[A Case of Resection of Advanced Pancreatic Adenosquamous Carcinoma in which Multidisciplinary Treatment Was Effective].

A 72-year-old man with general fatigue was referred, and CT and MRI revealed a pancreatic mass with necrosis that was suspected of invading the stomach, splenic artery, celiac artery, liver, and portal vein. Upper gastrointestinal endoscopy showed an extrinsic mass with ulcer formation in the posterior wall of the upper gastric corpus and irregular mucosa in the lower esophagus incidentally. Biopsy showed squamous cell carcinoma from both lesions, leading to the diagnosis of pancreatic adenosquamous carcinoma and early esophageal cancer. We performed distal pancreatectomy with splenectomy, total gastrectomy, partial hepatectomy, superior mesenteric-portal vein resection, and reconstruction. The pathological results revealed pancreatic adenosquamous carcinoma and infiltration of cancer cells at the dissected peripancreatic margin. Therefore, we administered radiotherapy(50.4 Gy to the retroperitoneal region)in postoperative month 2. Endoscopic mucosal resection was performed for the early stage esophageal cancer lesion in postoperative month 5. Three courses of S-1 were administered as adjuvant therapy since postoperative month 7, and he is currently alive without recurrence 1 year and 8 months after surgery. Multidisciplinary treatment can be effective for locally advanced pancreatic adenosquamous carcinoma.

A Phase I Study of S-1 and Gemcitabine with Concurrent Radiotherapy in Patients with Non-Metastatic Advanced Pancreatic Cancer.

BACKGROUND/AIMS: To determine the recommended dose (RD) for full-dose S-1 and low-dose gemcitabine combined with radiotherapy in patients with non-metastatic advanced pancreatic cancer. METHODOLOGY: Adult patients with non-metastatic advanced pancreatic cancer (Union for International Cancer Control T stage 3 or 4) were eligible. The weekly intravenous gemcitabine (level 0-1: 200 mg/ml,level 2: 300 mg/m on Days 1, 8, 15, 22, 29, 36) dose was escalated starting from level 1 in a 3+3 design along with full dose twice-daily oral S-1 (level 0: 60 mg/m2/day, level 1-2: 80 mg/ml/day), and was administered on the same days as radiotherapy (1.8 Gy x 28 days). RESULTS: Eight patients were included in this study. A dose-limiting toxicity (DLT) (grade 4 neutropenia) was observed in one of the first three patients in level 1, and three additional patients received the level 1 dose without any severe adverse events. DLTs (grade 3/4 neutropenia) were then observed in the first two patients given level 2 dose. Therefore, level 1 was designated as the RD. Common grade 3/4 toxicities included neutropenia (62.5%), anorexia (37.5%), and pneumonitis (12.5%). CONCLUSIONS: The combination of S-1 and gemcitabine with concurrent radiotherapy is a feasible regimen at the level 1 dose.

Clinical outcome of adjuvant radiotherapy for squamous cell carcinoma of the breast; a multicenter retrospective cohort study.

BACKGROUND: Because primary squamous cell carcinoma (SCC) of the breast is a rare disease, the standard therapy has not been established. We examined the clinical outcomes of postoperative adjuvant radiotherapy for breast SCC. MATERIAL AND METHODS: We conducted a multicenter retrospective cohort study. Patients diagnosed with primary breast SCC who received adjuvant radiotherapy as part of their primary definitive treatment were included. Overall survival (OS), breast cancer-specific survival (BCSS), and recurrence-free interval (RFi) were evaluated. RESULTS: Between January 2002 and December 2017, 25 breast SCC patients received adjuvant radiotherapy as a primary treatment were included. Median follow-up time was 43.5 months. Three (12%), fifteen (60%) and seven (28%) patients had clinical stage I, II and III disease, respectively. Fourteen patients underwent breast-conserving surgery and subsequent adjuvant radiotherapy. Eleven patients underwent mastectomy and post-mastectomy radiotherapy. Ten patients received regional lymph node irradiation. Nine (36%) patients had disease recurrence. The first site of recurrence was locoregional in five, but distant metastasis arose in one. Concurrent local and distant metastasis were seen in two. Six cases of local recurrence occurred within the irradiated site. Seven patients died, and six of the deaths were due to breast cancer. Five-year OS, BCSS, and Rfi were 69%, 70%, and 63%, respectively. In multivariate analysis, age and lymphatic invasion were associated with increased risk of recurrence. CONCLUSION: Breast SCC has a high incidence of locoregional recurrence and poor prognosis. Age and lymphatic invasion are significant risk factors for recurrence.

