Terms Of Tumor Control Research Articles

Treatment of acromegaly patients with risk-adapted single or fractionated stereotactic high-precision radiotherapy

The purpose of this work was to evaluate a prospectively initiated two-center protocol of risk-adapted stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) in patients with acromegaly. In total 35 patients (16 men/19 women, mean age 54 years) were prospectively included in a treatment protocol of SRS [planning target volume (PTV < 4 ccm, > 2 mm to optic pathways = low risk] or SRT (PTV ≥ 4 ccm, ≤ 2 mm to optic pathways = high risk). The mean tumor volume was 3.71 ccm (range: 0.11-22.10 ccm). Based on the protocol guidelines, 21 patients were treated with SRS and 12 patients with SRT, 2 patients received both consecutively. The median follow-up (FU) reached 8 years with a 5-year overall survival (OS) of 87.3% [confidence interval (CI): 70.8-95.6%] and 5-year local control rate of 97.1% (CI: 83.4-99.8%). Almost 80% (28/35) presented tumor shrinkage during FU. Endocrinological cure was achieved in 23% and IGF-1 normalization with reduced medication was achieved in 40% of all patients. An endocrinological response was generally achieved within the first 3 years, but endocrinological cure can require more than 8 years. A new adrenocorticotropic hypopituitarism occurred in 13 patients (46.4%). A new visual field disorder and a new oculomotor palsy occurred in 1 patient, respectively. Patients with occurrence of visual/neurological impairments had a longer FU (p = 0.049). Our SRS/SRT protocol proved to be safe and successful in terms of tumor control and protection of the visual system. The timing and rate of endocrine improvements are difficult to predict. One has to accept an unavoidable rate of additional adrenocorticotropic hypopituitarism in the long term.

Intra-arterial chemotherapy for retinoblastoma: First Indian report.

Aim:To describe treatment outcomes and complications of selective intra-arterial chemotherapy (IAC) for retinoblastoma (RB) in Indian eyes.Materials and Methods:Single center, retrospective interventional case series of 6 eyes with RB who underwent IAC using Melphalan (3 mg/5 mg/7.5 mg) and topetecan (1 mg) (n = 4) or melphalan (3 mg/5 mg/7.5 mg) alone (n = 2) between December 2013 and June 2014. In all, 17 IAC procedures were performed using selective ophthalmic artery cannulation. Treatment outcomes were evaluated in terms of tumor control, vitreous and subretinal seeds control and globe salvage rates.Results:IAC was employed as primary (n = 1) or secondary (n = 5) modality of treatment. Each eye received mean 3 IAC sessions (median: 3; range: 1-4 sessions). Eyes were classified according to international classification of RB as Group B (n = 1), C (n = 1), D (n = 2) and E (n = 2). Following IAC, complete regression of the main tumor was seen in 3 cases (50%), partial regression in 2 (33%), while 1 case (15%) showed no response. Of 4 eyes with subretinal seeds, 1 (25%) eye had complete regression while 3 (75%) eyes had partial regression. Of 5 eyes with vitreous seeds, 2 (40%) eyes had complete regression while 3 (60%) eyes had a partial response. Globe salvage was achieved in 5 of 6 eyes (83%). Diffuse choroidal atrophy and vitreous hemorrhage were observed in 1 (17%) eye, each. No hematologic toxicity or cerebro-vascular events were observed. Mean follow-up period was 5.5 months (median: 6 months, range: 1-6 months).Conclusion:IAC is an effective therapy for globe preservation in eyes with RB. Larger studies with longer follow-up are required to validate these results.

Gamma Knife radiosurgery for vestibular schwannoma: clinical results at long-term follow-up in a series of 379 patients.

