Ultrahypofractionated CyberKnifeTM based stereotactic radiotherapy versus conventional radiotherapy in patients with prostate cancer - acute toxicity evaluation in two phase II prospective studies.

Our purpose was to compare the acute toxicity of ultrahypofractionated CyberKnifeTM based stereotactic radiotherapy (SBRT Arm) and conventional radiotherapy (EBRT Arm) in prostate cancer patients. Two-hundred-sixteen men with prostate cancer were enrolled in our prospective studies. One-hundred and nine were irradiated using CyberKnife to total dose of 36,25 Gy in 5 fractions. One-hundred and seven were irradiated conventionally to total dose of 76 Gy in 38 fractions. Mean age of patients was 69. Acute genitourinary (GU) and gastrointestinal (GI) adverse-events were collected. The maximal acute toxicity EORTC/RTOG score was assumed. A total of 41%, 44%, 12% and 3% of patients presented grade 0, 1, 2 and 3 acute genitourinary toxicity in SBRT arm, respectively. A total of 21%, 33%, 43% and 3% of patients demonstrated acute grade 0, 1, 2 and 3 genitourinary toxicity in EBRT arm. A significant difference between number of patients with grade 2 GU toxicity was observed (p-0.000) and between patients without any toxicity (p-0.0017).A significant difference in frequency of acute GI toxicity between both groups was observed, too. 71% vs. 44% had no toxicity (p-0.0001), and 3% vs. 18% (p-0.0004) presented grade 2 GI toxicity in SBRT and EBRT arms respectively.The acute toxicity rates of fractionated stereotactic radiotherapy is lower compared to conventional irradiation.

CyberKnife stereotactic radiosurgery and stereotactic ablative radiation therapy of patients with prostate cancer bone metastases.

The aim of the study was to evaluate the effectiveness and toxicity of CyberKnife (CK) stereotactic radiosurgery (SRS) and stereotactic ablative radiation therapy (SABR) of patients with prostate cancer bone metastases. Analysis of prognostic and predictive factors was also performed. Material consisted of 51 patients with 71 bone oligometastases treated using CK SRS/SABR. In half of the patients single lesion was treated, in half 2-5 lesions. Median PSA concentration at the time of metastasis detection was 5.75 ng/ml. Total dose of 6-45Gy (median 20) was delivered with 1-5 fractions of 6-15 Gy (median 9). Biologic equivalent dose (BED) (α/ß=1.6) over 100 Gy was delivered to 45 lesions (63%) in 38 patients (75%). In statistical analysis Kaplan-Meier method, log-rank test and the Cox proportional hazard model were used. One-, two- and three-year overall survival (OS) was 90%, 76% and 70%, respectively. All patients having PSA concentration lower that 1 ng/ml at last control lived at least three years. One-, two- and three- year local control (LC) was 97%, 70% and 30%. Patients with PSA below 20 ng/ml at the time of metastasis detection had better local control of lesions and lower PSA at the last control. Median of PSA concentration after CK based SRS/SABR remains stable during first 12 months of follow-up, dropped during the next months and at last control was comparable to initial level. Median PSA at last control in patients without disease progression was 1.67ng/ml and 20 patients had PSA below 1.0ng/ml. At the last control 59% of patients had no other metastases. Rapid pain decrease was observed in analysed group and during each control about 90% of patients had pain relief. No major toxicity was observed, 3 patients suffered from fracture of irradiated bone.SRS/SABR of prostate cancer bone oligometastases provides good LC of lesions, excellent pain control without additional toxicity. Patients with PSA concentration below 20ng/ml at the time of metastasis detection have better LC and PSA concentration response.

Acute toxicity of robotic ultrahypofractionated radiotherapy CyberKnifeTM in prostate cancer patients.

Our purpose was to evaluate the toxicity of CyberKnifeTM based fractionated stereotactic radiotherapy (FSRT) in prostate cancer patients. One-hunred-thirty-two men with low (62) and intermediate (70) prostate cancer were enrolled in our prospective study. Mean age was 69. Total dose of 36,25 Gy in 5 fractions was prescribed. Image guided FSRT was performed on CyberKnife. Minimum follow-up ranged from 3 to 28 months. EORTC/RTOG scale was used to evaluate toxicity. A total of 47%, 10% and 2% of patients presented grade 1, 2 and 3 acute genitourinary toxicity, respectively. In 25% and 3% of patients, respectively, grade 1 and 2 acute gastrointestinal toxicity was observed. No significant association between acute grade ≥ 2 toxicity and clinical factors: age, androgen deprivation therapy or infections were found. Neither CTV nor PTV volumes had significant impact on acute grade ≥ 2 toxicity. Late toxicity was assessed in 104 patients. In 16% and 1% of patients late GU toxicity in grade 1 and 2, respectively, was presented. Late GI toxicity grade 1, 2 and 3 occurred in 8%, 3% and 1% of patients, respectively. The acute toxicity rates of fractionated stereotactic radiotherapy are low. Early data suggest also low late toxicity rates.

