Efficacy and Toxicity of Postoperative Temozolomide Radiochemotherapy in Malignant Glioma

Purpose: To evaluate the feasibility, safety and efficacy of daily temozolomide concurrent with postoperative radiotherapy in malignant glioma. Patients and Methods: From 11/1999 to 03/2003, n = 81 patients aged 15–72 years (median 52 years, Karnofsky score 80–100% in 83%) suffering from primary glioblastoma (n = 47), anaplastic astrocytoma (n = 6), anaplastic oligodendroglioma (n = 16), and recurrent glioma (n = 12) were treated. Patients with primary gliomas received a combination of postoperative radiotherapy (60 Gy/1.8- to 2.0-Gy fractions) and daily oral temozolomide (75 mg/m²) at all irradiation days (30–33 doses), while recurrent tumors were treated with 45–60 Gy and temozolomide. Initially, 6/81 patients had daily temozolomide doses of 50 mg/m². Results: In total, 70/81 patients (86%) completed both radio- and chemotherapy. Grade 1 nausea/vomiting was seen in 28%, grade 2 in 11%, grade 3 in 1%. Antiemetics were applied in 41%. Hematologic toxicities were observed as follows: leukopenia grade 3/4 1%, lymphopenia grade 3/4 46%, thrombopenia grade 3/4 1%. Two patients under dexamethasone suffered herpes encephalitis after one and 16 doses of temozolomide (75 mg/m²). Median survival was 15 months for glioblastoma. In oligodendroglioma patients, a 4-year survival rate of 78% was observed. Conclusion: Postoperative radiochemotherapy with 30–33 daily doses of temozolomide (75 mg/m²) is safe in patients with malignant glioma. The combined schedule is effective in oligodendroglioma patients and may prolong survival in glioblastoma. Effort should be taken to minimize corticosteroid doses, since both steroids and temozolomide lead to immunosuppression.     

Comparison of cisplatin and 5-fluorouracil chemotherapy protocols combined with concurrent radiotherapy for esophageal cancer

Purpose  The optimal chemotherapeutic protocol for the treatment of esophageal cancer has not yet been established. This study was performed to identify the differences in toxicity and completion rates of various chemotherapy protocols with that goal in mind. Materials and methods  A total of 61 patients with esophageal cancer were enrolled in this study between June 2002 and January 2004. The total radiotherapy dose was 64 Gy. Three chemotherapy protocols were used. Arm A comprised daily low-dose cisplatin (CDDP) and 5-fluorouracil (5FU) (CF protocol) (3 mg/m² and 180 mg/m², respectively). Arm B was intermediate between arm A and C (CDDP 7 mg/m² and 5FU 250 mg/m² on days 1–5, 8–12, 29–33, and 36–40). Arm C comprised two courses of standard CF (CDDP 70 mg/m² on day 1 and 5FU 600 mg/m²/24 h on days 1–4). Results  Although there were no significant differences in hematological toxicity between the protocols, leukocytopenia was slightly milder in arm A. Nausea was significantly more severe in arm C. The completion rate was higher in arm A. The 3-year survival rates were 40%, 31%, and 62%, respectively. Conclusion  The daily low-dose CF protocol showed a trend of mild toxicity regarding leukocytopenia. However, we could not find statistical difference between arms. It also showed a better completion rate than the other two arms.     

Chemoradiation therapy for cervical cancer: toxicity of concurrent weekly cisplatin

Purpose To retrospectively evaluate the toxicity of concurrent weekly cisplatin and radiation therapy (RT) for locally advanced cervical cancer. Materials and Methods Between April 2001 and December 2004, 21 consecutive previously untreated patients with locally advanced cervical cancer were treated with concurrent chemoradiation therapy (CCRT) at the Tokushima University Hospital. Clinical stages were II: 5, III: 15, IVA: 1. External beam radiation therapy (EBRT) was delivered with 10 MV X-rays, 2 Gy fraction per day; total dose to the whole pelvis was 50 Gy. Iridium-192 high-doserate (HDR) intracavitary radiation therapy was performed with 10–30 Gy (median, 24 Gy) targeted at point A. Concurrent chemotherapy consisted of cisplatin, administered weekly at a dose of 40 mg/m² for patients who were younger than 65 years and 30 mg/m² for those 65 years or over. A maximum single dose of cisplatin, up to 70 mg/body, was administered in 5 cycles during EBRT. Results A total of 86 cycles of cisplatin were administered to the 21 patients, with a median of 4 cycles (range, 2–5). Severe hematological toxicity occurred in 18 patients (86%), including grade 3 in 17 patients (81%) and grade 4 in one patient (4.8%). Moderate or severe gastrointestinal toxicity occurred in 11 patients (52%), including grade 2 in 10 patients (48%) and grade 3 in one patient (4.8%). The grades of hematological toxicity were significantly greater in the 40 mg/m² group than in the 30 mg/m² group. All of the patients who were administered 40 mg/m² of cisplatin developed grade 3 or greater hematological toxicity, including one patient with grade 4 toxicity. In the 30 mg/m² group, 3 of 10 patients developed less than grade 3 toxicity, and all patients completed radiation therapy without interruption. Conclusion The incidence of severe acute hematological toxicity was significantly higher in this study than in previously reported randomized controlled trials (RCTs), especially in the group of 40 mg/m² cisplatin. A dose of 30 mg/m² of cisplatin was considered to be feasible in weekly cisplatin and radiation therapy.     

