man was admitted to our hospital because of obstructive jaundice. Six months previously, on admission to a local hospital for treatment of diabetes mellitus, he had been found to have polycystic disease of the liver and kidney. Ultrasound examination revealed dilatation of the intrahepatic bile duct and the common bile duct. Blood tests showed an elevated total bilirubin level. Abdominal computed tomography scans and magnetic resonance imaging demonstrated polycystic lesions in the liver and the bilateral kidneys. Percutaneous transhepatic cholangio-drainage was performed, and fluorography of the biliary tree revealed obstruction of the lower common bile duct, causing jaundice. This appears to be a case of independent association of pancreatic ductal adenocarcinoma with polycystic disease of the liver and kidney. The patient's sister, who also had polycystic disease of the liver and kidney, had died of squamous cell carcinoma of the tongue. Although familial associations of carcinomas with polycystic liver disease may be extremely rare, they provide a perspective for the etiology of polycystic liver disease.

Continuous selective intraarterial chemotherapy in combination with irradiation for locally advanced cancer of the tongue and tongue base.

We retrospectively evaluated the results of the concurrent combination therapy of selective continuous intraarterial chemotherapy and radiotherapy in 39 patients with locally advanced cancer of the tongue and tongue base between September 1992 and January 2000. Thirty patients were fresh cases (stage II, 10 patients; stage III, 15; stage IV, five) and nine were recurrent cases. The primary lesion was present in the mobile tongue in 33 patients and the tongue base in six. External irradiation (median dose, 48.6 Gy) was performed in all patients, and interstitial brachytherapy using an Au grain or Cs needle (median dose, 50 Gy) in 21. In intraarterial chemotherapy, a catheter was selectively inserted into the lingual artery via the superficial temporal artery, and carboplatin (CBDCA) was continuously infused (median dose, 460 mg/m(2)) concurrently with radiotherapy. In 13 patients with cervical lymph node metastasis, two courses of systemic chemotherapy with 5-FU (700 mg/m(2) x 5 days) and cisplatin (40-50 mg/m(2)x2 days) or its analog was also performed. In 37 (94.9%) of the 39 patients in whom this combination therapy was completed, the response rate was 94.6%. The 3-year local control rate, progression-free survival rate, and overall survival rate by Kaplan-Meier's method were 79.2, 53.2, and 58.9%, respectively. This combination therapy was effective for locally advanced cancer of the tongue and tongue base without causing severe adverse side effects, and a local control rate comparable to that by surgery can be expected.

New superselective intra-arterial infusion via superficial temporal artery for cancer of the tongue and tumour tissue platinum concentration after carboplatin (CBDCA) infusion.

We developed a new technique of superselective intra-arterial chemotherapy for tongue cancer using a modified (1.35 mm) angiographic catheter. The catheter was confirmed to be inserted into the lingual artery by the new technique. We measured the platinum concentrations in resected tumour tissues after infusion of carboplatin (CBDCA) at 20 mg/m2 over 30 min from 30 min before tumour resection in 12 patients with cancer of the tongue (6 patients: superselective intra-arterial infusion; 6 patients: conventional intra-arterial infusion). The mean platinum concentration in tumour tissue was 10.5 +/- 1.2 micrograms/g wet, which was more than twice higher than, and significantly different from, 4.3 +/- 3.8 micrograms/g wet by the conventional intra-arterial infusion method. This new superselective intra-arterial infusion method allows direct infusion of the anticancer agent into the artery supplying the tumour and is expected to become a new therapeutic modality for cancer of the tongue.

Patterns of failure in carcinoma of the uterine cervix treated with definitive radiotherapy alone.

