Searching standard parameters for volumetric modulated arc therapy (VMAT) of prostate cancer

Background Since December 2009 a new VMAT planning system tool is available in Oncentra® MasterPlan v3.3 (Nucletron B.V.). The purpose of this study was to work out standard parameters for the optimization of prostate cancer. Methods For ten patients with localized prostate cancer plans for simultaneous integrated boost were optimized, varying systematically the number of arcs, collimator angle, the maximum delivery time, and the gantry spacing. Homogeneity in clinical target volume, minimum dose in planning target volume, median dose in the organs at risk, maximum dose in the posterior part of the rectum, and number of monitor units were evaluated using student’s test for statistical analysis. Measurements were performed with a 2D-array, taking the delivery time, and compared to the calculation by the gamma method. Results Plans with collimator 45° were superior to plans with collimator 0°. Single arc resulted in higher minimum dose in the planning target volume, but also higher dose values to the organs at risk, requiring less monitor units per fraction dose than dual arc. Single arc needs a higher value (per arc) for the maximum delivery time parameter than dual arc, but as only one arc is needed, the measured delivery time was shorter and stayed below 2.5 min versus 3 to 5 min. Balancing plan quality, dosimetric results and calculation time, a gantry spacing of 4° led to optimal results. Conclusion A set of parameters has been found which can be used as standard for volumetric modulated arc therapy planning of prostate cancer

Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy – case report and review of literature

BACKGROUND: Modern radiotherapy (RT) reduces the side effects at organ at risk. However, skin toxicity is still a major problem in many entities, especially head and neck cancer. Some substances like chemotherapy provide a risk of increased side effects or can induce a "recall phenomenon" imitating acute RT-reactions months after RT. Moreover, some phototoxic drugs seem to enhance side effects of radiotherapy while others do not. We report a case of "radiation recall dermatitis" (RRD) one year after RT as a result of taking hypericin (St. John's wort). CASE REPORT: A 65 year old man with completely resected squamous cell carcinoma of the epiglottis received an adjuvant locoregional RT up to a dose of 64.8 Gy. The patient took hypericin during and months after RT without informing the physician. During radiotherapy the patient developed unusual intensive skin reactions. Five months after RT the skin was completely bland at the first follow up. However, half a year later the patient presented erythema, but only within the area of previously irradiated skin. After local application of a steroid cream the symptoms diminished but returned after the end of steroid therapy. The anamnesis disclosed that the patient took hypericin because of depressive mood. We recommended to discontinue hypericin and the symptoms disappeared afterward. CONCLUSION: Several drugs are able to enhance skin toxicity of RT. Furthermore, the effect of RRD is well known especially for chemotherapy agents such as taxans. However, the underlying mechanisms are not known in detail so far. Moreover, it is unknown whether photosensitising drugs can also be considered to increase radiation sensitivity and whether a recall phenomenon is possible. The first report of a hypericin induced RRD and review of the literature are presented. In clinical practise many interactions between drugs and radiotherapy were not noticed and if registered not published. We recommend to ask especially for complementary or alternative drugs because patients tend to conceal such medication as harmless

Dramatic radiotherapy response of a giant T4 cutaneous squamous cell carcinoma of the scalp with extensive bone destruction: a case report

