A phase II study of palliative radiotherapy combined with zoledronic acid hydrate for metastatic bone tumour from renal cell carcinoma.

PURPOSE: Palliative radiotherapy is the standard of care for bone metastases. However, skeletal-related events, defined as a pathologic fracture, paraplegia, surgery or radiotherapy for local recurrence, or severe pain in previously irradiated bone with radio-resistant histology type still present high incidence. The primary objective of this study was to determine whether zoledronic acid hydrate and palliative radiotherapy could prevent local skeletal-related events. METHODS: Eligible patients with bone metastases from renal cell carcinoma were treated with zoledronic acid hydrate every 3 or 4 weeks and concurrent palliative radiotherapy of 30 Gy in 3 Gy fractions. The criteria for radiotherapy were established by the treating physician, but patients with complicated bone metastases (impending pathological fracture or spinal cord compression) which needed immediate surgery were excluded. The primary endpoint was the local skeletal-related event-free survival rate at 1 year. RESULTS: Twenty-seven patients were included in the study. The median age was 65 (range, 50-84) years. Radiotherapy dose was 30 Gy for all patients except 1 whose radiotherapy was terminated due to brain metastasis progression at 18 Gy. Zoledronic acid hydrate was administered in a median of 12 (range, 0-34) times. The median follow-up period was 12 months and 19 months in patients who were still alive. Of 27 patients in the efficacy analysis, the 1-year local skeletal-related event-free rate was 77.6% (80% confidence interval, 66.2-89.0). Common grade 3 toxicities were hypocalcemia (1 [4%]), sGPT level increase (1 [4%]) and sGOT level increase (1 [4%]). There was no grade 4 or 5 toxicity. CONCLUSION: Zoledronic acid hydrate administration and palliative radiotherapy were a well-tolerated and promising treatment reducing skeletal-related events for bone metastases from renal cell carcinoma.

[A Patient with Breast Cancer Who Achieved Continued Clinical Complete Response after Systemic Therapy Alone].

A 53-year-old woman presented at our hospital because of a mass in the left breast. A mass measuring 2 cm in diameter was palpated in the upper outer region(C region)of the left breast. Mammography showed a mass with calcification. Mammary ultrasonography showed a mass measuring 18×16×14mm and enlarged lymph nodes in the left axillary region. Core needle biopsy revealed Luminal B invasive ductal carcinoma(scirrhous type). The estrogen receptor(ER)positivity was 95%, progesterone receptor(PgR)positivity was 60%, human epidermal growth factor receptor type 2(HER2)score was 2+, fluorescence in situ hybridization(FISH)showed no amplification, and Ki-67 index was 60%. Clinical T1N1M0, StageⅡA cancer was thus diagnosed. As preoperative chemotherapy, the patient received 4 courses of treatment containing epirubicin (100mg/m2), 5-fluorouracil(500mg/m2), and cyclophosphamide(500mg/m2; FEC100), and 4 courses of treatment containing docetaxel and cyclophosphamide(TC). Clinical complete response(cCR)was confirmed on imaging studies. The patient was explained about the need for surgery, but she refused to undergo surgery. The patient is being followed up while receiving endocrine therapy, and there has been no recurrence or metastasis as of 2 years. We described our encounter with a patient with breast cancer who refused surgery after preoperative chemotherapy and has had no recurrence or metastasis during follow-up.

The role of prophylactic cranial irradiation for patients with small-cell lung cancer.

Small-cell lung cancer (SCLC) has a particular propensity to metastasize to the brain, affecting ~10% of SCLC patients at diagnosis, but may occur in more than 50% of 2-year survivors. Most cytotoxic drugs have limited ability to cross the blood-brain barrier, and the effectiveness of chemotherapy for brain metastasis is limited. Therefore, prophylactic cranial irradiation (PCI) has been proposed to treat SCLC. A meta-analysis revealed that PCI significantly decreased the risk of brain metastasis and increased the 3-year survival rate; it has been established as a standard therapy for limited-disease SCLC. However, certain aspects of PCI remain unclarified, including the roles in resected SCLC and extensive-disease SCLC, and its neurotoxicities. In addition, information on PCI has been obtained from old clinical trials without the use of new imaging devices, such as magnetic resonance imaging. Evidence from advanced imaging techniques is needed in this era.