Daily image-guidance in prostate cancer radiotherapy - implications for treatment margins.

UNLABELLED: Our purpose was to evaluate interfractional organ and patient movement during radiotherapy of prostate cancer and to calculate the necessary CTV to PTV margins. Fifty patients irradiated between 2009 and 2011were included into the prospective study. The 2D-2D KV system combined with the intraprostatic fiducial marker were used for daily position verification. Based on the 8629 measurements of isocentre displacement an interfractional motion of pelvis and prostate was evaluated. The CTV to PTV margins were calculated. Margins of 0.7 cm (AP), 1 cm (SI) and 0.35 cm (LR) are necessary when only bony based IGRT is performed. Margins of 1.0 cm, 1.8 cm and 0.5 cm in AP, SI and LR directions respectively are necessary in case of no IGRT.There was no clinically relevant changes in patient/target mobility throughout the whole treatment. The IGRT is essential for state of art radiotherapy of prostate cancer. Necessary CTV to PTV margins are much bigger in case of no IGRT performed. Changing of margins size throughout regular treatment is not necessary. KEYWORDS: IGRT, prostate cancer, fiducial marker.

Split-course accelerated hyperfractionated irradiation (CHA-CHA) as a sole treatment for advanced head and neck cancer patients-final results of a randomized clinical trial.

OBJECTIVE: Evaluation of the efficacy and toxicity of split-course accelerated hyperfractionated irradiation (CHA-CHA) as a sole treatment for advanced head and neck (H&N) cancer patients. METHODS: We enrolled 101 patients (39 in CHA-CHA and 37 in conventional (Conv.) arm completed the treatment). The CHA-CHA arm patients were irradiated twice a day, 7 days a week, using a fraction dose (fd) of 1.6 Gy up to 64 Gy with an 8-day gap in midterm. Patients in the control (Conv.) arm group were irradiated with a fd of 2 Gy, five times a week to a total dose of 72-74 Gy in the overall treatment time of 50-53 days. Quality of life (QOL) and acute mucosal reaction were evaluated during radiotherapy (RT). After RT, we followed the effect of treatment, QOL, performance status and adverse effects of radiation. For statistical analysis mainly a hierarchical multilevel modelling was used. RESULTS: QOL was most deteriorated in the CHA-CHA arm; the CHA-CHA scheme also caused a relatively stronger acute injury. There were no significant differences in late adverse effects. In the CHA-CHA arm in 35% and in Conv. arm in 30% of patients, disease was controlled during follow-up. Tumour regression 1 year after the treatment was significantly better in the CHA-CHA arm. However, the overall survival rate analysis did not show significant difference between both arms. CONCLUSION: Despite differences in treatment results, we cannot conclude that split-course accelerated hyperfractionated irradiation is superior to conventionally fractionated RT as a sole treatment for advanced H&N cancer patients. ADVANCES IN KNOWLEDGE: Obtained results in the context of published data support the statement that altered fractionations alone do not give an advantage for advanced H&N cancer patients.

Linac based radical radioablation of liver tumors.

Due to the low percentage of resectable liver tumors, new alternative treatment modalities are used. Among them, radioablation, that is, by using a limited number of high dose radiation. The aim of this study was to evaluate the effectiveness of liver tumor radioablation at 36 Gy delivered in three fractions. The analyzed material comprised of 65 liver tumors. In 61 cases, we irradiated metastases (20 rectal cancers) and in 4 primary liver tumors. Radioablation, was done using 6 and 20 MV photons with a fraction dose of 12 Gy once a week up to a total dose of 36 Gy. During the follow-up we measured tumor diameters, and for our statistics we used a classical linear regression and the Bayesian approach. Mild and moderate late toxicity was observed. We found a significant absolute and relative decrease in tumor size during the first 6 months from the whole analyzed group. In subgroups with adenocarcinomas, metastases of gastrointestinal tract (GI) cancers, metastases of cancers other than GI cancers, and in the subgroup in which 2D-2D kV system (IGRT) and respiratory gating was used. The percentage of tumors with local control (lack of "in field" progression) after 6 months was 89%. The obtained results permit us to conclude that gated SBRT of liver tumors is an effective and safe treatment modality resulting in a significant regression of liver tumors and that the highest degree of tumor size reduction can be expected for metastases of non-gastro intestinal tract cancers.

