IMRT using simultaneous integrated boost (66 Gy in 6 weeks) with and without concurrent chemotherapy in head and neck cancer – toxicity evaluation

AimTo evaluate the toxicity of intensity-modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) in head and neck cancer patients treated using a protocol comprising 66 Gy to the PTV1 (planning target volume; region of macroscopic tumour) and 60 Gy and 54 Gy to the regions with high risk (PTV2) and low risk (PTV3) of subclinical disease in 30 fractions in six weeks.Material and MethodsBetween December 2003 and February 2006, 48 patients (median age 55; range 25–83, performance status 0–1) with evaluable non-metastatic head and neck cancer of various localizations and stages (stages: I–1; II–8; III–12; IV–27 patients, resp.) were irradiated according to the protocol and followed (median follow-up 20 months; range 4–42). Ten patients underwent concurrent chemotherapy (CT) and in 15 patients the regimen was indicated postoperatively because of close or positive margins. In all cases the regimen was used as an alternative to conventional radiotherapy (70 Gy in 7 weeks). The acute and late toxicities were evaluated according to RTOG and RTOG/EORTC toxicity scales, respectively.ResultsAll patients finished the treatment without the need for interruption due to acute toxicity. No patient experienced grade 4 toxicity. More severe acute toxicity was observed in patients with CT, but the most severe toxicity was grade 3. Grade 3 toxicity was observed in the skin, mucous membrane, salivary glands, pharynx/oesophagus and larynx in 8.4%, 35.4%, 39.6% and 2.1%, in the CT subgroup in 10%, 100%, 90%, 10%, respectively. The trend of impairment of acute toxicity by concurrent chemotherapy was statistically confirmed by Fisher's exact test (for mucous membranes p=0.000002 and pharyngeal/oesophageal toxicity p=0.0004). The most severe late toxicity was grade 2 subcutaneous tissue (34.2%), mucous membrane (36.8%) and larynx (11.1%), grade 3 in salivary gland (2.6%) and grade 1 in skin (84.2%) and spinal cord (5.4%). The late toxicity was not increased by chemotherapy.ConclusionIn light of the toxicity profile we consider the presented regimen to be an alternative to conventional radiotherapy 70 Gy in 7 weeks. The addition of CT requires more intensive supportive care

Intesity modulated radiotherapy with simultanous integrated boost in the treatement of head and neck cancer.

Department of Oncology and RadiotherapyKlinika onkologie a radioterapieLékařská fakulta v Hradci KrálovéFaculty of Medicine in Hradec Králov

Is There Still a Place for Brachytherapy in the Modern Treatment of Early-Stage Oral Cancer?

Brachytherapy (BT) involves the direct application of radioactive sources to the tumour. This technique is characterised by a steep dose gradient, the delivery of high-dose radiation to the target volume centre, and the sparing of surrounding healthy tissues. Low-dose-rate (LDR) BT and manual afterloading played an important role in the treatment of early-stage oral cancer, with treatment outcomes that were comparable to surgery. Interest in BT as a primary treatment for oral cancer has declined in recent years due to the emergence of better surgical techniques, the switch from LDR BT to high-dose-rate (HDR) BT (which has a higher risk of complications), and to advances in external beam radiotherapy (EBRT). At present, the main indications for BT are in the postoperative setting due to the superior dose conformity and better quality of life offered by BT versus EBRT. Postoperative BT can be administered as monotherapy in early-stage (T1N0) cancers and in combination with elective neck dissection or EBRT to treat larger or deeper tumours. BT yields excellent results for lip carcinoma in older patients and in tumours with unfavourable localisations. BT is an effective salvage therapy for local recurrences in previously-irradiated areas. Despite its many advantages, brachytherapy is a complex treatment requiring meticulous technique and close cooperation between the radiation oncologist, physicist, and surgeon

Analysis of D1853N ATM Polymorphism in Radiosensitive Patients with Cervical Carcinoma