Since the 1990 s, Gamma Knife radiosurgery (GKRS) has become the first-line treatment option for small- to medium-size vestibular schwannomas (VSs), especially in patients without mass effect-related symptoms and with functional hearing. The aim of this study was to assess the safety and efficacy of GKRS, in terms of tumor control, hearing preservation, and complications, in a series of 379 consecutive patients treated for VS. Of 523 patients treated at the authors' institution for VS between 2001 and 2010, the authors included 379 who underwent GKRS as the primary treatment. These patients were not affected by Type 2 neurofibromatosis and had clinical follow-up of at least 36 months. Clinical follow-up (mean and median 75.7 and 69.5 months, respectively) was performed for all patients, whereas audiometric and quantitative radiological follow-up examinations were obtained for only 153 and 219 patients, respectively. The patients' ages ranged from 23 to 85 years (mean 59 years). The mean tumor volume was 1.94 ± 2.2 cm(3) (median 1.2 cm(3), range 0.013-14.3 cm(3)), and the median margin dose was 13 Gy (range 11-15 Gy). Parameters considered as determinants of the clinical outcome were long-term tumor control, hearing preservation, and complications. A statistical analysis was performed to correlate clinical outcomes with the radiological features of the tumor, dose-planning parameters, and patient characteristics. Control of the tumor with GKRS was achieved in 97.1% of the patients. In 82.7% of the patients, the tumor volume had decreased at the last follow-up, with a mean relative reduction of 34.1%. The rate of complications was very low, with most consisting of a transient worsening of preexisting symptoms. Patients who had vertigo, balance disorders, or facial or trigeminal impairment usually experienced a complete or at least significant symptom relief after treatment. However, no significant improvement was observed in patients previously reporting tinnitus. The overall rate of preservation of functional hearing at the long-term follow-up was 49%; in patients with hearing classified as Gardner-Robertson (GR) Class I, this value was 71% and reached 93% among cases of GR Class I hearing in patients younger than 55 years. Gamma Knife radiosurgery is a safe and effective treatment for VS, achieving tumor control in 97.1% of cases and resulting in a very low morbidity rate. Younger GR Class I patients had a significantly higher probability of retaining functional hearing even at the 10-year follow-up; for this reason, the time between symptom onset, diagnosis, and treatment should be shortened to achieve better outcomes in functional hearing preservation.

Clinical review: Functioning gonadotroph adenomas.

Functioning gonadotroph adenomas (FGAs) are pituitary tumors secreting biologically active gonadotropins. The published literature includes only small case series or individual case reports. This review summarizes the published data on this rare entity and, based on them, suggests guidance on the follow-up of these patients. A review of articles in English retrieved from the PubMed up to December 2013 was conducted. The following terms were used for the search: "functioning gonadotroph adenomas," "FSH secreting adenomas," "LH secreting adenomas," "gonadotroph adenomas," "ovarian hyperstimulation," "macroorchidism," "testicular enlargement," and "precocious puberty." All reported cases of FGA were assessed, and information on presenting manifestations, management approaches, and long-term outcome was reviewed. FGAs cause distinct manifestations and, based on the limited published literature, they are mostly macroadenomas. Their pathogenesis remains enigmatic. Systematic series on their optimal management are lacking, but the primary therapy remains surgical excision of the adenoma. Given the risk of recurrence, long-term clinical and imaging follow-up is needed, and radiotherapy may be required. There is little evidence that medical therapies are particularly helpful, certainly in terms of tumor control. Central registration would enhance our insight regarding their pathology and optimal management.

VATE: VAlidation of high TEchnology based on large database analysis by learning machine

SUMMARY The interaction between implementation of new technologies and different outcomes can allow a broad range of researches to be expanded. The purpose of this paper is to introduce the VAlidation of high TEchnology based on large database analysis by learning machine (VATE) project that aims to combine new technologies with outcomes related to rectal cancer in terms of tumor control and normal tissue sparing. Using automated computer bots and the knowledge for screening data it is possible to identify the factors that can mostly influence those outcomes. Population-based observational studies resulting from the linkage of different datasets will be conducted in order to develop predictive models that allow physicians to share decision with patients into a wider concept of tailored treatment.