Background Patients with large cutaneous squamous cell carcinoma of the scalp are a treatment challenge. We report a case of dramatic radiotherapy response of a patient with a giant cutaneous squamous cell carcinoma of the scalp with extensive skull destruction and suspected infiltration of the dura mater and superior sagittal sinus. This case is the first report of this kind in the literature that shows that large bone defects can heal with the resolution of tumor and inflammation by secondary intention without surgical reconstruction. We want to put an end to concerns about radiocurability of tumors with extensive bone involvement, and show sustained complete response after definitive radiotherapy and programmed cell death protein-1 inhibiting antibody therapy. Case presentation A 74-year-old White man presented with a 7.2 × 6.8 × 5.5 cm painless tumor on the right parietal region of the scalp. Medical imaging revealed widespread destruction of the skull and suspected infiltration of the dura mater and superior sagittal sinus. Biopsies showed cutaneous squamous cell carcinoma (cT4a cN0 cM0, stage IVA). The patient was treated with a total dose of 60 Gy, at 2 Gy per daily fraction with volumetric modulated arc therapy using 6 megavoltage photons. The biologically effective dose (alpha/beta 10 Gy) was 72 Gy. The tumor response correlated with dose received. The patient had a massive tumor necrosis secondary to tumor shrinkage after 18 fractions (36 Gy, biologically effective dose 43.2 Gy). Leakage of cerebrospinal fluid did not occur. Radiotherapy did not hamper the patient’s quality of life. The patient had a clear regression of the initial tumor on the final day of radiotherapy. The bone defect healed by secondary intention without surgical interventions. The patient achieved a complete response with a good cosmetic result after 82 days follow-up. He started a programmed cell death protein-1 inhibiting antibody therapy with cemiplimab 2 months after radiotherapy, and is now at 10 months follow-up without evidence of recurrence. Conclusion Definitive radiotherapy is a safe and highly effective therapy for giant tumors of the scalp with extensive bone destruction. We report a sustained complete response with a good cosmetic result after secondary wound healing

The influence of radiotherapy techniques on the plan quality and on the risk of secondary tumors in patients with pituitary adenoma

Background This planning study compares different radiotherapy techniques for patients with pituitary adenoma, including flatness filter free mode (FFF), concerning plan quality and secondary malignancies for potentially young patients. The flatness filter has been described as main source of photon scatter. Material and methods Eleven patients with pituitary adenoma were included. An Elekta Synergy (TM) linac was used in the treatment planning system Oncentra (R) and for the measurements. 3D plans, IMRT, and VMAT plans and non-coplanar varieties were considered. The plan quality was evaluated regarding homogeneity, conformity, delivery time and dose to the organs at risk. The secondary malignancy risk was calculated from dose volume data and from measured dose to the periphery using different models for carcinoma and sarcoma risk. Results The homogeneity and conformity were nearly unchanged with and without flattening filter, neither was the delivery time found substantively different. VMAT plans were more homogenous, conformal and faster in delivery than IMRT plans. The secondary cancer risk was reduced with FFF both in the treated region and in the periphery. VMAT plans resulted in a higher secondary brain cancer risk than IMRT plans, but the risk for secondary peripheral cancer was reduced. Secondary sarcoma risk plays a minor role. No advantage was found for non-coplanar techniques. The FFF delivery times were not shortened due to additional monitor units needed and technical limitations. The risk for secondary brain cancer seems to depend on the irradiated volume. Secondary sarcoma risk is much smaller than carcinoma risk in accordance to the results of the atomic bomb survivors. The reduction of the peripheral dose and resulting secondary malignancy risk for FFF is statistically significant. However, it is negligible in comparison to the risk in the treated region. Conclusion Treatments with FFF can reduce secondary malignancy risk while retaining similar quality as with flattening filter and should be preferred. VMAT plans show the best plan quality combined with lowest peripheral secondary malignancy risk, but highest level of second brain cancer risk. Taking this into account VMAT FFF seems the most advantageous technique for the treatment of pituitary adenomas with the given equipment