The purpose of this retrospective study was to evaluate the patterns of failure for the patients treated with definitive radiotherapy, and to discuss future treatment strategies for the uterine cervical cancer. From 1986 to 1995, 177 patients with stages I-III cervical cancer treated with a combination of two-axial conformal radiotherapy and radium brachytherapy were analyzed. The first treatment failures were pelvic failure in 11%, and distant metastases (DM) in 16% of the 177 patients. Paraaortic lymph nodes (PAN) were the most frequently metastatic regions (71%). In the pelvic control group, DM were in 6% of patients for stages I-II, and in 32% of patients for stage III. In the pelvic failure group, DM were in 75% of patients for stages I-II, and in 19% of patients for stage III. In stages I-II, the DM rate was significantly correlated with pelvic tumor control. However, there was no correlation in stage III. To improve survival, it is important to increase the pelvic tumor control rate for patients with stage I-II, and to increase the pelvic tumor and metastatic control rate in stage III. Additional treatments such as chemotherapy and/or PAN irradiation using conformal radiotherapy are required in stages I-II with locally bulky tumor and in stage III.

Therapeutic effects of simultaneous intraluminal irradiation and intraluminal hyperthermia on oesophageal carcinoma.

An applicator enabling simultaneous intraluminal radiotherapy and intraluminal hyperthermia delivery was developed to improve the treatment results for locally advanced oesophageal carcinoma. Eight inoperable cases were treated by this method. Six cases received 40 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (3 Gy and 4 Gy in three cases each) once weekly for 3 weeks; the remaining two cases received 50 Gy external irradiation followed by simultaneous intraluminal hyperthermia and radiotherapy (4 Gy) once weekly for 2 weeks. Hyperthermia was delivered by a radiofrequency current thermotherapy instrument for 30 min at an output that raised the oesophageal mucosal surface temperature to 42-43 degrees C. Intraluminal radiotherapy was delivered with a microSelectron to a submucosal depth of 5 mm after the first 15 min of hyperthermia. Four cases achieved complete response, with all demonstrating local control. Partial response was obtained in four cases, and three of these patients died of local recurrence. There were no significant adverse side effects apart from fistula in one case. In conclusion, simultaneous intraluminal radiotherapy and hyperthermia may improve the current treatment results for locally advanced oesophageal carcinoma.

Severe obstruction of the superior vena cava caused by tumor invasion. Recanalization using a PTFE-covered Z stent.

Bare stents are commonly used for the treatment of malignant vena cava stenoses. However, the therapeutic effect of treatment using bare stents for cases with intraluminal tumor invasion is not satisfactory. We report a case with severe obstruction of the superior vena cava caused by tumor invasion of mediastinal lymph node metastases from colon cancer, which was successfully treated by the recanalization of superior vena cava using a polytetrafluoroethylene-covered Z stent. The covered stent could not be fully expanded at first, and re-obstruction developed at the stented site due to thrombus formation soon after stenting. So, the additional balloon dilatation made the stent expend fully on another day of stenting. After the balloon dilatation blood flow improved immediately and the clinical symptoms associated with the superior vena cava obstruction resolved. Thereafter no symptomatic recurrence has been observed in 12 months of follow-up period.

A case of esophageal carcinoma surgically treated after discontinuance of the simultaneous application of radiotherapy and chemotherapy with low doses of CDDP and 5-FU.

The patient, a 69-year-old man with esophageal cancer, had a type 2 tumor in the Mt region, accompanied with an ulcer measuring 12 cm in the major axis. In addition, lymph node metastasis, approximately 5x4 cm, was observed in the lesser curvature of the stomach. The clinical stage of the lesion was T3N1M0 (stage III), and simultaneous therapy combining radiotherapy (2 Gy/day) with chemotherapy employing CDDP (6 mg/day) and 5-FU (300 mg/day) was started on October 21, 1996. During treatment, tumor invasion into the gastric walls from lymph node metastasis was observed on endoscopy, and radiotherapy was discontinued at a total dose of 40 Gy to avoid the possibility of bleeding. Surgery was performed on January 8, 1997. Although tumor invasion from lymph node metastasis in the lesser curvature of the stomach was observed in the pancreas, no remaining cancer cells were noted in the primary nest and metastasized lymph node, suggesting the usefulness of the simultaneous combined therapy.