Impact of five-tiered Gleason grade groups on prognostic prediction in clinical stage T3 prostate cancer undergoing high-dose-rate brachytherapy.

BACKGROUND: We evaluated a five-tiered Gleason grade groups arising from the 2014 International Society of Urological Pathology consensus conference on prognostic prediction in clinical stage T3a (extracapsular invasion) and T3b (seminal vesicle involvement) prostate cancer undergoing high-dose-rate brachytherapy (HDR-BT). METHODS: From November 2003 to December 2012, 283 patients with stage T3 prostate cancer received HDR-BT and external beam radiation therapy (EBRT) with long-term androgen deprivation therapy (ADT). Of these, 203 (72%) and 80 (28%) patients had stage T3a and T3b disease, respectively. The mean dose to 90% of the planning target volume was 7.5 Gy/fraction of HDR-BT. After five fractions, EBRT with 10 fractions of 3 Gy was administered. All patients first underwent ≥6 months of neoadjuvant ADT, and adjuvant ADT continued for 36 months. Median follow-up was 74 months from the start of radiotherapy. RESULTS: The 10-year biochemical recurrence (BCR) -free rate for stage T3a and T3b disease was 79% and 64%, respectively (P = 0.0083). The 10-year cancer-specific survival (CSS) rate for stage T3a and T3b was 96% and 91%, respectively (P = 0.0305). Although grade groups ≥4 were independent predictors for BCR in cT3a patients (P = 0.0270), they failed to significantly predict prostate cancer-specific mortality (PCSM) among cT3a patients. Among cT3b patients, grade group 5 was a significant predictor of both BCR (P = 0.0017) and PCSM (P = 0.0233). Among stage T3a patients, no significant difference existed in 10-year CSS between grade groups 5 and 4 (94% vs 97%, P = 0.3960). In contrast, grade group 5 had a significantly worse outcome in 10-year CSS than grade group 4 among stage T3b patients (74% vs 100%, P = 0.0350). CONCLUSIONS: Stage T3a patients with grade groups 4/5 and stage T3b with grade group 4 had fairly low PCSM risk. Approximately one of four patients among stage T3b patients with grade group 5 showed PCSM after combined HDR-BT and EBRT with long-term ADT. Stage T3b patients with grade group 5 may have a greater risk for PCSM.

Retrospective analysis of definitive radiotherapy for neck node metastasis from unknown primary tumor: Japanese Radiation Oncology Study Group study.

OBJECTIVE: To investigate the optimal treatment method and risk factor of neck node metastasis from unknown primary tumors (NUP) treated by radiotherapy. METHODS: Retrospective case study based on a multi-institutional survey was conducted by the Japanese Radiation Oncology Study Group. Patients pathologically diagnosed as having NUP from 1998 to 2007 were identified. Univariate and multivariate analyses of overall survival (OS), progression free survival (PFS), neck progression free survival (NPFS) and mucosal progression free survival (MPFS) were evaluated. RESULTS: In total, 130 patients with median age of 65 years were included. Nodal stages N1, N2a, N2b and N2c were observed for 10, 26, 43, 12 and 39 patients, respectively. All the patients received radiotherapy (RT) with neck dissection in 60 and with chemotherapy in 67 cases. The median doses to the metastatic nodes, prophylactic neck and prophylactic mucosal sites were 60.0, 50.4 and 50.4 Gy, respectively. The median follow-up period for surviving patients was 42 months. Among 12 patients, occult primary tumors in the neck region developed after radiotherapy. The 5-year OS, PFS, NPFS and MPFS were 58.1%, 42.4%, 47.3% and 54.9%, respectively. Univariate analysis showed that lower N stage (N1-2b), non-bulky node (<6 cm) and negative extracapsular extension (ECE) status were the factors associated with favorable OS, PFS, NPFS and MPFS. Radical surgery proved to be a favorable factor of OS, NPFS and MPFS. On multivariate analysis, lower N stage and negative ECE status were correlated with improved survival. CONCLUSIONS: Lower nodal stage and negative ECE status showed a favorable impact on survival and disease control in patients with NUP treated by radiotherapy.

Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer.