局部晚期直肠癌术前同步放化疗中卡培他滨联合奥沙利铂剂量递增的I期临床研究

目的 探讨局部晚期直肠癌术前同步放化疗基于5-Fu类药物的联合方案中奥沙利铂的最大耐受剂量。方法 本试验设计为前瞻性研究,自2015年3月至2015年10月,入组经病理确诊的局部晚期（T₃、T₄/N+）直肠癌患者15例,接受调强放疗以及卡培他滨联合奥沙利铂方案的同步化疗。放疗采用同步局部加量, 总剂量GTV为50.6 Gy,CTV 41.8 Gy,共22次,30 d内完成。同期化疗,卡培他滨为固定剂量825 mg/m²,2次/d,每周1~5服用,伴随放疗全程;奥沙利铂剂量分别为100、110、120、130 mg/m²,共4个递增剂量水平组,每21天为1个周期。15例患者,前12例按随机数字表法分为4组,每组3例,最后一组因出现剂量限制性毒性又入组了3例患者,因此,第4组为6例。治疗后充分评估不良反应和有效率。结果 近期治疗相关不良反应主要表现为放射性肠炎、皮肤反应、恶心、乏力、泌尿系不良反应和骨髓抑制,并随奥沙利铂剂量的提高而增多、加重。观察100、110 和120 mg/m²组中未出现3级以上不良反应,130 mg/m²组中则出现了剂量限制性毒性：1例3级血小板减少和1例3级恶心,该剂量为最大耐受剂量。手术后病理显示,所有患者均达到降期,4组患者分别有0、1、2、3例达到完全缓解。结论 局部晚期直肠癌调强放疗同步联合卡培他滨及奥沙利铂方案安全有效。奥沙利铂的最大耐受剂量为130 mg/m²,1次/3周。     

Transcatheter Arterial Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres for Colorectal Liver Metastases after FOLFOX Failure: Results of a Phase I/II Study

PurposeTo report the results of a phase I/II study of a transcatheter arterial chemoembolization protocol using cisplatin powder and degradable starch microspheres (DSM) for unresectable colorectal liver metastases after failure of FOLFOX (5-flourouracil, leucovorin plus oxaliplatin) chemotherapy conducted to determine the recommended dose of cisplatin powder and to assess the efficacy and safety of the protocol.Materials and MethodsA fine-powder formulation of cisplatin was mixed with DSM and administered via the hepatic artery every 4 weeks. In phase I, three cohorts of patients received escalating doses of cisplatin powder: 50 mg/m², 65 mg/m², and 80 mg/m². In phase II, tumor response, toxicity, and survival times were assessed.ResultsThe study enrolled 24 patients. Previously, FOLFOX had been administered to all patients, an irinotecan-containing regimen had been administered to 12 patients, and bevacizumab or cetuximab or both had been administered to 14 patients. In phase I, dose-limiting toxicity did not appear at any level, and the recommended dose of cisplatin powder was determined to be 80 mg/m². In phase II, a tumor response rate of 61.1% was achieved. The median hepatic progression-free survival and overall survival were 8.8 months (95% confidence interval [CI], 4.06–13.5 mo) and 21.1 months (95% CI, 8.37–33.8 mo). The following grade 3 toxicities were observed: thrombocytopenia (12.5%), aspartate transaminase elevation (33.3%), alanine transaminase elevation (12.5%), hyponatremia (8.3%), and cholecystitis (4.2%).ConclusionsThis study shows that transcatheter arterial chemoembolization with cisplatin powder at a dose of 80 mg/m² mixed with DSM is well tolerated and can produce a high response rate with a long survival time for patients with unresectable colorectal liver metastases after failure of FOLFOX.     