Stereotactic radiosurgery of brain metastases: a retrospective study

Background Single-fraction stereotactic radiosurgery (SRS) is an established standard for radiation therapy of brain metastases although recent developments indicate that multi-fractionated stereotactic radiotherapy (FSRT) results in lower radiation necrosis especially for larger metastases, and the same or even better local control in comparison to SRS. Methods Seventy-two patients with 111 brain metastases received SRS with a single dose of 18 Gy between September 2014 and December 2021. The dose prescription was either 18 Gy given to the enclosing 80% isodose with a normalization to Dmax = 100% of 22.5 Gy (part I) or 18 Gy = D98, while D0.03 cc of 21.6–22.5 Gy was accepted (part II). The study retrospectively evaluated local progression-free survival (LPFS), response on the first follow-up magnetic resonance imaging (MRI), and radiation necrosis. Results Melanoma brain metastases (n = 44) were the most frequent metastases. The median gross tumor volume (GTV) was 0.30 cm³ (IQR, 0.17–0.61). The median follow-up time of all patients was 50.8 months (IQR, 30.4–64.6). Median LPFS was 23.5 months (95%CI 17.2, 29.8). The overall LPFS rates at 12-, 18-, 24- and 30 months were 65.3%, 56.3%, 46.5%, and 38.8%. Brain metastases with radioresistant histology (melanoma, renal cell cancer, and sarcoma) showed a 12-month LPFS of 60.2%, whereas brain metastases with other histology had a 12-month LPFS of 70.1%. The response of brain metastases on first follow-up MRIs performed after a median time of 47 days (IQR, 40–63) was crucial for long-term local control and survival. Eight brain metastases (7.2%) developed radiation necrosis after a median time of 18.4 months (IQR, 9.4–26.5). In multivariate analyses, a GTV > 0.3 cm³ negatively affected LPFS (HR 2.229, 95%CI 1.172, 4.239). Melanoma, renal cell cancers, and sarcoma had a lower chance of LPFS in comparison to other cancer types (HR 2.330, 95%CI 1.155, 4.699). Conclusions Our results indicate a reasonable 1-year local control of brain metastases with radiosensitive histology. Radioresistant metastases show a comparatively poor local control. Treatment refinements merit exploration to improve local control of brain metastases. Trial registration This study is retrospectively registered (ethics approval number 23-3451-104)

Volumetric-modulated arc therapy and intensity-modulated radiation therapy treatment planning for prostate cancer with flattened beam and flattening filter free linear accelerators

This study on patients with localized prostate cancer was set up to investigate valuable differences using flattened beam (FB) and flattening filter free (FFF) mode in the application of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT). For ten patients, four different plans were calculated with Oncentra planning system of Elekta, using Synergy machines: IMRT and VMAT, with and without flattening filter. Homogeneity and conformity indexes, dose to the organs at risk, and measurements of peripheral dose and dosimetric plan verification including record of the delivery times were analyzed and statistically evaluated. The indexes for homogeneity and conformity (CTV and PTV) are either advantageous or not significantly different for FFF compared to FB with one minor exception. Regarding the doses to the organs at risk and the measured peripheral dose, equivalent or lower doses were delivered for FFF than with FB. Furthermore, the delivery times were significantly shorter for FFF. VMAT compared to IMRT reveals benefits or at least equivalent values. VMAT-FFF combines the most advantageous plan quality parameters with the shortest delivery times and reduced peripheral dose and is therefore recommended for the given equipment and cancer localization

Volumetric Modulated Arc Therapy (VMAT) Treatment Planning for Prostate - A Comparison of Flatness Filter Free (FFF) and Flat Beam Plans