Linac-based stereotactic radiosurgery for brain arteriovenous malformations.

AIMS: Most papers dealing with radiosurgery for cerebral arteriovenous malformations (AVMs) present the results of gamma-knife treatment, whereas linac radiosurgery is becoming increasingly popular. Moreover, there is still much uncertainty about the rationale of combined endovascular and radiosurgical treatment. The aims of this study were to evaluate obliteration and rebleeding rates, and to determine factors influencing obliteration and adverse effects after linac-based stereotactic radiosurgery for cerebral AVMs. MATERIALS AND METHODS: Records of 62 consecutive patients were analysed. Thirty-one had partial embolisation, five surgery, 29 had no prior treatment. The mean follow-up was 28.4 months. The mean volume treated was 11.7cm(3) and included embolised portions of AVMs. Actuarial obliteration rates and annual bleeding hazard rates after radiosurgery were calculated using Kaplan-Meier survival and life table analyses. RESULTS: Actuarial obliteration rates after 1, 2 and 3 years of follow-up were 17, 36 and 40%, respectively. Prior embolisation did not influence the obliteration rate. In 77.3% of patients, obliteration occurred during the first 2 years of follow-up. Annual bleeding hazard rates after stereotactic radiosurgery were 3.4 and 1.1% during the first and second year of follow-up, respectively. Non-symptomatic imaging abnormalities were detected in 33.9% of patients after a median time of 8.8 months. The Spetzler-Martin grade, AVM score, radiation dose, volume and AVM nidus < 3cm significantly influenced the probability of obliteration. A dose less than 15Gy significantly reduced the probability of obliteration. CONCLUSION: At least a 3 year follow-up is required to accurately assess the outcome. The best effects of the treatment are achieved for small (<3cm), low-grade lesions with a low AVM score. The bleeding risk after stereotactic radiosurgery gradually decreases.

Retrospective evaluation of radiotherapy in plantar fasciitis.

Plantar fasciitis is a common painful syndrome that is usually treated by irradiation with a fraction dose (fd) of 1 Gy up to a total dose (TD) of 6 Gy according to clinical experience. By analysing our experiences with numerous former patients, we have attempted to find the relationship between dose and effect. To evaluate the effectiveness of radiotherapy and assess the impact of fd and TD in plantar fasciitis radiotherapy, we assessed 1624 irradiations (856 patients) performed using a fd of 1-3 Gy and a TD of 1-45 Gy. Analysis was carried out on the 623 irradiations (327 patients) for which complete follow-up data were available. The mean follow-up period was 74 months. The following parameters were evaluated: pain relief level; period of anaesthetic effect preservation after treatment; presence of pain and the timing of its appearance; and the intake of analgesic drugs at the last follow-up. After treatment, 48% of the patients reported a lack of pain, 21% reported pain relief greater than 50% and 17% reported pain relief less than 50%. The mean pain relief duration was 72 months. The last follow-up found that pain at rest afflicted 25% of the patients, and pain during walking afflicted 32%. A dose-effect relationship was not found. In conclusion, radiotherapy is an effective treatment for plantar fasciitis. A fd of 1.5 Gy and TD of 9 Gy should probably not be exceeded.

Split-course accelerated hyperfractionation (CHA-CHA) for advanced head and neck cancers -- preliminary results.

The purpose of the study was to evaluate toxicity and effectiveness of the split course, accelerated hyperfractionation with a planned gap (CHA-CHA) on a base of the pilot group treatment results. The material consisted of 27 patients with advanced (T2N2c-3, T3-4N2), oral cavity, oro- hypopharynx and larynx cancers, irradiated with a df 1.6 Gy twice a day, with 6-hour gap, up to TD 64 Gy in 28 days, with 8-day gap in a middle. Mean tumor dimensions were 4.2 and 3.9 cm in X and Y axes, respectively and mean nodes dimensions 3.9 cm in both axes. The course and intensity of the mucositis were evaluated in the Dische scale together with the degree of a tumor and nodes regression. Survival analysis and dependencies evaluation between physical/biological factors and treatment results were performed. The mucositis intensity was high from 2nd to 5th week (the highest mean - 15 Dische points in 4th week), but on acceptable level. 54.5% of CR of the tumor and 57.1% of nodes were noted. Survival analysis showed 44% of a 2-year and 35% of a 4-year OS and 44% of a 2-year and 38% of a 4-year survival excluding deaths from distant metastases. Correlation between the hemoglobin level and the nodal regression two months after the radiotherapy (p=0.01), showed the tumor diameter and TCP (p=0.047), the OS and the nodes diameter (p=0.004), the PS (p=0.02) and the hemoglobin level (p=0.04). CHA-CHA could be a valid method in advanced head and neck cancer treatment but its efficacy should be confirmed in randomized phase of trial.