Despite the absence of local prostate cancer recurrence, some patients develop distant metastases after prostate brachytherapy. We evaluate whether prostate brachytherapy procedures have a potential risk for hematogenous spillage of prostate cancer cells. Fifty-nine patients who were undergoing high-dose-rate (HDR) or low-dose-rate (LDR) brachytherapy participated in this prospective study. Thirty patients with high-risk or locally advanced cancer were treated with HDR brachytherapy after neoadjuvant androgen deprivation therapy (ADT). Twenty-nine patients with clinically localized cancer were treated with LDR brachytherapy without neoadjuvant ADT. Samples of peripheral blood were drawn in the operating room before insertion of needles (preoperative) and again immediately after the surgical manipulation (intraoperative). Blood samples of 7.5 mL were analyzed for circulating tumor cells (CTCs) using the CellSearch System. While no preoperative samples showed CTCs (0%), they were detected in intraoperative samples in 7 of the 59 patients (11.8%; preoperative vs. intraoperative, p = 0.012). Positive CTC status did not correlate with perioperative variables, including prostate-specific antigen (PSA) at diagnosis, use of neoadjuvant ADT, type of brachytherapy, Gleason score, and biopsy positive core rate. We detected CTCs from samples immediately after the surgical manipulation. Further study is needed to evaluate whether those CTCs actually can survive and proliferate at distant sites.

[Which Should be Treated First - Breast Cancer or Uterine Myoma?]

The patient was a 51-year-old woman with a mass in the left breast.At the first presentation, she had abdominal distension and liver dysfunction.Mammography showed a category 5 mass in the left breast and a category 4, unstructured region in the right breast.Pathological examination revealed bilateral, invasive ductal carcinomas.Stage II B disease(clinical T2N1M0)was diagnosed in the left breast, and Stage I disease(clinical T1N0M0)was diagnosed in the right breast.Computed tomography revealed a massive uterine myoma compressing the inferior vena cava.Liver dysfunction was suspected to be caused by these factors.Preoperative chemotherapy was scheduled to treat breast cancer.A gynecologist stated that "uterine myoma is unlikely to cause liver dysfunction" and refused to perform a hysterectomy.However, we diligently negotiated with him to avoid chemotherapy-induced venous thrombosis and pulmonary infarction; eventually, a hysterectomy(3.6 kg)was performed. After surgery, liver function was normal.Subsequently, breast cancer could be safely and adequately treated.In patients who have benign disease, as well as malignant tumors, treatment of the malignant tumors is generally given the highest priority.However, there are cases when the treatment of benign disease has priority over the treatment of malignant tumors.It is therefore important to intensively discuss such cases with physicians from other departments.

[A Patient with a Pathological Complete Response to Neo-Adjuvant Chemotherapy for Triple-Negative Breast Cancer Followed by Recurrence after Six Months].

The patient was a 68-year-old woman who received neo-adjuvant chemotherapy(4 courses of weekly paclitaxel plus bevacizumab and 4 courses of 5-fluorouracil epirubicin, and cyclophosphamide)for cT1N1M0, Stage II A right-sided triplenegative breast cancer(TNBC). Right breast-conserving surgery with axillary lymph-node dissection was performed. The postoperative pathological diagnosis was a complete response. Six months after surgery, the patient developed lower and right-sided back pain. Detailed examination revealed multiple metastases to the liver, bone, lymph nodes of the mediastinum, and bile duct. The recurrence was treated with biweekly paclitaxel plus bevacizumab. The patient's pain dramatically improved. However, the duration of the response was only 3 months. The patient received eribulin as a second-line treatment, but did not respond and subsequently died. TNBC is considered to have relatively good outcomes if a pathological complete response(pCR)is obtained after preoperative chemotherapy. However, recurrence occurred after only 6months in our patient. In patients with TNBC, physical examinations and simple laboratory tests should be performed every 1 to 2 months after surgery, even if a pathological complete response is obtained. We used paclitaxel plus bevacizumab to treat recurrence of TNBC. Although this treatment did not prolong overall or disease-free survival, the patient temporarily responded, and her quality of life was maintained. Further studies are needed to elucidate the pathogenesis of TNBC and to develop more effective treatments.

Prevalent and up-regulated vimentin expression in micropapillary components of lung adenocarcinomas and its adverse prognostic significance.