Re-evaluating the Optimal Radiation Dose for Definitive Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

The optimal radiation dose for treating esophageal squamous cell carcinoma (ESCC) has long been debated. We evaluated if doses greater than 50.4 Gy delivered with modern techniques are beneficial in terms of tumor control, survival, and toxicity. We included 193 consecutive patients with ESCC treated with definitive concurrent chemoradiotherapy from 1998 to 2012. Patients were treated to a dose of ≤50.4 Gy (low-dose, n = 137) or greater than 50.4 Gy (high-dose, n = 56). Tumor response, local-regional control, survival, and treatment toxicity were compared between groups. High-dose group had a significantly lower local failure rate (17.9% versus 34.3%, p = 0.024) and a marginal better 5-year local-regional failure-free survival (68.7% versus 55.9%, p = 0.052) than the low-dose group. No significant differences were found between high- and low-dose groups in tumor complete response rate (p = 0.975), regional failure rate (p = 0.336), distant metastasis rate (p = 0.390), or 5-year overall survival (p = 0.617). No difference in the incidence of toxic effects was observed between the two groups except for grade 3 skin reaction (12.5% [high] versus 2.2% [low], p < 0.001) and grade greater than or equal to 3 esophageal stricture (32.1% [high] versus 18.2% [low], p = 0.037). Local tumor control might be improved by higher dose of greater than 50.4 Gy, when delivered with modern techniques and concurrent chemotherapy, at the consequence of increased toxicity without impact on overall survival.

Frontiers in radiotherapy for early-stage invasive breast cancer.

The development of breast-conserving treatment for early-stage breast cancer is one of the most important success stories in radiation oncology in the latter half of the twentieth century. Lumpectomy followed by radiotherapy provides an appealing alternative to mastectomy for many women. In recent years, there has been a shift in clinical investigational focus toward refinements in the methods of delivering adjuvant radiotherapy that provide shorter, more convenient schedules of external-beam radiotherapy and interstitial treatment. Expedited courses of whole-breast treatment have been demonstrated to be equivalent to traditional lengthier courses in terms of tumor control and cosmetic outcome and to provide an opportunity for cost efficiencies.

Risk-adapted single or fractionated stereotactic high-precision radiotherapy in a pooled series of nonfunctioning pituitary adenomas: high local control and low toxicity.

PurposeThe purpose of this work was to evaluate a prospectively initiated two-center protocol of risk-adapted single-fraction (SRS) or fractionated radiotherapy (SRT) in patients with nonsecretory pituitary adenomas (NSA).Patients and methodsA total of 73 NSA patients (39 men/34 women) with a median age of 62 years were prospectively included in a treatment protocol of SRS [planning target volume (PTV) < 4 ccm, > 2 mm to optic pathways = low risk] or SRT (PTV ≥ 4 ccm, ≤ 2 mm to optic pathways = high risk) in two Novalis® centers. Mean tumor volume was 7.02 ccm (range 0.58–57.29 ccm). Based on the protocol guidelines, 5 patients were treated with SRS and 68 patients with SRT.ResultsMedian follow-up (FU) reached 5 years with 5-year overall survival (OS) of 90.4 % (CI 80.2–95 %) and 5-year local control and progression-free survival rates of 100 % (CI 93.3–100 %) and 90.4 % (CI 80.2–95 %), respectively. A post-SRS/SRT new visual disorder occurred in 2 patients (2.7 %), a new oculomotor nerve palsy in one pre-irradiated patient, in 3 patients (4.1 %) a pre-existing visual disorder improved. New complete hypopituitarism occurred in 4 patients (13.8 %) and in 3 patients (25 %) with pre-existing partial hypopituitarism. Pituitary function in 26 % of patients retained normal. Patients with tumor shrinkage (65.75 %) had a significantly longer FU (p = 0.0093). Multivariate analysis confirmed correlation of new hypopituitarism with duration of FU (p = 0.008) and correlation of new hypopituitarism and tumor volume (p = 0.023). No significant influence factors for occurrence of visual disorders were found.ConclusionOur SRS/SRT protocol proved to be safe and successful in terms of tumor control and protection of the visual system, especially for large tumors located close to optic pathways.