Assessment of SPECT-CT fusion images and semi-quantitative evaluation using SUV in 123I-IMP SPECT in patients with choroidal melanoma.

OBJECTIVES: The aim of this study was to assess the diagnostic ability of N-isopropyl-p-[I-123] iodoamphetamine (IMP) SPECT semi-quantitative evaluation based on the standardized uptake value (SUV) in patients with choroidal melanoma. The secondary aim was to investigate the 6-h IMP SPECT imaging in comparison with 24-h imaging. METHODS: Twenty-five patients (14 males and 11 females, mean age of 59.2-year-old) were analyzed in this retrospective study. Patients underwent 24-h IMP SPECT imaging with a gamma camera after intravenous injection of IMP. Twelve of 25 patients underwent 6-h SPECT imaging in addition to the 24-h imaging. All acquired SPECT images were fused with CT images using an image-analysis software. To assess the utility of semi-quantitative evaluation method, we introduced an image evaluation method using SUVmax comparing with conventional count-based uptake index (UI) evaluation of the lesion. Volumes-of-interest (VOIs) for SUVmax and regions-of-interest (ROIs) for UI were drawn referring to the SPECT-CT fusion image. Then the relationship between the 6- and 24-h images was examined both in SUV and UI evaluation. Furthermore, the relationship between the size category classification (SCC) by UICC/AJCC: 1-4 scales and each semi-quantitative value using SUVmax and UI was also assessed. RESULTS: SUVmax of the tumor was significantly higher than that of the normal side; 2.37 ± 0.88 and 1.77 ± 0.39 (P < 0.05) on 6-h image, 4.17 ± 1.73 and 2.04 ± 0.45 (P < 0.001) on 24-h image, respectively. UI of the tumor was also significantly higher than that of the normal side; 2.24 ± 0.67 and 1.53 ± 0.35 (P < 0.01) on 6-h image, 3.79 ± 1.24 and 1.67 ± 0.44 (P < 0.001) on 24-h image, respectively. There was a strong significant linear relationship in the evaluation with SUVmax between 6- and 24-h on the tumor side (R2 = 0.88, P < 0.0001), compared to that with Tumor-UI (R2 = 0.35, P < 0.05). In addition, SUVmax of the tumor clearly differentiated the SCC of the tumor category 4 from that of category 1, where SUVmax of the tumor for categories 1‒4 were 2.56 ± 0.59, 4.33 ± 1.92, 4.63 ± 1.45, and 5.73 ± 1.69, respectively (P < 0.05, for categories 1 and 4). CONCLUSIONS: The semi-quantitative evaluation by SUV of 123I-IMP SPECT images fused with CT images is useful for detecting choroidal melanoma. Moreover, 6-h imaging with SUV-based evaluation of 123I-IMP SPECT is promising compared to the conventional count-based UI evaluation method. Trial registration This study is registered in UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000038174.

[Hyperfractionated radiation therapy for head and neck cancers].

Among various altered fractionation regimens, hyperfractionated radiotherapy (HFRT) has been considered effective to raise survival rate(SR)as well as local control rate(LCR)in head and neck cancers. We reviewed our results of HFRT (117 cases) treated between 1995 and 2004 and compared with those of conventionally fractionated radiotherapy (CFRT; 80 cases) treated during the same period. By disease site, naso-/oro-/hypopharynx/larynx were 5/23/44/45 vs. 10/6/10/54. There were more advanced-stage cases in HFRT group (stage I/II/III/IV = 19/36/23/35 vs. 42/16/8/ 14). Median RT dose were 72 Gy vs. 66 Gy. In 71 cases, chemotherapy was added (HF/CF = 54/17). In stage III and IV cases, there was a borderline significant difference in LCR (at 5 years; 44.3% for HFRT group vs. 24.5% for CFRT group; p = 0.0502), and a tendency in SR(at 5 years; 50.7% for HFRT group vs. 16.7% for CFRT group; p = 0.1210). By disease site, LCR of HFRT group was higher in hypopharynx(p = 0.0005)and oropharynx(p = 0.0003), and SR of HFRT group was higher in hypopharynx(p = 0.0023). Acute toxicity was heavy but in most cases it was tolerable and there were no severe late toxicities. From our data, it was suggested that HFRT might be effective in certain kinds of head and neck cancers.