Clinical oncologists have been focusing their efforts on attempting to define risk groups of patients with unusual biological reactions to the recommended therapy regimens using molecular biology techniques. The aims of our study were: (i) to find a design and validate a method for fast and reliable analysis of the D1853N (5557G>A) genetic polymorphism in the ATM (ataxia-telangiectasia mutated) gene; (ii) to use side-directed mutagenesis to generate ATM 5557A-positive DNA (reference ATM5557A DNA); and (iii) to analyze a group of patients suffering from cervical carcinoma with adverse responses to radiotherapy. The 5557A variant was found in three of twenty women (15%). Our data show that the prevalence of the 5557A allelic variant in cervical cancer subjects with adverse responses after irradiation probably does not differ from the prevalence common in Caucasians. A larger population study should confirm these preliminary results

Cardiotoxicity of radiation therapy in esophageal cancer

With a development of radiotherapeutic techniques, availability of radiotherapy data on cardiotoxicity, and slowly improving esophageal cancer outcomes, an increasing emphasis is placed on the heart protection in radiation treated esophageal cancer patients. Radiation induced heart complications encompass mainly pericardial disease, cardiomyopathy, coronary artery atherosclerosis, valvular heart disease, and arrhythmias. The most frequent toxicity is pericardial effusion which is usually asymptomatic in the majority of patients. The use of modern radiotherapy techniques is expected to reduce the risk of cardiotoxicity, although this expectation has to be confirmed by clinical data

IMRT with the Use of Simultaneous Integrated Boost in Treatment of Head and Neck Cancer: Acute Toxicity Evaluation

Acute toxicity has been evaluated in head and neck cancer patients treated with intensity-modulated radiotherapy using simultaneous integrated boost (SIB-IMRT). The basis of the treatment protocol is an irradiation in 30 fractions with a total dose: 66 Gy to the region of macroscopic tumor, 60 Gy to the region of high-risk subclinical disease and 54 Gy to the region of low-risk subclinical disease. Between December 2003 and September 2005, 38 patients with carcinoma of different locations in the head and neck region were irradiated. Five patients underwent concurrent chemotherapy (weekly cisplatin). Acute toxicity was evaluated according to Radiation Therapy Oncology Group toxicity scale for skin, mucous membrane, salivary glands, pharynx and esophagus and larynx. All 38 patients completed the therapy without urgency of interruption due to acute toxicity of radiotherapy. No patient experienced grade 4 toxicity. More severe toxicity was observed in patients with concurrent chemotherapy. The results confirm that the irradiation according to our SIB-IMRT protocol is a therapy with acceptable toxicity and there is a space for radiobiological enhancement of this regimen by concurrent chemotherapy, e.g. weekly cisplatin