Conventional 2D (2DRT) and 3D conformal radiotherapy (3DCRT) versus intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer treatment

Nasopharyngeal carcinoma represents a distinct entity as compared to other head and neck tumours. Radio-chemotherapy is the treatment of first choice in non-metastatic disease. Intensity-modulated radiation therapy (IMRT) allows the sparing of parotid glands, improving the toxicity profile. The aim of this study was to compare the results obtained with IMRT with those obtained with conventional 2D (2DRT) and 3D conformal radiation therapy (3DCRT) in terms of tumour control, survival, acute and late toxicity. We reviewed the clinical records of 52 patients with histologically proven carcinoma of the nasopharynx (stage I-IVB according to the 2002 American Joint Committee on Cancer staging system) treated with curative intent between January 2003 and August 2011: 26 patients were treated with 2D or 3D technique (arm A) and 26 with IMRT technique (arm B) with simultaneous integrated boost. Fifty patients (96 %) received chemotherapy. Local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), acute and late toxicity were retrospectively evaluated. After a median follow-up of 37.6 months (69 months in arm A and 23 months in arm B), 69 % of patients were alive and disease-free, 10 % were alive with disease and 21 % died of disease, with an OS of 81 % at 2 years and 79 % at 5 years, a LC rate of 88 % at 2 years and 78 % at 5 years, a LRC rate of 80 % at 2 years and 73 % at 5 years and a DFS of 74 % at 2 years and 65 % at 5 years, with no statistically significant differences between IMRT and 2DRT/3DCRT. In multivariate analysis, the TNM stage and the volume treated at high dose correlated with DFS. No factor was found to be related to OS. Chronic toxicity was not statistically different in the two study groups and in particular ≥ G2 xerostomia rates were 67 and 41 % in arm A and B, respectively (p = 0.10). The findings of this study confirm that IMRT associated with chemotherapy, even with moderately hypofractionated regimens, allows good disease control with better results in terms of late xerostomia, although without statistically significant differences compared to 2DRT and 3DCRT. The hypothesis of an impact of IMRT on survival has yet to be confirmed.

Radiobiologic comparison of helical tomotherapy, intensity modulated radiotherapy, and conformal radiotherapy in treating lung cancer accounting for secondary malignancy risks

The aim of the present study is to examine the importance of using measures to predict the risk of inducing secondary malignancies in association with the clinical effectiveness of treatment plans in terms of tumor control and normal tissue complication probabilities. This is achieved by using radiobiologic parameters and measures, which may provide a closer association between clinical outcome and treatment delivery. Overall, 4 patients having been treated for lung cancer were examined. For each of them, 3 treatment plans were developed based on the helical tomotherapy (HT), multileaf collimator-based intensity modulated radiation therapy (IMRT), and 3-dimensional conformal radiation therapy (CRT) modalities. The different plans were evaluated using the complication-free tumor control probability (p+), the overall probability of injury (pI), the overall probability of control/benefit (pB), and the biologically effective uniform dose (D¯¯). These radiobiologic measures were used to develop dose-response curves (p-D¯¯ diagram), which can help to evaluate different treatment plans when used in conjunction with standard dosimetric criteria. The risks for secondary malignancies in the heart and the contralateral lung were calculated for the 3 radiation modalities based on the corresponding dose-volume histograms (DVHs) of each patient. Regarding the overall evaluation of the different radiation modalities based on the p+ index, the average values of the HT, IMRT, and CRT are 67.3%, 61.2%, and 68.2%, respectively. The corresponding average values of pB are 75.6%, 70.5%, and 71.0%, respectively, whereas the average values of pI are 8.3%, 9.3%, and 2.8%, respectively. Among the organs at risk (OARs), lungs show the highest probabilities for complications, which are 7.1%, 8.0%, and 1.3% for the HT, IMRT, and CRT modalities, respectively. Similarly, the biologically effective prescription doses (DB¯¯) for the HT, IMRT, and CRT modalities are 64.0, 60.9, and 60.8Gy, respectively. Regarding the risk for secondary cancer, for the heart, the lowest average risk is produced by IMRT (0.10%) compared with the HT (0.17%) and CRT (0.12%) modalities, whereas the 3 radiation modalities show almost equivalent results regarding the contralateral lung (0.8% for HT, 0.9% for IMRT, and 0.9% for CRT). The use of radiobiologic parameters in the evaluation of different treatment plans and estimation of their expected clinical outcome is shown to provide very useful clinical information. The radiobiologic analysis of the response probabilities showed that different radiation modalities appear to be more effective in different patient geometries and target sizes and locations. Furthermore, there is not a clear pattern between the plans that appear to be more effective for the treatment and the risk of secondary malignancy. It seems that radiobiologically based treatment planning taking into account the risk of secondary cancer can be established as an effective clinical tool for a more clinically relevant treatment optimization.