The factors conferring the increased malignancy on lung adenocarcinoma with micropapillary component (AC-MPC) remain to be elucidated. On proteomics based on 2-dimensional gel electrophoresis, 19 proteins differentially expressed by more than 1.5-fold between AC-MPC and conventional adenocarcinoma (CAC); in particular, vimentin, one of the proteins, was 3.5-fold up-regulated in AC-MPC. Subsequent semi-quantitative investigation by immunohistochemistry with large cohorts comprised 101 AC-MPC and 119 CAC, respectively, of different stages revealed that vimentin was expressed in MPC of 95 (94.1%) AC-MPC and the expression scores were higher than those of well- and moderately differentiated CAC, as well as the background non-MPC of the AC-MPC (P < 0.0001), but not significantly different from those of poorly differentiated CAC (P = 0.561). Even within the AC-MPC entity, higher vimentin expression was correlated with more frequent vascular invasion and more advanced node metastasis (P < 0.02), and multivariate analysis showed that high vimentin expression and worse node statuses were independent indicators of adverse prognosis (P < 0.048). In conclusion, vimentin expression is prevalent and markedly up-regulated in MPC, which might reflect the biological essence of poorer differentiation or dedifferentiation of MPC, and this might have a role in the acquisition and increase of invasiveness and consequent more malignant nature of MPC.

Radiotherapy for patients with unresectable advanced hepatocellular carcinoma with invasion to intrahepatic large vessels: efficacy and outcomes.

BACKGROUND AND AIM: To examine the efficacy and outcomes of radiotherapy (RT) in patients who have hepatocellular carcinoma with invasion to intrahepatic large vessels (IHLVs). METHODS: Sixty-seven patients who had advanced hepatocellular carcinoma with invasion to IHLVs received three-dimensional conformal RT. IHLV invasion was associated with portal venous tumor thrombosis in 40 patients, tumor thrombosis involving the hepatic vein in 17, and both findings in 10. A daily radiation dose of 1.8-2 Gy was administered using 6 or 10 MV X-rays to deliver a total dose of 30-56 Gy. RESULTS: The overall objective response rate (complete response plus partial response) was 45% (n = 30). The median survival time was 13.7 months in the responder group and 5.9 months in the nonresponder group. An objective response was observed in 28 (56%) of 50 patients with Child-Pugh (C-P) class A and in 2 (12%) of 17 patients with C-P class B. Hepatic function of C-P class A was an independent factor for both RT responder and overall survival on Cox regression analysis (hazard ratio = 9.5, 95% confidence interval = 1.97-46.2, P = 0.005; and hazard ratio = 0.39, 95% confidence interval = 0.2-0.77, P = 0.007, respectively). CONCLUSION: RT is an effective treatment option without serious adverse events. RT should be considered for the patients with better hepatic function who have invasion to IHLVs.

Clinical outcomes of 849 laryngeal cancers treated in the past 40 years: are we succeeding?

OBJECTIVE: We analyzed the clinical outcomes of 849 laryngeal cancers treated in the past 40 years, which overlapped with the era of the global treatment shift. METHODS: To compare the chronological outcomes, patients were divided into four groups according to their registration year as 1972-82, 1983-92, 1993-2002 and 2003-12; treatment trends, larynx preservation rate and overall survival rate were compared. RESULTS: There were 104, 173, 253 and 319 patients registered in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. Five-year overall survival rates were 74, 76.5, 75.6 and 82.2% in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. The five-year larynx preservation rates were 65.5, 75.7, 75.4 and 80.9% in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. CONCLUSIONS: The number of patients treated at our institute increased, and the overall survival and larynx preservation rates exhibited favorable improvements over the past four decades. In the analysis of nonsurgical options, S1 combined radiotherapy showed superiority over concurrent chemoradiotherapy and radiotherapy in larynx preservation, and S1 combined radiotherapy, concurrent chemoradiotherapy and Tegafur Uracil combined radiotherapy showed superiority over radiotherapy in overall survival. In nonsurgical approaches, proper case selection is the key to success and may be much more important than pursuing radiotherapy dose escalation. In the analysis of surgical options, laser and supracricoid laryngectomy with cricohyoidoepiglottopexy contributed to larynx preservation in early- and intermediate-stage cancers, respectively. Supracricoid laryngectomy with cricohyoidoepiglottopexy demonstrated overall survival not worse than total laryngectomy, which is the prerequisite treatment basis for larynx preservation options. We must make extra efforts in pursuing an ideal balance between nonsurgical and surgical larynx preservation options.