Evaluation of efectiveness of palliative radiotherapy alone or combined with surgery in patients with bone metastases.

Material and methods. The retrospective analysis results of palliative radiotherapy alone or combined with surgery of 200 patients with bone metastases are presented. All patient were irradiatated, 47 of them were operated before or after radiotherapy. General performance status, pain relief, movement efficiency, analgetic drugs and bisphosphonates administration, disease progress and bone reossification were assesed 1, 2, 3, 6, 12 months after the treatment and durning the last examination.
Results. The complete or partial pain relief were observed in 47% of patients 1 month, 56% two months 41% in 3, 38% 6 months after the treatment. 26% reported pain relief 1 year after irradiation and 33% at the last visit
The Kaplan Maier survival analysis shows ststistically significant longer survival for patient treated by combined treatment, women, patients with multiple bone metastases and patients with metastases located in long bones and patients without symptoms of spine compression. Spearman analysis reveals correlation beetween performance status and follow up. There are no correlations between radiation dose, bisphosphonates administration and pain relief, pathology of tumor and follow up.
Conclusions. The obtained results suggests that radiotherapy is effective method of analgetic treatment in bone metastases and that radiotherapy associated with surgery improves survival.

[The evaluation of the effectiveness of half-body irradiation as palliative treatment in patients with multiple bone metastases]. / Ocena skutecznosci napromieniania polowy ciala jako paliatywnej i przeciwbólowej radioterapii u chorych z mnogim rozsiewem nowotworowym w kosccu.

The results of simplified method of hemibody irradiation of 23 patients with multiple painful bone metastases are presented. In all cases without proven bone metastases in skull and distal part of limbs, these parts of the body were excluded from irradiated field. The study comprised 25 cases of hemibody irradiation. The degree of pain relief and performance status improvement was assessed one and two months after treatment, depending on clinical and histopathological diagnosis and type of bone metastases. The best symptomatic results were obtained in the cases of multiple myelomas (100% of pain relief), prostate cancers (the average degree of 78%) and lung cancers (88%). Considering histopathological diagnosis, the best answer was found in multiple myeloma and squamous cell cancer (88%). Taking into account type of metastases the best result was obtained in the cases of osteolytic metastases (65%). No difference between upper and lower hemibody irradiation was found. The statistically significant correlation between pain relief, performance status improvement and decrease of analgetics use was found. The obtained results suggest that presented simplified form of hemibody irradiation is an effective symptomatic treatment modality in the cases with multiple painful bone metastases, giving an increase of life quality without significant radiation morbidity.

[Use of radiotherapy in treatment of painful scapula-humeral periarthritis]. / Zastosowanie radioterapii w leczeniu zespolów bólowych barków.

In 10 cases of painful scapulo-humeral periarthritis radiotherapy was used. In all cases conventional anti-inflammatory treatment was unsuccessful or impossible to deliver. Patients were treated using gamma 60Co radiation and 6 Gy was delivered in 1 Gy fractions over 8 days. The average degree of pain relief and improvement of limb mobility was assessed after radiotherapy completion, 1 week, 7 weeks after treatment and at final-up. The degree of pain relief was respectively 27%, 72%, 85% and 93%. Significant improvement of limb mobility was noted in all cases. Obtained results allow to conclude that anti-inflammatory radiotherapy is an effective treatment of painful scapulo-humeral periarthritis.

The efficacy of radiotherapy for vertebral hemangiomas.

Vertebral hemangiomas are benign, slowly growing tumors sometimes causing local pain in the spine and/or neurologic disorders. The present paper includes 14 cases of painful vertebral hemangiomas treated by radiotherapy. All patients were irradiated using standard fractionation scheme with a total dose 20-30 Gy. One month after the treatment complete pain relief was noted in 36% of cases, five months later in 67% of cases, but in the remaining cases partial pain relief was noted. No correlation between treatment outcome and different biological and technical factors was found. No dose-response relationship was noted. The results suggest that anti-inflamatory effect of radiation plays the major role in this kind of treatment and that radiotherapy for vertebral hemangiomas is easy, short and highly effective analgetic treatment modality.

Efficacy of radiotherapy for giant cell tumor of bone: given either postoperatively or as sole treatment.