SU‐E‐T‐488: Secondary Malignancy Risks in Lung Cancer Radiotherapy with Helical Tomotherapy, Intensity Modulated Radiotherapy, and Conformal Radiotherapy

Purpose: The aim of the study is to examine the risk of inducing secondary malignancies in association with the clinical effectiveness of treatment plans in terms of tumor control and normal tissue complication probabilities. Methods: Four patients having been treated for lung cancer were examined. For each of them, three treatment plans were developed based on the Helical Tomotherapy (HT), MLC‐based Intensity Modulated Radiation Therapy (IMRT), and 3D‐Conformal Radiation Therapy (CRT) radiation modalities. The different plans were evaluated using the complication‐free tumor control probability (P+), the overall probability of injury (PI), the overall probability of control/benefit (PB), and the biologically effective uniform dose (BEUD). The risks for secondary malignancies in the spinal cord, heart and contra‐lateral lung were calculated for the three radiation modalities. Results: Regarding the overall evaluation of the different radiation modalities based on the P+ index, the average values of the HT, IMRT and CRT are 67.3%, 61.2% and 68.2%, respectively. The corresponding average values of PB are 75.6%, 70.5% and 71.0%, whereas the average values of PI are 8.3%, 9.3% and 2.8%, respectively. Regarding the risk for secondary cancer, for spinal cord the CRT modality produces the lowest average risk (1.4%) compared with the HT (2.1%) and IMRT (1.6%) radiation modalities. In heart, the lowest average risk is produced by IMRT (3.8%) compared with the HT (5.1%) and CRT (4.7%), whereas the three radiation modalities show almost equivalent results regarding the contra‐lateral lung (0.8% for HT, 0.9% for IMRT and 0.9% for CRT, respectively). Conclusion: The plans that appear to be more effective for the treatment are prone to show the highest risk of secondary malignancy. Radiobiologically‐based treatment planning taking into account the risk of secondary cancer can be established as an effective clinical tool for treatment optimization.

Focal brachytherapy for selected low-risk prostate cancers: A pilot study

To evaluate the feasibility and the early toxicity of focal brachytherapy in highly selected localized prostate cancer patients. Twenty-one patients underwent a focal brachytherapy between February 2010 and March 2012, representing 3.7% of the cases treated by our group during this period. Patient selection was based on (at least) two series of prostate biopsies and a high-resolution MRI. Only patients with very limited and localized tumors, according to strict criteria, were selected for the procedure. The technique used a real-time procedure with the implantation of free (125)I seeds and dynamic dose calculation. The prescribed dose for the focal volume was 145Gy. The treated volume corresponded to a mean value of 34% of the total prostatic volume (range, 20-48%). For the focal volume, the mean D90 and V100 was 183.2Gy (range, 176-188Gy) and 99.3% (range, 98.8-100%), respectively. The technique was performed in an hour and a half. When compared with a previous cohort treated by whole-prostate brachytherapy, urinary toxicity (International Prostate Symptom Score) was borderline reduced (p= 0.04) at 6 months only, whereas the recovery of the International Index of Erectile Function 5 was better (p= 0.014). The International Continence Score was nil in almost all cases as well as rectal toxicity. Focal treatment by brachytherapy is easily feasible with little acute toxicity. Further investigation is needed to assess the results in terms of tumor control and long-term toxicity.