High-dose-rate intra-cavitary brachytherapy combined with external beam radiation therapy for under 40-year-old patients with invasive uterine cervical carcinoma: clinical outcomes in 118 Patients in a Japanese multi-institutional study, JASTRO.

BACKGROUND: The current study was designed to evaluate the clinical outcomes of curative intent radiation therapy for young patients with invasive uterine cervical carcinoma in Japan. METHODS: One hundred and eighteen patients aged ≤40 were registered in the multi-institutional study of the Japanese Society of Therapeutic Radiology and Oncology (JASTRO) from 26 major institutions in Japan. The age range was 24-39 years and the maximum tumor diameter was 2.0-9.2 cm. The International Federation of Gynecology and Obstetrics clinical stages were Ib, IIa, IIb, IIIa, IIIb and IVa in 17, 6, 40, 2, 50 and 3, respectively. Curative intent radiation therapy consisted of the combination of external beam radiation therapy and high-dose rate intra-cavitary brachytherapy. The total dose of external beam radiation therapy ranged between 44 and 68 Gy. Both the median and mode of total high-dose-rate intra-cavitary brachytherapy dose to point A were 24 Gy in four fractions. Ninety-six patients (58%) received chemotherapy. RESULTS: The 5-year overall survival rate and local control rate of all patients were 61 and 65%, respectively. The 5-year overall survival rates of International Federation of Gynecology and Obstetrics Stage Ib, IIa, IIb, IIIa, IIIb and IVa were 88, 100, 75, 100, 37 and 0%, respectively. The 5-year local control rates of International Federation of Gynecology and Obstetrics Stage Ib, IIa, IIb, IIIa, IIIb and IVa were 82, 75, 75, 100, 51 and 0%, respectively. Sixteen patients experienced grade 3 or greater late radiation morbidity. CONCLUSIONS: The 5-year overall survival rate of young patients with Stage IIIb was comparatively low at 37%.

Functional organ preservation for laryngeal cancer: past, present and future.

OBJECTIVE: Management of laryngeal cancer has focused on improving survival while preserving function. Over the past 20 years, the trends have shifted from surgery to chemoradiotherapy and presently we are facing various challenges. It is imperative to re-examine what has happened and what can be done. METHODS: Review of the literature along with our experience in the management of functional organ preservation for laryngeal cancer. RESULTS: There was an increasing use of chemoradiotherapy with a decreasing use of surgery. Inappropriate patient selection along with inability to properly apply salvage surgeries have been presumed to be responsible for survival deterioration in laryngeal cancer. Reports concerning late adverse events after chemoradiotherapy are also increasing. Reconfirmation of the multidisciplinary team approach is imperative. Transoral laser microsurgery can be used for early laryngeal cancer and, in some experienced institutes, for advanced-stage cancers. Supracricoid laryngectomy demonstrated satisfactory oncologic and functional outcomes, based on our experience. CONCLUSIONS: Treatment selection for larynx preservation should not merely be decided by guidelines but considering each patient's individual condition. Head and neck surgeons are encouraged to take reasonable risks in performing salvage larynx preservation surgery when it is the only option to save a functioning larynx.

Radiotherapy quality assurance review for a multi-center randomized trial of locally advanced esophageal cancer: the Japan Clinical Oncology Group (JCOG) trial 0303.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the radiotherapy (RT) quality assurance (QA) for JCOG 0303. METHODS AND MATERIALS: JCOG 0303 was a multi-center phase II/III trial that compared two types of chemotherapy administered concomitantly with RT for locally advanced esophageal cancer. RT requirements included a total dose of 60 Gy in 30 fractions and CTV with a 2-cm margin cranio-caudally to the primary tumor. The QA assessment was given as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable following predefined criteria for quality parameters. RESULTS: A total of 142 cases were accrued. After excluding 36 incomplete/not evaluable, 106 (75%) were fully evaluable for RT quality review. Of these 106, there were 4 VU (4%) and overall RT compliance (PP + DA) was 96%. Comparing the incidence of VU based on the numbers enrolled by institution, the highest quarter of enrollment (≥7 cases) had no VU, while all VU (4; 11%) were from institutions enrolling <7 patients. CONCLUSIONS: The results of the RTQA assessment for JCOG 0303 were sufficient to provide reliable results. Additional improvements will be needed for institutions with low accrual rates.

Three-dimensional dose-distribution measurement of therapeutic carbon-ion beams using a ZnS scintillator sheet.