KONTROVERZE RADIOTERAPIE U PACIENTŮ S HIVDERMÁLNÍM RŮSTOVÝM FAKTOREM (HER)-2 POZITIVNÍCH PACIENTŮ S KARCINOMEM PRSU

Tumor biology plays a crucial role in the systemic treatment, specifically in HER2-positive tumors. Distinct biological behavior of breast cancer subtypes is associated with different rates of locoregional recurrence (LRR). HER2- positive breast cancer patients treated with surgery in combination with radiation, without trastuzumab have poor outcome, including high LRR. The efficacy of radiotherapy in HER-2-positive breast cancer appears to be associated with the expression of estrogen receptors. In patients with HER-2-positive breast cancer, studies conducted before the introduction of trastuzumab indicated higher benefit of adjuvant radiation in patients with hormone receptor-positive tumors compared to patients with tumors not expressing hormone receptors. The introduction of agents targeting HER-2 has transformed the management of these patients, resulting in improved outcomes. The data of clinical studies show that the administration of trastuzumab as part of a multimodality approach (with radiation based on standard guidelines) results in improved outcomes, including lower locoregional recurrence. The risk of cardiac toxicity associated with radiation to the heart and administration of potential cardiotoxic trastuzumab is not clear. In patients treated concomitantly with regional lymph node irradiation and anti-HER-2 agents after prior anthracycline-based chemotherapy minimizing the dose to the myocardium, e.g. respiratory gating or proton beam radiotherapy, have been suggested.Biologie nádorů hraje klíčovou roli v systémové léčbě, konkrétně v NÁDORECH POZITIVNÍCH NA HER2. Odlišné biologické chování podtypů rakoviny prsu je spojeno s různými mírami locoregionální recidivy (LRR). HER2- pozitivní pacienti s karcinomem prsu léčení chirurgicky v kombinaci s ozařováním, bez trastuzumabu mají špatný výsledek, včetně vysoké LRR. Účinnost radioterapie u HER-2 pozitivního karcinomu prsu se zdá být spojena s expresí estrogenních receptorů. U pacientů s HER- 2-pozitivním karcinomem prsu studie provedené před zavedením trastuzumabu ukázaly vyšší přínos adjuvans záření u pacientů s nádory pozitivními na hormonální receptory ve srovnání s pacienty s nádory, kteří nevyjadřují hormonální receptory. Zavedení látek zaměřených na HER-2 změnilo řízení těchto pacientů, což vedlo ke zlepšení výsledků. Údaje z klinických studií ukazují, že podávání trastuzumabu v rámci multimodality přístupu (s radiačním zářením založeným na standardních pokynech) vede ke zlepšení výsledků, včetně nižší locoregionální recidivy. Riziko srdeční toxicity spojené s ozářením srdce a podáním potenciálního kardiotoxické trastuzumabu není jasné. U pacientů léčených současně s ozářením regionálních lymfatických uzlin a anti-HER- 2 přípravky po předchozí chemoterapii na bázi antracyklinu, která minimalizovala dávku myokardu, např

Special Techniques of Adjuvant Breast Carcinoma Radiotherapy

Modern radiotherapy techniques are designed to permit reduced irradiation of healthy tissue, resulting in a diminished risk of adverse effects and shortened recovery times. Several randomized studies have demonstrated the benefits of increased dosage to the tumor bed area in combination with whole breast irradiation (WBI). Conventional WBI treatment following breast-conserving procedures, which required 5–7 weeks of daily treatments, has been reduced to 3–4 weeks when using hyperfractionated regimens. The dosage administration improves local control, albeit with poorer cosmesis. The method of accelerated partial breast irradiation (APBI) shortens the treatment period whilst reducing the irradiated volume. APBI can be delivered using intraoperative radiation, brachytherapy, or external beam radiotherapy. Currently available data support the use of external beam partial breast irradiation in selected patients. Modern radiotherapy techniques make it possible to achieve favorable cosmesis in most patients undergoing immediate breast reconstruction surgery, and studies confirm that current methods of external beam radiation allow an acceptable coverage of target volumes both in the reconstructed breast and in the regional lymphatic nodes

High-Dose-Rate Brachytherapy as an Organ-Sparing Treatment for Early Penile Cancer

Background: Low-dose-rate brachytherapy is an effective organ-sparing treatment for patients with early-stage penile cancer. However, only limited data are available on the role of high-dose-rate brachytherapy (HDR-BT) in this clinical setting. Methods: Between 2002 and 2020, 31 patients with early penile cancer were treated at our center with interstitial HDR BT at a dose of 18 × 3 Gy twice daily. A breast brachytherapy template was used for the fixation of stainless hollow needles. Results: The median follow-up was 117.5 months (range, 5–210). Eight patients (25.8%) developed a recurrence; of these, seven were salvaged by partial amputation. Six patients died of internal comorbidities or a second cancer. The probability of local control at 5 and 10 years was 80.7% (95% CI: 63.7–97.7%) and 68.3% (95% CI: 44.0–92.6%), respectively. Cause-specific survival was 100%. Only one case of radiation-induced necrosis was observed. The probability of penile sparing at 5 and 10 years was 80.6% (95% CI: 63.45–97.7%) and 62.1% (95% CI: 34.8–89.4%), respectively. Conclusions: These results show that HDR-BT for penile cancer can achieve results comparable to LDR-BT with organ sparing. Despite the relatively large patient cohort—the second largest reported to date in this clinical setting—prospective data from larger samples are needed to confirm the role of HDR-BT in penile cancer