Limb Salvage Surgery in Bone Tumors: A Retrospective Study of 50 Cases in a Single Center

Modular segmental replacement system (MSRS) is one of the options for Limb conservation surgery in bone tumors. The study analyses a single center experience of use of MSRS for limb conservation in cases of primary bone tumors. Retrospective analysis was done for a series of cases of limb salvage procedures done over a five year period. All Patients with bone tumors who underwent limb salvage procedures utilising MSRS prosthesis were included in the study. The patients' record were perused for pre operative staging; neoadjuvant therapy used, if any; surgical procedure done; follow-up for prosthesis related complications and overall survival achieved. Total of 50 cases studied,included 28 males and 22 females . Median age at diagnosis of 28 (10-73) years. Tumor localized in lower limb in 38 patients, and upper limb in 12 patients. Tumors were malignant in 28 patients (56%) and benign in 22 (44%). The most common diagnosis was osteosarcoma (21 patients (42%)) . The median resection length was 15cm (range 6-25). High grade tumors (grade 2a and 2b) was found in 27 of 29 cases(93.1%) . 14 patients had prosthesis related complications. The mean follow-up was 5years (range: 3-7). 42 patients of 50 were alive with the endoprosthesis at the last follow-up. Survival rate of prosthesis is 84%. The modular segmental-replacement system prosthesis favoured by us in limb sparing surgery for bone tumors results in satisfactory results in terms of tumor control and limb function.

Treatment strategies to reduce radiotherapy late effects in children

Late effects of treatment are an important cause of morbidity and mortality in childhood cancer survivors. The use of radiotherapy has been implicated as a risk factor for the development of many late complications. Several strategies have been employed in pediatric oncology to minimize the late effects of radiotherapy. These have included (1) omitting or delaying radiotherapy until the child is older, (2) decreasing radiotherapy doses and volumes by incorporating chemotherapy in the treatment regimen, (3) alteration of radiotherapy fractionation, (4) use of novel techniques to spare or minimize radiation dose to surrounding normal tissues, and (5) elimination of radiotherapy in favorable subsets of patients. In infants with brain tumors, delaying radiotherapy and giving chemotherapy until the child is 3 years old was a popular approach three to four decades ago with limited success with respect to tumor control. With the advent of modern radiotherapy technology, younger patients are now able to be treated with conformal techniques and reasonable neurotoxicity. Using chemotherapy to reduce doses of radiation therapy has been employed in standard-risk medulloblastoma, intracranial germinoma, Hodgkin lymphoma, and Wilms’ tumor. Likewise, the use of chemotherapy to reduce radiotherapy volumes has been employed in intracranial germinoma, Hodgkin lymphoma, and neuroblastoma and for the boost portion of treatments for rhabdomyosarcoma and Ewing sarcoma. There are a few phase III trials comparing conventional and hyperfractionated radiotherapy, but none of them have shown superiority of one over the other in terms of tumor control and late effects. Current protocols are testing the omission of radiotherapy in the most favorable subset of patients with Hodgkin lymphoma and Wilms’ tumor. Intensity-modulated radiation therapy is currently used in many children in developed nations. Proton therapy is available in a few centers; clinical results of treatment are accumulating regarding the effectiveness and long-term toxicity of this radiation modality.

Radiation therapy for vestibular schwannomas

Recently, new information on the natural course and on the results of radiation therapy of vestibular schwannomas has been published. The aim of this study is to summarize the most recent literature on the contemporary insights on the natural course and the results of the latest strategies of radiotherapy for vestibular schwannomas. After diagnosis only about one-third of all vestibular schwannomas will progress. Many patients do well with a 'wait and see' policy and, when necessary, radiation treatment has the advantage that tumor control rates are high (95%) and treatment-related side effects are very low. Different approaches to radiotherapy continue to evolve. Up till now stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) yield comparable results both in terms of tumor control and cranial nerve preservation. With new data available on hearing preservation after radiotherapy, a watchful waiting policy is a renewed matter of debate. When a vestibular schwannoma grows, radiotherapy (SRS or FSRT) may be a valuable treatment modality. Future clinical research (properly designed randomized trials) should focus on when and when not to treat, even if a vestibular schwannoma is not growing and on potential differences in long-term effects between SRS and fractionated radiotherapy.

Choroidal metastasis as the presenting feature in a case of testicular choriocarcinoma

A twenty-six year old male with decreased vision in right eye was diagnosed with non-rhegmatogenous retinal detachment. Further evaluation revealed a yet undiagnosed left testicular mass found to be choriocarcinoma on histopathology. Chemotherapy resulted in complete remission; however, there was no improvement in vision. There is a substantial risk of visual loss in the presence of ocular metastatic lesions. Early detection and treatment is highly effective in terms of tumor control and a more favorable survival and visual outcome. The onus of the ocular diagnosis lies on the ophthalmologist. The presence of a testicular origin tumor must be considered in a young male with intraocular metastasis.