The accurate measurement of the 3D dose distribution of carbon-ion beams is essential for safe carbon-ion therapy. Although ionization chambers scanned in a water tank or air are conventionally used for this purpose, these measurement methods are time-consuming. We thus developed a rapid 3D dose-measurement tool that employs a silver-activated zinc sulfide (ZnS) scintillator with lower linear energy transfer (LET) dependence than gadolinium-based (Gd) scintillators; this tool enables the measurement of carbon-ion beams with small corrections. A ZnS scintillator sheet was placed vertical to the beam axis and installed in a shaded box. Scintillation images produced by incident carbon-ions were reflected with a mirror and captured with a charge-coupled device (CCD) camera. A 290 MeV/nucleon mono-energetic beam and spread-out Bragg peak (SOBP) carbon-ion passive beams were delivered at the Gunma University Heavy Ion Medical Center. A water tank was installed above the scintillator with the water level remotely adjusted to the measurement depth. Images were recorded at various water depths and stacked in the depth direction to create 3D scintillation images. Depth and lateral profiles were analyzed from the images. The ZnS-scintillator-measured depth profile agreed with the depth dose measured using an ionization chamber, outperforming the conventional Gd-based scintillator. Measurements were realized with smaller corrections for a carbon-ion beam with a higher LET than a proton. Lateral profiles at the entrance and the Bragg peak depths could be measured with this tool. The proposed method would make it possible to rapidly perform 3D dose-distribution measurements of carbon-ion beams with smaller quenching corrections.

Phase 2 Study of Nimotuzumab in Combination With Concurrent Chemoradiotherapy in Patients With Locally Advanced Non-Small-Cell Lung Cancer.

BACKGROUND: We evaluated the tolerability and efficacy of nimotuzumab, a humanized IgG1 monoclonal anti-epidermal growth factor receptor antibody, with concurrent chemoradiotherapy in patients with unresectable locally advanced non-small-cell lung cancer. PATIENTS AND METHODS: In this multicenter, single-arm, open-label, phase 2 trial conducted in Japan (JapicCTI-090825), patients received thoracic radiotherapy (60 Gy, 2 Gy per fraction, 6 weeks) and four 4-week cycles of chemotherapy (day 1, cisplatin 80 mg/m2; days 1 and 8, vinorelbine 20 mg/m2). Nimotuzumab 200 mg was administrated weekly for 16 weeks. The primary endpoint was treatment completion rate, defined as the percentage of patients completing 60 Gy of radiotherapy within 8 weeks, 2 cycles of chemotherapy, and at least 75% of the required nimotuzumab dose during the initial 2-cycle concurrent chemoradiotherapy period. RESULTS: Of 40 patients enrolled, 39 received the study treatment, which was well tolerated, with a completion rate of 87.2%. Thirty-eight patients completed 60 Gy of radiotherapy within 8 weeks. Infusion reaction, grade 3 or higher rash, grade 3 or higher radiation pneumonitis, or grade 4 or higher nonhematologic toxicity were not observed. The objective response rate was 69.2%. The median progression-free survival (PFS) and 5-year PFS rate were 508 days and 29.0%, respectively. The 5-year PFS rate in patients with non-squamous cell carcinoma (n = 23) was 13.7% and in patients with squamous cell carcinoma (n = 16) was 50.0%. The 5-year overall survival rate was 58.4%. CONCLUSION: Addition of nimotuzumab to the concurrent chemoradiotherapy regimen was well tolerated and showed potential for treating patients with locally advanced non-small-cell lung cancer, particularly squamous cell carcinoma.

Oligometastases and oligo-recurrence: the new era of cancer therapy.

Recurrence or metastasis of cancer has been considered to occur in the last stage of the patient's life. However, the new notions of oligometastases and oligo-recurrence have been proposed and the paradigm shift in the conceptualization of cancer metastasis or cancer recurrence. Oligometastases is the state in which the patient shows distant relapse in only a limited number of regions. Local therapy such as surgery, radiotherapy and radiofrequency ablation for the relapsed sites could thus improve patient's survival. On the other hand, oligo-recurrence is a notion similar to oligometastases. However, the conditions of oligo-recurrence has a primary site of the cancer controlled, meaning that all gross recurrent or metastatic sites could be treated using local therapy.