吉西他滨诱导化疗后放疗同步联合卡培他滨治疗局部进展期胰腺癌的临床疗效

目的 评价吉西他滨诱导化疗后放疗同步联合卡培他滨治疗局部进展期胰腺癌（LAPC）的安全性及疗效。方法 对42例局部进展期胰腺癌用吉西他滨诱导化疗7周,每周1次,每次1000mg/m²,休息1周后开始放疗同步联合卡培他滨化疗,卡培他滨剂量为825mg/m²,2次/d,5d/周;放疗采用常规分割1.8~2.0Gy/次,中位照射剂量54Gy（34~64Gy）。结果 临床受益反应（CBR）20例,占47.6%;近期疗效：完全缓解（CR）2例,部分缓解（PR）8例,稳定（SD）27例,进展（PD）5例,中位生存时间10.1个月（4~36个月）;1年、2年生存率分别是38.2%和18.2%。骨髓抑制1~2级20例,3级以上5例;胃肠道不良反应1~2级22例,3级以上4例。结论 吉西他滨诱导化疗后再放化联合治疗局部进展期胰腺癌疗效较好,不良反应可耐受。     

Pre-targeted immunodetection in glioma patients: tumour localization and single-photon emission tomography imaging of [99mTc]PnAO-biotin

The imaging of cerebral gliomas with radiolabelled monoclonal antibodies (MoAbs) has been previously reported. However, previous studies have been hampered by the drawback of a low tumour to non-tumour ratio. In order to overcome this problem we have developed a three-step pre-targeting method using the avidin-biotin system. The rationale of this technique consists in vivo labelling of biotinylated MoAbs targeted onto tumour deposits, when most of the unbound antibodies have been cleared from the bloodstream as avidin-bound complexes. The anti-tenascin MoAb BC2, specific for the majority of gliomas, was biotinylated and 1 mg was administered i.v. in 20 patients with histologically documented cerebral lesions. After 24–36 h, 5 mg avidin was injected i.v. followed 24 h later by a third i.v. injection of 0.2 mg PnAO-biotin labelled with 15–20 tnCi technetium-99m. No evidence of toxicity was observed. Whole-body biodistribution was measured at 20 min, 3 h and 5 h post-injection. [^99mTc]PnAO-bio-tin had a fast blood clearance and was primarily excreted through the biliary system. A dedicated single-photon emission tomography system was used to acquire brain tomographic images 1–2 h after the administration of [^99mTc]PnAO-biotin. Tumours were detected in 15/18 glioma patients with a tumour to non-tumour ratio of up 14:1. This three-step method, based on the sequential administration of anti-tenascin MoAb BC2, avidin and [^99mTc]PnAO-biotin, can support computed tomography or magnetic resonance imaging for the diagnosis and follow-up of patients with glioma. Further studies are required to evaluate the potential of this technique for therapeutic application.     

化疗联合125I粒子治疗不能手术的肺上沟癌的疗效分析

目的 探讨应用放射治疗计划系统（TPS）在CT引导下经皮穿刺种植放射性¹²⁵I粒子近距离联合化疗治疗肺上沟癌的疗效分析。方法 回顾性分析2002年12月至2010年12月本院收治的影像及病理证实为肺上沟癌的患者36例,其中鳞癌26例,腺癌10例。粒子植入后1周行化疗,具体方案为第1、8天静脉给予1 000 mg/m²吉西他滨,第1天静脉给予顺铂75 mg/m²,连续4个周期。¹²⁵I粒子在化疗间期植入,中位粒子数43,处方剂量（prescribed dose,PD）120 Gy,粒子中位活度0.7 mCi （2.59×10⁷ Bq）,范围0.68~0.82 mCi （2.52×10⁷~3.03×10⁷ Bq）。患者中位随访时间48个月,观察生存率。结果 靶区瘤体周围处方剂量mPD （118.7±7.2）Gy,D₉₀（126±4.7）Gy,D₉₀> mPD。术后6个月胸部CT显示,完全缓解（CR）11例,占30.6%;部分缓解（PR）19例,占52.8%;疾病稳定（SD）5例,占13.9%;疾病进展（PD）1例,占2.8%;总有效率（CR＋PR）为83.4%,共30例。1、3、5年的局部控制率分别为92%、83%和67%,中位局部控制时间56.8个月。1、3、5年累计生存率分别为84.1%、56.7%和36.8%,中位生存期38个月。结论 化疗联合组织间近距离¹²⁵I粒子植入是一种微创有效的治疗肺上沟癌的方法。     