Tomo Direct to Deliver Static Angle Tomotherapy Treatments

Radiation Therapy (RT) is a mainstay option for human cancer treatment, as it is employed as single agent or within combined modality approaches, with different timelines and aims (radical, neoadjuvant, adjuvant, palliation) and in almost all anatomic districts [1]. In recent years, significant developments have been introduced in RT planning a delivery, leading to improvements in terms of tumor control and normal tissue avoidance [2]. The Tomotherapy Hi-Art II system (Accuray Inc. , Sunnyvale, CA) is a RT platform able to deliver highly conformal intensity modulated radiotherapy (IMRT) plans within a helical geometry under image guidance (IGRT) [3]. A recent platform upgrade is named TomoDirect and it has been introduced in clinical practice in 2010, as a suitable solution for specific clinical context characterized by particular spatial relationships between target volumes (TVs) and organs at risk (OARs) allowing for beam arrangements constrained to a limited number of directions [4]. Tomotherapy delivers 6MV-IMRT through a rotating fan beam carved by a binary multileaf collimator (MLC), since the ring gantry rotates around the treatment couch as it progresses within the gantry bore across the delivery plane [4]. Beam modulation is obtained by a single row of binary leaves for each projected angle over a rotational interval of 7 degrees, up to a total of 51 projections for each gantry revolution. This approach provides robust conformality, abrupt dose fall off and reliable accuracy. However, since radiation is delivered all around the patient, a larger integral dose might become an issue, with low dose delivery (the so called ‘low dose bath’) to body segments that would only receive scatter radiation with a 3D conformal RT approach. During the optimization process, virtual structures named ‘blocks’ can improve dosimetry precluding radiation from specific volumes Thus, RT delivery is limited to fewer directions with a slender set of beamlets. Since the gantry rotational velocity remains constant, while the number of treatment directions decreases (with more gantry rotations needed to deliver the prescribed dose), this might result in unnecessary prolonged treatment time. Whenever the desired treatment is constrained to a limited number of incoming directions, this planning modality might represent an issue. TomoDirect (TD) combines static gantry positions, concomitant couch translation (along the craniocaudal direction) and MLC modulation. Specifically, while the patient is translated along the superior-inferior direction past the fixed fan beam path during delivery of each treatment field (defined as a fixed gantry angle and jaw width), the beam intensity is modulated by the binary collimator while the pitch (fraction of the jaw opening advanced by the treatment couch per evolution) regulates the degree of modulation in the cranio-caudal direction. Soon after the patient

Hypofractioned Radiation Therapy in the Treatment of Partial Breast: 30 Gy in Five Consecutive Fractions