Phase I/II trial of concurrent use of S-1 and radiation therapy for T2 glottic cancer.

OBJECTIVE: A Phase I/II study of S-1 combined radiation therapy was conducted in patients with Stage II (T2N0) glottic cancer. The purpose of the Phase I study was to identify the maximum tolerated dose, the recommended dose and the dose limiting toxicity. The objectives in the phase II study were to estimate the local control and the overall survival, and the incidence of adverse events. METHODS: In Phase I, S-1 was administered orally in a split-course fashion as two doses of 40 mg/m(2), for a total daily dose of 80 mg/m(2). The course involved a 2-week rest after a 2-week administration (Level 1) and a 1-week rest after a 3-week administration (Level 2). Radiation therapy was administered in 2-Gy daily (total 60-Gy) standard fractionation. RESULTS: Seven patients were enrolled in the Phase I, and 19 in the Phase II study. Mucositis was the most common toxicity encountered. All 26 patients completed radiation therapy without delay. The overall response rate was 100% (26/26) with all patients showing a complete response. One patient developed a local recurrence 28 months after the treatment. The 3-year local control and overall survival rates were 94.7 and 85.4%, respectively (limited to 22 patients from Level 2). CONCLUSIONS: The use of S-1 at 80 mg/m(2) per day in a split-course with 1-week rest during the course of radiation therapy was safe and effective for Stage II glottic cancer. The treatment strategy employing orally available S-1 proved to be beneficial over the conventional injection of antitumor agents for maintaining the patients' quality of life.

High-dose-rate intracavitary brachytherapy combined with external beam radiotherapy for stage IIIb adenocarcinoma of the uterine cervix in Japan: a multi-institutional study of Japanese Society of Therapeutic Radiology and Oncology 2006-2007 (study of JASTRO 2006-2007).

OBJECTIVE: The current study was a retrospective questionnaire survey of stage IIIb adenocarcinoma of the uterine cervix treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in Japan aimed to investigate the optimal dose on the basis of the biological effective dose and prognostic factors. METHODS: Between 1990 and 2000, 61 patients with stage IIIb adenocarcinoma of the uterine cervix underwent high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy in 19 major hospitals in Japan. This retrospective questionnaire survey was performed by mail including survey charts to be fulfilled by radiation oncologists in these 19 major hospital. Fifty had only adenocarcinoma components and 11 had adenosquamous cell carcinoma components. All patients were treated with high-dose-rate intracavitary brachytherapy combined with external beam radiation therapy. Total biological effective dose (T-BED(10)) was calculated from the sum of the biological effective doses of the external beam radiation therapy and the intracavitary brachytherapy. Thirty-two patients underwent chemotherapy. RESULTS: The 5-year overall survival rate of all patients was 20.2%. Stratified by total biological effective dose, the 5-year overall survival rate was 0% for T-BED(10) <75 Gy, 24.7% for T-BED(10) between 75 and 100 Gy and 0% for T-BED(10) >110 Gy (P = 0.15). Stratified by histopathology, the 5-year overall survival rate was 22.1% for adenocarcinoma and 13.6% for adenosquamous cell carcinoma (P = 0.43). Stratified by chemotherapy, the 5-year overall survival rate was 20.3% in patients who received chemotherapy and 20.4% in patients who did not receive chemotherapy (P = 0.96). CONCLUSIONS: The 5-year overall survival rate of stage IIIb adenocarcinoma of the uterine cervix in this retrospective questionnaire survey was 20.2%. The optimal T-BED(10) and evident prognostic factors were not clear from this questionnaire survey.

[Clinical practice guideline for lung cancer].

A clinical practice guideline for lung cancer in Japan was published by an expert multidisciplinary panel in 2003 and revised especially on the role of postoperative chemotherapy and the use of chemotherapeutic agents by the guideline committee of the Japan Lung Cancer Society in 2005. This guideline is divided into two parts as follows: 1) standard procedures for diagnostic techniques and treatment modalities such as surgery, chemotherapy and radiation therapy, the role of induction or adjuvant treatments for surgery and the approaches for central types of early bronchogenic cancer, and 2) standard adaptation of various methods of treatments according to the clinical stage. Now we are going to revise the guideline, renew the decision trees for standard treatment procedures and molecular targeted therapies based on the new TNM classification, and add parts to the treatments for malignant mesothelioma and the management of bone metastases with bisphosphonates.