Phase I/II Study of Radiologic Hepatic Arterial Infusion of Fluorouracil Plus Systemic Irinotecan for Unresectable Hepatic Metastases from Colorectal Cancer: Japan Clinical Oncology Group Trial 0208-DI

PurposeTreatment of patients who have metastatic colorectal cancer (CRC) by using a combination of hepatic arterial infusion chemotherapy (HAIC) and systemic chemotherapy has resulted in promising clinical outcomes. Additionally, image-guided HAIC is reported to be less invasive and distribute drugs more accurately than surgical HAIC. The purpose of this study was to assess the combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan in a multicenter phase I/II study.Materials and MethodsTwenty-five patients with unresectable liver metastases from CRC were fitted with hepatic arterial catheter and port systems by using image-guided methods. Intraarterial fluorouracil (1,000 mg/m²) was administered on days 1, 8, and 15 of each treatment cycle. The dose of systemic irinotecan on days 1 and 15 was escalated from 75 mg/m².ResultsNo dose-limiting toxicity was encountered during phase I, and the recommended dose of irinotecan was set at 150 mg/m². Grade 3 or higher adverse events included hyperglycemia (15%), elevated γ-glutamyl transpeptidase levels (15%), and neutropenia (9%). The response rate and median survival time were 72% and 49.8 months (95% CI, 27.5–78.1 mo), respectively.ConclusionsThe combination of image-guided delivery of fluorouracil through HAIC and systemic irinotecan yielded favorable safety, response rate, and survival results. This combination should be evaluated in a large study.     

Two-step tumour targetting in ovarian cancer patients using biotinylated monoclonal antibodies and radioactive streptavidin

A new method for intraperitoneal tumour targetting in ovarian cancer using biotinylated monoclonal antibodies (MoAb) and radioactive streptavidin is described. Fifteen patients with histologically documented ovarian carcinoma were injected intraperitoneally with 2 mg of biotinylated MoAb MOv18, followed 3–5 days later by 100–150 g of indium-111 streptavidin, at the specific activity of 280–370 MBq/mg in 500 ml of normal saline. No toxicity was observed. Tumours were imaged from 2 to 48 h after radioactivity injection by recording both planar and single photon emission tomography (SPET) data. All patients underwent surgery 1–8 days later (mean 3 days) after scanning. The resected tumour and normal tissue radioactivity were measured. On the day of surgery, the tumour to normal tissue ratio was 9:1 (range 3:1–30:1) and 45:1 (range 12:1–120:1) for intra- and extraperitoneal samples, respectively. The mean tumor to blood ratio was 14:1 (range 4:1–30:1). The injected dose (i.d.) per gram of tumour was 0.112 (range 0.01–0.3) for recurrences and 0.05 for primary tumour (range 0.005–0.2). Over 24–48 h 14% i.d. (range 8–18% i.d.) was found in the urine, 14% i.d. (range 629% i.d.) in the blood and 63% i.d. (range 56–70% i.d.) was still in the peritoneal cavity. These preliminary clinical data suggest that this two-step strategy may be superior to the conventional approach (radiolabelled antibodies) for intraperitoneal radioimmunolocalization and radioimmunotherapy of ovarian cancer. Offprint requests to: G. Paganelli     

Feasibility of 6-month maintenance cetuximab after adjuvant concurrent chemoradiation plus cetuximab in squamous cell carcinoma of the head and neck

Background

Close resection margins <?5 mm (CM) or extra capsular extent at the lymph nodes (ECE) impair the prognosis of patients with squamous cell cancer of the head and neck (SCCHN) scheduled for adjuvant radiochemotherapy. We conducted a multicenter phase II study to investigate toxicity and efficacy of additional cetuximab administered concomitantly and as maintenance for the duration of 6 months following adjuvant radiochemotherapy., Ppreliminary results on feasibility and acute toxicity on skin and mucosa are presented in this article.