Introduction Linear accelerators (Linacs) with Flatness Filter Free (FFF) mode obtain a much higher dose rate by omitting the flatness filter. The resulting inhomogeneous dose distribution is compensated by fluence modulating techniques like IMRT or VMAT. This planning study compares VMAT plans for patients with prostate carcinoma. Optimizations were performed using both modes: flattened beam (FB) and FFF. The aim of this study is to evaluate the plan quality and the number of monitor units (MU). Material and Methods Data sets of 10 patients with localized prostate cancer and reliable dose volume objectives were used for this retrospective planning study. A simultaneous integrated boost radiation therapy aims at a minimum dose of 71.0Gy and maximum of 74.2Gy in the CTV and a minimum dose of 59.4Gy in the PTV in 33 fractions. The posterior rectum wall is limited to 50.0Gy. The median values of rectum and urinary bladder are set to 50.0Gy. Additionally the maximum dose to the rectum is set to 74.2Gy. The VMAT parameters in the treatment planning system (TPS) Oncentra® External Beam v4.5 are set to: Single Arc rotation (182°-178°), collimator 45°, maximum delivery time 110s, gantry spacing 4°, and collapsed cone algorithm. The linac Synergy Agility offers a dose rate of 550MU/min (FB) and 1700MU/min (FFF). The leaves have a width of 5mm projected to the isocenter. The following parameters are evaluated: average dose DAv and homogeneity H = (D5–D95)/DAv in the CTV, minimum dose in the PTV represented by the D98PTV-CTV of the difference volume of PTV and CTV, maximum dose in the posterior rectum wall represented by the D2Rpost, median dose to rectum D50R and urinary bladder D50B, and the number of MU. Results Generally the dose volume statistics are very close for both modes. Taking the average dose in the CTV as normalization value, the maximum does not exceed 107%. The minimum dose in the PTV has been reached in one plan of each group only. The objectives for the median values in rectum and urinary bladder as well as maximum dose to the posterior rectum wall have been achieved in all cases. The only statistically significant difference for both groups is the number of MU which is about 10% lower for the FB plans. Discussion The plans for both modes show a good homogeneity in the CTV. The minimum dose to the PTV and the maximum dose to the posterior rectum wall are counterworking objectives which resulted in favour for the rectum for the given weights of the objectives. The high dose rate of the FFF mode aims at shorter treatment times which would reduce intrafractional organ motion. Measurements of the delivery times will be performed and discussed in the presentation

EP-1615: Second cancer risk after radiation of localized prostate cancer with and without flattening filter

Purpose: Radiotherapy is a standard treatment modality with curative intent for localized prostate cancer. Prostate cancer is a disease of elderly men. Nevertheless these patients have a remaining life span of ten years or more. Radiotherapy compared to surgery may increase the risk for second cancer. Minimizing this risk can be one criterion in deciding for a specific technique. Therefore we compared the organ equivalent dose (OED) and excess absolute risk (EAR) for second cancer for different treatment techniques. Material and methods: For ten patients four different plans were calculated, using a seven field intensity modulated radiotherapy (IMRT) and a single arc volumetric modulated arc therapy (VMAT) with and without flattening filter. The optimization was performed as simultaneous integrated boost in 33 fractions, aiming for 59.4 Gy minimum dose to the PTV and 71.0 Gy minimum dose and 74.2 Gy maximum dose to the CTV. The OED was computed for the urinary bladder and the rectum from dose volume histograms for the linear-exponential and the plateau dose-response model. The EAR can be derived from the OED, taking age modifying parameters into account. The statistical analysis was performed using the Wilcoxon test in IBM® SPSS® Statistics 23 (IBM Corporation). Results: Within one technique (IMRT or VMAT) the average value of the OED is lower for the flattening filter free (FFF) mode compared to flat beams (FB) in both organs and for both dose-response models with one exception: In the urinary bladder it is the other way round for IMRT and the linear-exponential model. These results are statistically significant (level of significance 5%). The results for VMAT are statistically significant for the rectum only in both models. Comparing IMRT and VMAT the results are ambiguous: For the linear-exponential model the OED is lower with IMRT for both FB and FFF, for the plateau model lower OEDs are achieved with VMAT. All results are significant, except of one (lin-exp. model, FFF, urinary bladder, p = 7.4%). Conclusion: Some statistically significant differences have been found for the different treatment techniques and modes. However, they depend on the dose-response model. For the plateau model the lowest EAR is found for VMAT FFF in both organs at risk, for the linear-exponential model IMRT FB shows the minimum values. Plan quality and efficiency should additionally be regarded before the decision for a specific technique and mode

Fractionated stereotactic radiotherapy of brain metastases: results of a retrospective study