Therapeutic results for 100 patients with cancer of the mobile tongue treated with low dose rate interstitial irradiation.

AIM: To evaluate the conservativeness of low dose rate interstitial irradiation (LII) for cancer of the mobile tongue. PATIENTS AND METHODS: Between 1975 and 2002, 100 consecutive patients (71 men, 29 women) underwent LII as curative treatment. Stages were I/IIIII/IV = 16/63/16/4. Seventy-one cases were treated with LII alone and 29 cases treated combined with external irradiation. Median total dose of LH was 70 Gy/7 days. RESULTS: Overall, 5- and 10-year local control and LII-treated patients' survival rates were 93% and 91%, 64% and 57%, respectively. Delayed neck metastases were observed in 21% of initially N0 cases, 56% of which could be salvaged by operation. Early stage and well-differentiated tumors carried better prognoses. CONCLUSION: LII of cancers of the mobile tongue results in good local control and survival. With careful monitoring of patients to ensure early detection of delayed metastases, LII should allow organ conservation and yield favourable therapeutic results compared with those of surgery.

Stereotactic irradiation for intracranial arteriovenous malformation using stereotactic radiosurgery or hypofractionated stereotactic radiotherapy.

PURPOSE: To investigate the appropriateness of the treatment policy of stereotactic irradiation using both hypofractionated stereotactic radiotherapy (HSRT) and stereotactic radiosurgery (SRS) for arteriovenous malformations (AVMs) located in an eloquent region or for large AVMs and using SRS alone for the other AVMs. METHODS AND MATERIALS: Included in this study were 75 AVMs in 72 patients, with a mean follow-up of 52 months. Of the 75 AVMs, 33 were located in eloquent regions or were >2.5 cm in maximal diameter and were given 25-35 Gy (mean, 32.4 Gy) in four daily fractions at a single isocenter if the patient agreed to prolonged wearing of the stereotactic frame for 5 days. The other 42 AVMs were treated with SRS at a dose of 15-25 Gy (mean, 24.1 Gy) at the isocenter. The 75 AVMs were classified according to the Spetzler-Martin grading system; 21, 23, 28, 2, and 1 AVM were Grade I, II, III, IV, V, and VI, respectively. RESULTS: The overall actuarial rate of obliteration was 43% (95% confidence interval [CI], 30-56%) at 3 years, 72% (95% CI, 58-86%) at 5 years, and 78% (95% CI, 63-93%) at 6 years. The actuarial obliteration rate at 5 years was 79% for the 42 AVMs <2.0 cm and 66% for the 33 AVMs >2 cm. The 5- and 6-year actuarial obliteration rate was 61% (95% CI, 39-83%) and 71% (95% CI, 47-95%), respectively, after HSRT and 81% (95% CI, 66-96%) and 81% (95% CI, 66-96%), respectively, after SRS; the difference was not statistically significant. Radiation-induced necrosis was observed in 4 subjects in the SRS group and 1 subject in the HSRT group. Cyst formation occurred in 3 patients in the SRS group and no patient in the HSRT group. A permanent symptomatic complication was observed in 3 cases (4.2%), and 1 of the 3 was fatal. All 3 patients were in the SRS group. The annual intracranial hemorrhage rate was 5.5-5.6% for all patients. CONCLUSION: Our treatment policy using SRS and HSRT was as effective as the policy involving SRS alone. The HSRT schedule was suggested to have a lower frequency of radiation necrosis and cyst formation than the high-dose SRS schedule. The benefit of HSRT compared with lower dose SRS has not yet been determined.

Effect of treatment time on outcome of radiotherapy for oral tongue carcinoma.