Methods

Patients with SCCHN following CM resection or with ECE were eligible for the study. In all, 61.6 Gy (1.8/2.0/2.2 Gy, days 1–36) were administered using an integrated boost intensity-modulated radiotherapy (IMRT) technique. Cisplatin (20 mg/m², days 1–5 and days 29–33) and 5-fluorouracil (5-FU) as continuous infusion (600 mg/m², days 1–5 + days 29–33) were given concurrently. Cetuximab was started 7 days prior to radiochemotherapy at 400 mg/m² followed by weekly doses of 250 mg/m². Maintenance cetuximab began after radiochemotherapy at 500 mg/m² every 2 weeks for 6 months.

Results

Of the 55 patients (46 male, 9 female, mean age 55.6, range 29–70 years) who finished radiochemotherapy, 50 were evaluable for acute toxicity concerning grade III/IV toxicities of skin and mucosa. Grade 3–4 (CTC 3.0) mucositis, radiation dermatitis, and skin reactions outside the radiation portals were documented for 46, 28, and 14?% of patients, respectively. One toxic death occurred (peritonitis at day 57). Cetuximab was terminated in 5 patients due to allergic reactions after the first application. In addition, 22?% of patients discontinued cetuximab within the last 2 weeks or at the end of radiochemotherapy. Of patients embarking on maintenance treatment, 80?% were still on cetuximab at 3 months and 63?% at 5 months. Concurrent and maintenance treatment with cetuximab could be administered as scheduled in 48?% of patients.

Conclusion

Adjuvant radiochemotherapy with concomitant and maintenance cetuximab is feasible and acute toxicities are within the expected range. Compliance within the first 3–5 months is moderate.     

Evaluation of the “Quadrella” at 3 years: New index to assess functional and oncological performance specific to prostate brachytherapy

Purpose“Quadrella” index has been recently developed to assess oncological and functional outcomes after prostate brachytherapy (PB). We aimed to evaluate this index at 1, 2, and 3 years, using validated questionnaires, assessed prospectively.Methods and MaterialsFrom 08/2007 to 01/2013, 193 patients underwent ¹²⁵Iodine PB for low-risk or favorable intermediate-risk prostate adenocarcinoma. Inclusion criteria were as follows: no incontinence (International Continence Society Index initial score = 0) and good erectile function (International Index of Erectile Function–5 items: >16). One hundred patients were included (mean age: 64 y). Postimplantation intake of phosphodiesterase inhibitors was not considered as failure. The “Quadrella” index was defined by the absence of biochemical recurrence (Phoenix criteria), significant erectile dysfunction (ED) (Index of Erectile Function–5 items: >16), urinary toxicity (UT) (International Prostate Score Symptom [IPSS] <15 or IPSS> 15 with ΔIPSS <5), and rectal toxicity (RT) (Radiation Therapy Oncology Group = 0).ResultsAt 12 months, 90 patients were evaluable: 42/90 (46.7%) achieved Quadrella. The main criteria for failure were as follows: ED in 77.1% (37/48) of cases, RT in 20.8% (10/48) of cases, and UT in 12.5% (9/57) of cases. At 24 and 36 months, 59.3% (48/81) and 61.1% (44/72) of patients achieved Quadrella, respectively. The main cause of failure was ED in 69.7% (23/33) and 85.7% (24/28) of cases, while RT was involved in 21.2% (7/33) and in 3.6% (1/28) of cases, and UT in 9.1% (3/33) and 3.6% (1/28) of cases. Only one case of biochemical recurrence was observed (i.e., 1/28 = 3.6% at 3 y).ConclusionsThe Quadrella can be used at 1, 2, and 3 years after PB. It allows to take into account the urinary and RT specific to PB. ED was the main cause of failure. This index will be useful to assess midterm and long-term results.     

Weekly gemcitabine and cisplatin concurrent with pelvic irradiation for primary therapy of cervical cancer: report of the first seven cases in Thai women

Purpose The aim of this study was to evaluate the compliance, response, and side effects of weekly gemcitabine (125 mg/m²) given concomitantly with standard weekly cisplatin (40 mg/m²) and pelvic radiotherapy for primary treatment of cervical cancer stage IB2–IVA in the first seven Thai cases. Materials and methods Weekly gemcitabine at a dose of 125 mg/m² was given concomitantly with cisplatin at 40 mg/m² for six cycles with concurrent radiotherapy in primary therapy of stage IB2–IVA cervical cancer. Radiation consisted of 5000 cGy in 25 daily fractions combined with brachytherapy to take point A to about 8600 cGy. Results Using weekly gemcitabine at a dose of 125 mg/m² with cisplatin at a dose of 40 mg/m², five of seven patients demonstrated a dose-limiting toxicity (DLT). DLTs consisted of nephrotoxicity in three cases and bone marrow suppression in two cases. Only one of seven patients could go through six cycles. All 5 living patients had a clinically complete response. Conclusions Weekly gemcitabine at a dose of 125 mg/m² with cisplatin at a dose of 40 mg/m² given concurrently with primary pelvic radiotherapy resulted in an excellent response but unacceptable toxicities for Thai women. The trial protocol was changed by reducing the cisplatin dosage to 20 mg/m².     