Background and Purpose: Recent prospective studies have explored the partial breast irradiation (PBI) for patients with early-stage breast cancer using different technical approaches. The purpose of this study is to explore feasibility, tumor control and acute and late toxicity of a specific hypo-fractionated 3D-CRT when treating postmenopausal patients with early breast cancer with partial breast irradiation, using five fractions in five consecutive days. Materials and Methods: Ten patients, aged ≥ 70 underwent breast conservative surgery for invasive breast carcinoma with a complete microscopic resection; no lymphovascular invasion was found and negative axillary node status was assessed. Metal clips were positioned in the surgical bed at the time of surgery. All of the patients provided an informed consent for breast irradiation. Seven patients received Tamoxifen. Of the ten patients, five were treated for left breast disease, and five for right breast disease. The dose fractionation schedule was 3000 cGy delivered to the isocenter in 5 fractions (600 cGy/fr) using 6 MV photons. According to the linear quadratic model and an α/β ratio of 4 Gy this prescription is equivalent to 50 Gy in a standard 2-Gy fractionation schedule. Patients were treated in the supine position. A comercial breast board was used as immobilization device in order to keep the arms of the patient raised. The clinical target volume (CTV) was drawn with a uniform 1-cm three-dimensional margin around the surgical clips. The CTV was limited to 3 mm from the skin surface and 3 mm from the lung-chest wall interface. A three-dimensional margin was added to the CTV to obtain the planning target volume (PTV). The ipsilateral and controlateral breast, the ipsilateral and controlateral lung, heart and spinal cord were contoured as organs at risk (OAR). The treatment was developed using Precise Plan Treatment Planning System and four no-coplanar fields. The constraints used have been: uninvolved breast (ipsilateral breast-PTV): V15 ≤ 50%; heart: V3 ≤ 10%; ipsilateral lung: V10 ≤ 20%; controlateral lung: V5 ≤ 10% and controlateral breast: maximum dose ≤ 1 Gy. We required PTV coverage of ≥ 90%. Patient set-up was verified every day before treatment using portal images. No tumour bed boost was delivered. Clinical assessments of early normal tissue reaction were carried out every day during radiotherapy and 10 days after the end of the treatment. After radiotherapy, we visited all patients every 3 months during the first 2 years and every six month thereafter. Frontal and lateral pictures of the breast were taken on the first day of treatment (baseline), at the end of treatment, 10 days after the end of treatment and at the first follow-up. Any change in breast appearance compared with the baseline picture was scored on a four-point RTOG for acute and late radiation morbidity scoring scale. Results: No local or distant recurrences was observed and then confirmed by mammograms performed every year and breast ultrasound performed every six months. For acute and late toxicity, only 2 patients developed acute effects at the end of the treatment. Conclusion: The clinical outcomes observed in ten patients demonstrate a good feasibility of the schedule adopted both in terms of tumour control and acute and late toxicity, with good cosmetics results. Long term follow-up and a large number of patients will be needed for full evaluation.

Urethra sparing – potential of combined Nickel–Titanium stent and intensity modulated radiation therapy in prostate cancer

Background and purposeTo investigate a novel method for sparing urethra in external beam radiotherapy of prostate cancer and to evaluate the efficacy of such a treatment in terms of tumour control using a mathematical model. Materials and methodsThis theoretical study includes 20 patients previously treated for prostate cancer using external beam radiotherapy. All patients had a Nickel–Titanium (Ni–Ti) stent inserted into the prostate part of urethra. The stent has been used during the treatment course as an internal marker for patient positioning prior to treatment. In this study the stent is used for delineating urethra while intensity modulated radiotherapy was used for lowering dose to urethra. Evaluation of the dose plans were performed using a tumour control probability model based on the concept of uniform equivalent dose. ResultsThe feasibility of the urethra dose reduction method is validated and a reduction of about 17% is shown to be possible. Calculations suggest a nearly preserved tumour control probability. ConclusionsA new concept for urethra dose reduction is presented. The method relies on the use of a Ni–Ti stent as a fiducial marker combined with intensity modulated radiotherapy. Theoretical calculations suggest preserved tumour control.

New techniques in radiation therapy for head and neck cancer

The objective of this study was to assess the comparative effectiveness of intensity-modulated radiation therapy (IMRT), conformal and two-dimensional radiation therapy, proton beam, and carbon ion therapy in terms of tumor control and survival on the one hand and adverse events and quality of life on the other in irradiated head and neck cancer patients. A search of the literature was performed. At a given time, innovative techniques in radiation therapy may appear superior to routine irradiation techniques and clinical trials may therefore be considered unethical. IMRT, because of its superiority in terms of dose distributions and potential to preserve the salivary glands, has gradually replaced two-dimensional and conformal irradiation in routine use. The PARSPORT phase III trial is one among the rare trials to randomize two-dimensional and conformal irradiation against IMRT. It showed a 50% reduction in late xerostomia. Similarly, the relevance of clinical trials to prove the superiority of protons compared with photons is highly controversial. Although the expected benefit of particle beam therapy on dose distributions, local control, and quality of life seems sufficient for routine use without phase III trials, it should be noted that new toxicity profiles might be seen as was the case for IMRT (posterior alopecia, anterior mucositis, uncertainties of integral dose, and secondary cancers). Prospective clinical and medico-economic assessment, possibly in phase II trials, is therefore critically needed along with stringent quality assurance programs. Technological advances in radiation therapy clearly provide a benefit for patients despite the lack of level I evidence.