Outcomes of radiotherapy for inoperable locally advanced (T4) esophageal cancer-retrospective analysis-.

To assess the treatment outcome after radiotherapy with or without chemotherapy for inoperable locally advanced (T4) esophageal cancer (EC), a retrospective analysis was performed. We enrolled 37 patients with T4 EC and analyzed 35 patients. A total of 28 patients were treated with radiotherapy and chemotherapy (median dose, 60 Gy) and seven patients were treated with radiation alone (median dose, 60 Gy). Many mainly received high-dose cisplatin (CDDP) and 5-fluorouracil (FU) or continuous infusion of low-dose CDDP and 5-FU. Among the 35 patients, there were eight survivors and 27 deaths. The median follow-up period was 15.5 months (3.5 to 74 months). The one-year, 3-year, and 5-year survival rates were 37.5%, 10.0%, and 10.0%, respectively, with a median survival time (MST) of 7.3 months. When the patients were divided into two groups, a complete response (CR) group and a non-CR group, MST was 16.5 and 6.2 months, respectively, showing significant differences between the two groups (p=0.0317). CR patients showed more satisfactory long-term outcomes than non-CR patients.

Treatment results of chemoradiation for T1 esophageal cancer with lymph node metastases.

PURPOSE: We clinically evaluated 12 patients with advanced superficial esophageal cancer who had undergone chemoradiotherapy. PATIENTS AND METHODS: A retrospective analysis was performed between October 1992 and December 1998 on 12 patients with M1 metastasis in lymph nodes or direct invasion of enlarged lymph nodes (A3) to adjacent structures. Combined treatment with radiotherapy and chemotherapy was applied to all patients. High-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) were administered to five patients, low-dose CDDP and 5-FU to five patients, and others to two patients. Ten patients were treated by external irradiation alone, and two patients were treated by external and intracavitary irradiation. RESULTS: Of the 12 patients, the response of the primary tumor to this therapy resulted in 11 CRs (91.6%) and one PR, while the response of the largest metastatic lesion in lymph nodes in each patient resulted in three CRs (25%), four PRs (33.3%), and five NCs (41.6%). The 2-year survival rate of all patients was 51.9%, and MST was 28.9 months. The 2-year survival rates of the M1 and A3 patients were 60.0% and 41.7%, respectively. CONCLUSION: This study revealed that the present chemotherapy regimen is ineffective in treating metastatic lymph node lesions. Therefore, it will be necessary to evaluate the effectiveness of chemoradiotherapeutic agents from the perspective of their effects on metastatic lymph nodes.

[Alternating chemoradiotherapy for oropharyngeal cancer].

To evaluate the usefulness of chemoradiotherapy for oropharyngeal cancer, we retrospectively analyzed disease-free survival (DFS) and acute toxicities of the patients treated with this therapy. Between 1990 and 1998, 15 patients were treated with alternating chemoradiotherapy (CRT). Chemotherapy (CT) mainly consisted of 5-fluorouracil 700 mg/m2 (i.v.) on days 1-5 and nedaplatin 100-140 mg/m2 (i.v.) on day 6. Chemotherapy was administered before the beginning of radiotherapy. One cycle of this treatment consisted of CT and a subsequent 27 to 36 Gy of radiotherapy, as a general rule, two cycles were performed. Radiotherapy was delivered in single daily fractions of 1.8 to 2 Gy, to a total dose of 54 to 75 Gy for local lesions and 45 to 86.3 Gy for nodal metastases in the neck. As a historical control, 52 patients treated with curative radiotherapy between 1971 and 1990 were analyzed and compared with the CRT group in terms of DFS. The complete response rate with CRT was 100%. The three-year DFS were 87% and 38% with CRT and RT, respectively. There was a significant difference between the two groups (p = 0.0081). The most frequent and severe acute toxicity was mucositis, with grade 3-4 occurring in 47%. Acute hematologic toxicities were mild. Therefore, this CRT is considered to be an effective and tolerable treatment, and is expected to improve survival for oropharyngeal cancer patients.