Simultaneous neoadjuvant radiochemotherapy with capecitabine and oxaliplatin for locally advanced rectal cancer

Background

Phase II trials of neoadjuvant treatment in UICC-TNM stage?II and III rectal cancer with capecitabine and oxaliplatin demonstrated favourable rates on tumour regression with acceptable toxicity.

Patients and methods

Retrospective evaluation of 34 patients treated from 2005–2008 outside clinical trials (CTR) with neoadjuvant irradiation (45–50.4?Gy) and simultaneous capecitabine 825?mg/m² b.i.d. on days 1–14 and 22–35 and oxaliplatin 50?mg/m² on days 1, 8, 22 and 29 (CAPOX). Twenty-six (77%) patients received one or two courses of capecitabine 1,000?mg/m² b.i.d. on days 1–14 and oxaliplatin 130?mg/m² on day 1 (XELOX) prior to simultaneous chemoradiotherapy.

Results

UICC-TNM stage regression was observed in 60% (n?=?20). Dworak’s regression grades 3 and 4 were achieved in 18.2% (n?=?6) and 15.1% (n?=?5) of the patients. Sphincter-preserving surgery was performed in 53% (n?=?8) of patients with a tumour of the lower rectum. Within the mean observation of 24 months, none of the patients relapsed locally, 1?patient had progressive disease and 5?patients (15%) relapsed distantly. Toxicity of grade 3 and 4 was mainly diarrhoea 18% (n?=?6) and perianal pain 9% (n?=?3). Nevertheless, severe cardiac events (n?=?2), severe electrolyte disturbances (n?=?2), and syncopes (n?=?2) were observed as well.

Conclusion

Treatment efficacy and common toxicity are similar to the reports of phase?I/II trials. However, several severe adverse events were observed in our cohort study. The predisposing factors for these events have yet to be studied and may have implications for the selection of patients outside CTR.     

Induction chemotherapy followed by simultaneous hyperfractionated radiochemotherapy in advanced head and neck cancer

Purpose

To evaluate the feasibility of induction chemotherapy followed by concomitant chemotherapy and hyperfractionated irradiation in locally advanced, inoperable head and neck cancer.

Methods

A pilot study was undertaken comprising 3 cycles of cisplatinum (100 mg/m², day 1) and 5-fluorouracil (1000 mg/m² in continuous intravenous infusion over the first 120 h) followed by bifractionated radiotherapy applied to tumor/involved lymph nodes up to the dose of 74.4 Gy given in 2 fractions of 1.2 Gy daily for 5 days a week combined with concomitant weekly cisplatinum infusion (50 mg/m²).

Results

Six patients were enrolled in the study. All of them completed the protocol therapy. Severe mucositis and myelotoxicity were the most common acute side effects observed in all and in 5 of the patients, respectively. Acute toxicity required interruption of concomitant chemotherapy in 5 cases and in 2 interruption of radiotherapy was necessary. Opioid analgesic parenteral therapy was administered in 4 patients. Three of them had to be hospitalized. One patient experienced cerebral stroke 1 day after the completion of therapy and died 7 days later. Due to high acute toxicity, patient accrual was terminated after 6 patients. At the mean follow-up of 17 months, 4 patients are alive, 3 of them are free of disease and in 1 local progression has been diagnosed.

Conclusions

High acute toxicity of induction cisplatinum and 5-fluorouracil followed by concomitant cisplatinum and hyperfractionated irradiation calls for less toxic treatment schedules in locally advanced inoperable head and neck cancer.     