PURPOSE: To investigate the importance of total treatment time on the outcome of external beam radiotherapy (EBRT) followed by internal brachytherapy for the treatment of oral tongue carcinoma. METHODS AND MATERIALS: Ninety-four patients with T1-T2N0 squamous cell carcinoma of the oral tongue were treated using 35-40 Gy EBRT followed by 35-40 Gy interstitial (137)Cs brachytherapy between 1985 and 1995. The interval between the end of EBRT and the start of interstitial treatment varied for numerous unavoidable reasons, with a mean of 25.3 days and standard deviation of 3.5 days. The median follow-up period was 59.1 months (range 6-146). RESULTS: The actuarial survival rate of all cases was 78.4% at 5 years. The 5-year local control rate for those with T1 and T2 was 92.8% and 62.7%, respectively (p < 0.05). The local control rate of the primary tumor in patients with a total treatment time >43 days was statistically lower than that of patients with a total treatment time < or =43 days in all patients (p < 0.05) and in the subgroup of Stage T2 patients (p < 0.05). Multivariate analysis revealed that the local control rates in all cases were significantly related to the T stage (T2 or not), total treatment time (>43 days or not), and location of disease (posterior or not). Regression analysis for 5-year local control as a function of treatment duration showed a 2% loss of local control per day of treatment extension >30 days (r = 0.94, p < 0.01). CONCLUSION: The total treatment time was associated with the local control rate in the RT of oral tongue carcinoma. The loss in local control was estimated to be 2.0% per additional day in our series for oral tongue carcinoma.

Image fusion between 18FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas.

PURPOSE: Accurate diagnosis of tumor extent is important in three-dimensional conformal radiotherapy. This study reports the use of image fusion between (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) and magnetic resonance imaging/computed tomography (MRI/CT) for better targets delineation in radiotherapy planning of head-and-neck cancers. METHODS AND MATERIALS: The subjects consisted of 12 patients with oropharyngeal carcinoma and 9 patients with nasopharyngeal carcinoma (NPC) who were treated with radical radiotherapy between July 1999 and February 2001. Image fusion between 18FDG-PET and MRI/CT was performed using an automatic multimodality image registration algorithm, which used the brain as an internal reference for registration. Gross tumor volume (GTV) was determined based on clinical examination and 18FDG uptake on the fusion images. Clinical target volume (CTV) was determined following the usual pattern of lymph node spread for each disease entity along with the clinical presentation of each patient. RESULTS: Except for 3 cases with superficial tumors, all the other primary tumors were detected by 18FDG-PET. The GTV volumes for primary tumors were not changed by image fusion in 19 cases (89%), increased by 49% in one NPC, and decreased by 45% in another NPC. Normal tissue sparing was more easily performed based on clearer GTV and CTV determination on the fusion images. In particular, parotid sparing became possible in 15 patients (71%) whose upper neck areas near the parotid glands were tumor-free by 18FDG-PET. Within a mean follow-up period of 18 months, no recurrence occurred in the areas defined as CTV, which was treated prophylactically, except for 1 patient who experienced nodal recurrence in the CTV and simultaneous primary site recurrence. CONCLUSION: This preliminary study showed that image fusion between 18FDG-PET and MRI/CT was useful in GTV and CTV determination in conformal RT, thus sparing normal tissues.

Tolerance of organs at risk in small-volume, hypofractionated, image-guided radiotherapy for primary and metastatic lung cancers.

PURPOSE: To determine the organ at risk and the maximum tolerated dose (MTD) of radiation that could be delivered to lung cancer using small-volume, image-guided radiotherapy (IGRT) using hypofractionated, coplanar, and noncoplanar multiple fields. MATERIALS AND METHODS: Patients with measurable lung cancer (except small-cell lung cancer) 6 cm or less in diameter for whom surgery was not indicated were eligible for this study. Internal target volume was determined using averaged CT under normal breathing, and for patients with large respiratory motion, using two additional CT scans with breath-holding at the expiratory and inspiratory phases in the same table position. Patients were localized at the isocenter after three-dimensional treatment planning. Their setup was corrected by comparing two linacographies that were orthogonal at the isocenter with corresponding digitally reconstructed images. Megavoltage X-rays using noncoplanar multiple static ports or arcs were used to cover the parenchymal tumor mass. Prophylactic nodal irradiation was not performed. The radiation dose was started at 60 Gy in 8 fractions over 2 weeks (60 Gy/8 Fr/2 weeks) for peripheral lesions 3.0 cm or less, and at 48 Gy/8 Fr/2 weeks at the isocenter for central lesions or tumors more than 3.0 cm at their greatest dimension. RESULTS: Fifty-seven lesions in 45 patients were treated. Tumor size ranged from 0.6 to 6.0 cm, with a median of 2.6 cm. Using the starting dose, 1 patient with a central lesion died of a radiation-induced ulcer in the esophagus after receiving 48 Gy/8 Fr at isocenter. Although the contour of esophagus received 80% or less of the prescribed dose in the planning, recontouring of esophagus in retrospective review revealed that 1 cc of esophagus might have received 42.5 Gy, with the maximum dose of 50.5 Gy. One patient with a peripheral lesion experienced Grade 2 pain at the internal chest wall or visceral pleura after receiving 54 Gy/8 Fr. No adverse respiratory reaction was noted in the symptoms or respiratory function tests. The 3-year local control rate was 80.4% +/- 7.1% (a standard error) with a median follow-up period of 17 months for survivors. Because of the Grade 5 toxicity, we have halted this Phase I/II study and are planning to rearrange the protocol setting accordingly. The 3-year local control rate was 69.6 +/- 10.6% for patients who received 48 Gy and 100% for patients who received 60 Gy (p = 0.0442). CONCLUSIONS: Small-volume IGRT using 60 Gy in eight fractions is highly effective for the local control of lung tumors, but MTD has not been determined in this study. The organs at risk are extrapleural organs such as the esophagus and internal chest wall/visceral pleura rather than the pulmonary parenchyma in the present protocol setting. Consideration of the uncertainty in the contouring of normal structures is critically important, as is uncertainty in setup of patients and internal organ in the high-dose hypofractionated IGRT.