Background Lasting local control of brain metastases following stereotactic radiotherapy is becoming increasingly relevant since systemic treatment constantly improves the prognosis of patients with extracranial metastases. Methods 73 patients with 103 brain metastases received hypofractionated stereotactic radiotherapy (FSRT) in 6 fractions of 5 Gy between January 2017 and December 2021 at the University Hospital Regensburg, Germany. The study retrospectively evaluated local progression free survival (LPFS), overall survival (OS) and distant brain progression free survival (DPFS) of patients without prior radiotherapy of the brain. Response rate and brain radiation necrosis were reported. Cox proportional hazard models evaluated prognostic factors of OS and LPFS. Results The median patient age was 61.0 years (Interquartile range, IQR 51.0, 67.5). The most common tumor types were malignant melanoma (34.2%) and non-small cell lung adenocarcinoma (26.0%). The median gross tumor volume (GTV) was 0.9 cm³ (IQR 0.4, 3.6). The median follow-up time of all patients was 36.3 months (95%CI 29.1, 43.4). The median OS was 17.4 months (95%CI 9.9, 24.9). Overall survival rates at 6-, 12-, 18-, 24-, and 30 months were 81.9%, 59.1%, 49.0%, 41.3%, and 37.2%, retrospectively. The mean LPFS was 38.1 months (95%CI 31.4, 44.9), while the median LPFS has not been reached. LPFS rates at 6-, 12-, 18-, 24- and 30 months were 78.9%, 68.7%, 64.3%, 61.6% and 58.7%, retrospectively. Median DPFS of all patients was 7.7 months (95%CI 6.1, 9.3). Six, 12-, 18-, 24- and 30 months DPFS rates were 62.1%, 36.3%, 31.1%, 24.8% and 21.7%. Five brain metastases (4.8%) developed brain radiation necrosis. In multivariate analysis, the number of brain metastases negatively affected LPFS. Non-melanoma and non-renal cell cancer was associated with a higher chance of LPFS in comparison to other cancer. A GTV > 1.5 cm³ translated into a higher risk of death compared to a GTV ≤ 1.5 cm³ and Karnofsky performance score was predictive of OS. Conclusions FSRT in 6 fractions of 5 Gy seems to be an effective treatment with an acceptable local control for patients with brain metastases although melanoma and renal cell cancer seem to have a worse local control in comparison to other cancer

Simultaneous integrated boost therapy of carcinoma of the hypopharynx/larynx with and without flattening filter - a treatment planning and dosimetry study

Background: The aim of this study was to investigate if the flattening filter free (FFF) irradiation mode of a linear accelerator (linac) is advantageous as compared to the flat beam (FF) irradiation mode in intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) for carcinoma of the hypopharynx/larynx. Methods: Four treatment plans were created for each of 10 patients for an Elekta Synergy linac with Agility collimating device, a dual arc VMAT and a nine field step and shoot IMRT each with and without flattening filter. Plan quality was compared considering target coverage and dose to the organs at risk. All plans were verified by a 2D-ionization-chamber-array and delivery times were compared. Peripheral point doses were determined as a measure of second cancer risk. The Wilcoxon test was used for statistical analysis with a significance level of 0.05. Results: Plan quality was similar for all four treatment plans without statistically significant differences of clinical relevance. The clinical goals were met in all plans for the PTV-SIB (V-95% > 95%), the spinal cord (D1ccm < 45 Gy) and the brain stem (D-1ccm < 48 Gy). For the parotids, the goal of D-50% < 30 Gy was met in 70% and 60% of the plans for the left and right parotid respectively, and the V-95% of the SIB reached an average of 94%. Delivery times were similar for FF and FFF and significantly decreased by around 70% for VMAT as compared to IMRT. Peripheral doses were significantly reduced by 18% in FFF mode as compared to FF and by 26% for VMAT as compared to IMRT. Lowest peripheral doses were found for VMAT FFF, followed by VMAT FF. Conclusions: The FFF mode of a linear accelerator is advantageous for the treatment of hypopharynx/ larynx carcinoma only with respect to reduction of second cancer induction in peripheral organs for the combination of Elekta Synergy linacs and Oncentra (R) External Beam v4.5 treatment planning system. This might be of interest in a therapy with curative intent