Prostate hypofractionated radiotherapy (62Gy at 3.1Gy per fraction) with injection of hyaluronic acid: final results of the RPAH1 study

Objectives:The present multicenter Phase II study evaluated the rate of late grade ≥2 gastrointestinal (GI) toxicities at 3 years, after hypofractionated radiotherapy (HFR) of prostate cancer with injection of hyaluronic acid (HA) between the prostate and the rectum.Methods:Between 2010 and 2013, 36 patients with low- or intermediate-risk prostate cancer were treated by HFR/IMRT-IGRT. 20 fractions of 3.1 Gy were delivered, 5 days per week for a total dose of 62 Gy. A transperineal injection of 10cc of HA was performed between the rectum and the prostate. Late toxicities were evaluated between 3 and 36 months after the end of treatment (CTCAE v4).Results:Median pretreatment prostate-specific antigen was 8 ng ml⁻¹. Among the 36 included patients, 2 were not evaluated because they withdrew the study in the first 3 months of follow-up, and 4 withdrew between 3 and 36 months, the per protocol population was therefore composed.Late grade ≥2 GI toxicities occurred in 4 (12%) patients with 3 (9%) Grade 2 rectal bleedings and one diarrhoea. Therefore, the inefficacy hypothesis following Fleming one-stage design cannot be rejected. None of the patients experienced late Grade 3–4 toxicities. Among the 30 patients completing the 36 months’ visit, none still had a grade ≥2 GI toxicity. Late grade ≥2 genitourinary (GU) toxicities occurred in 14 (41%) patients. The most frequent toxicities were dysuria and pollakiuria. Four patients still experienced a grade ≥2 GU toxicity at 36 months.The biochemical relapse rate (nadir +2 ng ml⁻¹) was 6% (2 patients). Overall, HA was very well tolerated with no pain or discomfort.Conclusion:Despite the inefficacy of HA injection was not rejected, we observed the absence of Grade 3 or 4 rectal toxicity as well as a rate of Grade 2 rectal bleeding below 10% at 36 months of follow-up. Late urinary toxicities are the most frequent but the rate decreases largely at 3 years.Advances in knowledge:With an injection of HA, hypofractionated irradiation in 4 weeks is well tolerated with no Grade 3 or 4 GI toxicity and a rate of Grade 2 rectal bleeding below 10% at 36 months of follow-up.     

Technetium-99m antimyosin antibody (3–48) myocardial imaging: human biodistribution,safety and clinical results in detection of acute myocardial infarction

Technetium-99m antimyosin (^99mTc-AM) antibody imaging may have significant advantages over indium-111 antimyosin in clinical practice. The purpose of this study was to determine the human biodistribution, the safety profile and the sensitivity of^99mTc-AM (3–48) imaging in the detection of both Q-wave and non-Q-wave myocardial infarction (MI). Biodistribution and safety parameters were mainly determined in 12 normal healthy volunteers while 40 patients with proven MI (22 Q-wave, 18 non-Q-wave) were injected with^99mTc-AM (20–25 mCi) between 5 h and 7 days after the onset of acute chest pain. Three standard planar views were performed at 6 h and at 24 h post injection. Both sets of images were completed in 33 patients while two patients were imaged only at 6 h, three patients only at 18 h and one at 18 and 24 h. One patient was not imaged. Vital signs and ECG were recorded and blood samples for haematology, biochemistry and human antimurine antibodies (HAMA) and urinalysis were obtained in all volunteers and patients. No serious adverse reactions or side-effects attributable to^99mTc-AM have been reported. No volunteers or patients developed allergic reactions or significant increases in HAMA titres. Reading of^99mTc-AM imaging was performed by two blinded experienced observers. The sensitivity of^99mTc-AM in the detection of MI was 100% (21/21) for Q-wave and 83.3% (15/18) for non-Q-wave infarctions. The overall sensitivity was 92.3% (36/39). The three false-negative cases were inferoposterior MI. A certain degree of uptake focalization was seen in 26 out of 35 (74.2%) at 6 h. At 24 h, two patients (5.8%) did not show^99mTc-AM uptake while 22 (64.7%) showed intense focal uptake, seven (20.6%) moderate uptake and 3 (8.9%) slight uptake. It is concluded that^99mTc-AM (3–48) imaging is safe and shows high sensitivity in the detection of both Q-wave and non-Q-wave MI even with early imaging (6 h post injection). These promising results warrant further clinical investigation.     