Acute adverse effects of radiation therapy on HIV-positive patients in Japan: study of 31 cases at Tokyo Metropolitan Komagome Hospital.

Recently, the number of human immunodeficiency virus (HIV) -positive patients has increased in Japan. HIV-positive patients are at a higher risk of cancer than the general population. This paper retrospectively reports the acute adverse effects of radiation therapy on HIV-positive patients who were treated at Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital (TMCICK). Thirty-one cases involving 24 HIV-positive cancer patients who were treated at TMCICK from January 1997 to March 2009 were included in this study. All acute adverse effects of radiation therapy were examined during, and one month after, the last radiation therapy session. Acute adverse effects were classified according to the site of radiation therapy treatment and analyzed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Grade 3 acute adverse effects were seen in 17% of cases, and Grade 2 toxicities were found in 23% of patients. Damage to the skin and mucosa, including stomatitis or diarrhea, tended to occur after low-dose radiation therapy; however, no severe acute adverse effects were seen in other organs, such as the brain, lung, and bone. Acute adverse effects tended to occur earlier in HIV-positive patients and became severe more frequently than in the general population. In particular, disorders of the mucosa, such as those of the oral cavity, pharynx, and intestine, tended to occur rapidly. It was shown that radiation therapy is safe when treatment is performed carefully and that it is a very useful treatment for cancer in HIV-positive patients.

Hyperthermia combined with intra-thoracic chemotherapy and radiotherapy for malignant pleural mesothelioma.

BACKGROUND: Prognosis for patients with malignant pleural mesothelioma (MPM) remains poor and such patients require intensive treatment. Few studies have examined hyperthermia for MPM. The present study investigated the feasibility of hyperthermia combined with weekly chemo-radiotherapy for patients with MPM and estimated the efficacy of this regimen. METHODS: A total of 11 patients (median patient age was 67 and all had pleural effusion) with MPM were enrolled in this study. The treatment regimen comprised of weekly thermo-radiotherapy with intra-thoracic chemotherapy 2-5 times at initiation of treatment. Hyperthermia was performed once per week for approximately 60 min. Hemithorax external radiotherapy was administered once weekly on the same day as hyperthermia and just before thermochemotherapy. Median total radiation dose was 6 Gy (range, 2-10 Gy). Chemotherapy was administered into the thoracic cavity through a tube. Chemotherapeutic agents administered were CDDP for seven patients, carboplatinum (CBDCA) for three patients and both CDDP and CBDCA for one patient. Dose of CDDP was 50 mg/body and dose of CBDCA was 200-300 mg m-2. Response rate and median survival time (MST) and palliative effect were investigated. RESULTS: Complete response was not achieved in any of the 11 patients. Partial response was achieved in three of 11 patients (27.3%), SD in six patients (54.5%) and PD in two patients (18.2%). There was no correlational relationship between thermal parameters and response. MST was 27.1 months. Pleural fluid decreased in all patients after therapy, while all patients displayed improved performance status and could be discharged from hospital. Patients with partial response had a relatively longer survival time than SD or PD. All patients underwent the complete course of treatment and only one of 11 patients developed grade 4 thrombocytopenia. CONCLUSION: It was therefore concluded that hyperthermia combined with intra-thoracic chemotherapy using cisplatinum or carboplatinum may be tolerable. This approach appears effective and more acceptable for patients with MPM with pleural effusion than other multi-modality therapy.