[Two cases of squamous cell carcinoma of the anal canal treated with chemoradiotherapy].

We recently treated 2 patients with squamous cell carcinoma in the anal canal with bilateral inguinal nodal metastases using chemoradiotherapy. Chemotherapy (CT) consisted of 5-fluorouracil 700 mg/m2/day (continuous intravenously) on days 1-5 and cisplatin 50 mg/m2/day (continuous intravenously) on days 6-7. Chemotherapy was administered before the beginning of radiotherapy. In one patient, 2 cycles of CT were performed, and in the other patient 1 cycle only. The total radiation dose was 57.6 Gy to the primary lesion in each patient, and 53.6 Gy, 55.8 Gy to the nodal metastases, respectively. As a primary treatment response, CR was obtained in both patients. Acute grade 3-4 hematologic toxicities were observed in one patient. The patients have had 7 and 9 months survival without disease, and excellent function of the anal sphincter after treatment.

Particle therapy using carbon ions or protons as a definitive therapy for patients with primary sacral chordoma.

OBJECTIVE: This study retrospectively evaluated the efficacy and toxicity of particle therapy using carbon ions or protons for primary sacral chordomas. METHODS: We evaluated 23 patients with primary sacral chordoma treated with carbon ion therapy (CIT) or proton therapy (PT) between July 2005 and June 2011 at the Hyogo Ion Beam Medical Center, Hyogo, Japan. The median patient age was 72 years. 14 patients were treated with 70.4 Gy equivalents (GyE) in 16 fractions and 9 were treated with 70.4 GyE in 32 fractions. CIT was used for 16 patients, and PT was used for 7 patients. RESULTS: The median follow-up period was 38 months. At 3 years, local control (LC), overall survival (OS) and progression-free survival (PFS) for all patients were 94%, 83% and 68%, respectively. The log-rank test revealed that male sex was significantly related to better PFS (p=0.029). No other factors, including dose fractionation and ion type, were significant for LC, OS or PFS. In nine patients, ≥ Grade 3 acute dermatitis was observed, and ≥ Grade 3 late toxicities were observed in nine patients. The 32-fraction protocol reduced severe toxicities in both the acute and late phases compared with the 16-fraction protocol. CONCLUSION: Particle therapy for patients with sacral chordoma showed favourable LC and OS. Severe toxicities were successfully reduced by modifying the dose fractionation and treatment planning in the later treatment era. Thus, this therapeutic modality should be considered useful and safe. ADVANCES IN KNOWLEDGE: This is the first study including both CIT and PT for sacral chordomas.

Factors associated with nodal metastasis in nasopharyngeal cancer: an approach to reduce the radiation field in selected patients.

OBJECTIVES: The purpose of this study was to investigate factors associated with lymph node (LN) metastasis to identify which nasopharyngeal cancer (NPC) patients can undergo a reduction in the prophylactic radiation field. MRI of biopsy-proven NPC patients was evaluated to determine primary tumour extension and the existence of LN metastasis. METHODS: Sex, age, pathological type, T stage, primary tumour size, existence beyond the midline of the nasopharynx at the primary site and parapharyngeal extension of the primary tumour were assessed regarding their impact on the laterality of LN metastasis using the χ(2) test. RESULTS: Of the 167 patients, 149 (89%) showed nodal involvement. The existence beyond the midline of the nasopharynx was significantly associated with the laterality of LN metastasis (p<0.0001). Most patients (82%) with primary tumour presence within the midline showed only ipsilateral LN metastasis or no LN metastasis. In addition, contralateral LN metastases were seen only at Level II and the retropharyngeal LN among most of other patients. CONCLUSION: These results suggest that LN areas other than Level II and the retropharyngeal LN on the contralateral side could be omitted in patients with primary tumour presence within the midline and without the contralateral Level II or the retropharyngeal LN. Whether disease control is compromised by reducing the radiation field for subclinical diseases is a problem that should be solved in the future by prospective study.