Srinagarind Hospital experience in concurrent chemoradiation for 100 patients with stage IB2 to IVA uterine cervical cancer

Purpose The aim of this study was to determine responses, acute adverse effects, and survival outcomes of women with stage IB2 to IVA treated with weekly cisplatin concurrent with pelvic irradiation at Srinagarind Hospital. Materials and methods The medical records of 100 women with cervical cancer stage IB2 to IVA who were treated with weekly cisplatin 40 mg/m² concurrent with pelvic radiotherapy at Srinagarind Hospital between January 2003 and June 2006 were reviewed and analyzed. Results During the study period, 100 women were eligible for analysis, with a mean age of 46 years (range 24–60 years). Distribution according to International Federation of Gynecology and Obstetrics (FIGO) staging was IB2 1.0%, IIB 47.0%, IIIB 51.0%, and IVA 1.0%, respectively. A total of 86 patients received five or more cycles of weekly cisplatin. Grade 3 and 4 hematologic toxicities were found in 6.0%. The overall response rate was 97.0%. Complete response was achieved in 86 patients (86.0%) and partial response in 11 patients (11.0%). Stable disease was found in 1 patient (1.0%) but no progressive disease was found. Progression-free survival and overall survival rate were 69.6% and 96.1%, respectively. Conclusion Weekly cisplatin (40 mg/m²) concurrent with pelvic irradiation for locally advanced cervical cancer was effective with acceptable toxicity in Thai women.     

<Superscript>99m</Superscript>Tc-EDDA/HYNIC-TOC and <Superscript>18</Superscript>F-FDG in thyroid cancer patients with negative <Superscript>131</Superscript>I whole-body scans

Several studies have reported on the expression of somatostatin receptors in patients with differentiated thyroid cancer (DTC). The aim of this study was to evaluate the imaging abilities of a recently developed technetium-99m labelled somatostatin analogue, ^99mTc-EDDA/HYNIC-TOC (^99mTc-TOC), in terms of precise localisation of disease. The study population comprised 54 patients (24 men, 30 women; age range 22–90 years) with histologically confirmed DTC who presented with recurrent or persistent disease as indicated by elevated Tg levels after initial treatment. All patients were negative on the iodine-131 post-therapy whole-body scans. Fluorine-18 fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) was performed in a subgroup of 36 patients. The study population consisted of two groups: Group A (n=22) comprised patients with disease recurrence as shown by elevated Tg levels but without detectable pathology. In group B (n=32), pre-existing lesions were known. Among the 54 cases, SSTR scintigraphy was true positive in 33 (61.1%), true negative in 4 (7.4%) and false negative in 17 (31.5%) cases, which resulted in a sensitivity of 66%. A total of 138 tumour foci were localised in 33 patients. The fraction of true positive ^99mTc-TOC findings was positively correlated (P<0.01) with elevated Tg levels (higher than 30 ng/ml). Despite two false positive findings, analysis on a lesion basis demonstrated better diagnostic efficacy with ¹⁸F-FDG PET (P<0.001); however, it also revealed substantial agreement between the imaging techniques [Cohens kappa of 0.62 (0.47–0.78)]. In conclusion, scintigraphy with ^99mTc-TOC might be a promising tool for treatment planning; it is easy to perform and showed sufficient accuracy for localisation diagnostics in thyroid cancer patients with recurrent or metastatic disease.     

Low-dose fractionated radiotherapy and concomitant chemotherapy for recurrent or progressive glioblastoma

Backgroud

Evaluated in this study were the feasibility and the efficacy of concurrent low dose fractionated radiotherapy (LD-FRT) and chemotherapy as palliative treatment for recurrent/progressive glioblastoma multiforme (GBM).

Patients and methods

Eligible patients had recurrent or progressive GBM, Karnofsky performance status ≥?70, prior surgery, and standard radiochemotherapy treatment. Recurrence/progression disease during temozolomide (TMZ) received cisplatin (CDDP; 30 mg/m² on days 1, 8, 15), fotemustine (FTM; 40 mg/m² on days 2, 9, 16), and concurrent LD-FRT (0.3 Gy twice daily); recurrence/progression after 4 months from the end of adjuvant TMZ were treated by TMZ (150/200 mg/m² on days 1–5) concomitant with LD-FRT (0.4 Gy twice daily). Primary endpoints were safety and toxicity.

Results

A total of 32 patients were enrolled. Hematologic toxicity G1–2 was observed in 18.7?% of patients and G3–4 in 9.4?%. One patient (3.1?%) had complete response, 3 (9.4?%) had partial response, 8 (25?%) had stable disease for at least 8 weeks, while 20 patients (62.5?%) experienced progressive disease. The clinical benefit was 37.5?%. Median progression-free survival (PFS) and overall survival (OS) were 5 and 8 months, respectively. Survival rate at 12 months was of 27.8?%.

Conclusion

LD-FRT and chemotherapy for recurrent/progressive GBM have a good toxicity profile and clinical outcomes, even though further investigation of this novel palliative treatment approach is warranted.