PURPOSE: The aim of this paper is to evaluate efficacy of radiotherapy for giant cell tumor of bone given either postoperatively or as sole treatment, and to assess prognostic factors for treatment outcome. METHODS AND MATERIALS: The study includes 37 patients. In 9 cases, soft tissue involvement was noted. Nonradical operation followed by radiotherapy was given to 23 patients, and 14 patients received irradiation only. Total dose of 39--64 Gy was delivered. The average follow-up was 5 years. Probability of local tumor control (LTC) depending on the treatment strategy was calculated, and prognostic factors were assessed. RESULTS: LTC was noted in 31 cases. Ten-year LTC for surgery with irradiation was 83% and 69% for radiotherapy alone; however, this difference was not statistically significant. For tumors smaller than 4 cm LTC probability was above 90%, and it decreased to less than 60% for tumors larger than 8.5 cm. No dose-response relationship has been found. In 7 cases, late normal tissue effect occurred. CONCLUSIONS: Giant cell tumors of bone can be considered as radiosensitive and radiotherapy with total dose of 40--45 Gy seems to be an effective sole treatment especially for tumors smaller than 4 cm in diameter. For larger tumors, surgery combined with postoperative radiotherapy should be considered.

The impact of delivered dose errors on local control of irradiated advanced laryngeal cancer.

On the basis of 1,015 entrance and 863 exit dose in vivo measurements, 863 calculations of midline dose were done, and the average deviation and ranges of its value were estimated. Data of 710 advanced larynx cancers were reviewed in order to achieve dose-response relationship. Patients data were fitted directly to L-Q model using maximum likelihood estimation. In 16.5% of measurements the deviation of midline dose was larger than -5.2%. A steep dose response relationship for TCP was found. Considering -5.2% deviation of 2 Gy fraction and 72 Gy of total dose, the 17% (from 48 to 31%) decrease of TCP was found. It shows that deviations of delivered dose influence the tumor control probability and that after systematic error finding during fractionated radiotherapy the value of remaining fraction size and total dose should be modified to compensate the change of TCP.

[Unconventional accelerated irradiation of advanced pharyngolaryngeal cancer as an alternative treatment compare to surgery. The interim results of randomized clinical trial]. / Przyspieszona niekonwencjonalna radioterapia zaawansowanego raka krtani i gardla dolnego jako alternatywa dla leczenia operacyjnego. Wczesne wyniki kontrolowanego doswiadczenia klinicznego.

The paper presents preliminary results (3 year tumour control and survival) of clinical randomized trial comparing accelerated fractionation (7 fx a week) with conventional (5 fx a week) radiotherapy (RT) for advanced pharyngo-laryngeal cancer. Significant treatment gain (p < 0.001) and good tolerance associated with accelerated RT was noted (82% of disease-free and 79% of overall survival). These results are similar with combined (total laryngectomy + postoperative RT) policy and, additionally, accelerated RT offers a high chance of larynx preservation.

[Radiotherapy of vertebral hemangiomas]. / Radioterapia naczyniaków trzonów kregów przebiegajacych z objawami bólowymi.

The paper presents the analysis of results of treatment with radiotherapy of 14 cases of vertebral hemangiomas. All patients were irradiated in accordance with conventional schedule fractionated doses, using 2 Gy per fraction. The total radiation dose amounted to 20 Gy (1 case), 24 Gy (4 cases) and 30 Gy (9 cases). The degree of pain relief and lesion reossification was assessed 1 months and 6 months after completion of radiotherapy. Complete pain relief 1 month post radiotherapy was noted in 5 cases (on average patients claimed that radiotherapy resulted in a 70% decrease of pain syndromes). Six months post radiotherapy complete pain relief was noted in 8 cases (on average patients reported a 90% decrease in pain). Signs of reossification were observed in cases 6 months after treatment. No correlation was noted neither between the degree of pain relief and reossification, nor between the total delivered dose and the degree of pain relief. The obtained results allow to conclude that conventionally fractionated radiotherapy (using 20-24 Gy as total dose) is a good method of analgetic treatment of vertebral hemangiomas probably based on the anti-inflammatory effect of radiation.

[Evaluation of severity and clinical course of acute mucosal reaction during postop radiotherapy of laryngeal cancer]. / Ocena nasilenia i przebiegu ostrego odczynu popromiennego blony sluzowej w trakcie pooperacyjnej radioterapii raka krtani.

In the group of 110 epiglottic and glottic cancer patients treated with postoperative radiotherapy, relationships between the severity of acute mucosal reaction and time of treatment for different types of surgery and for different intervals between surgery and postoperative radiotherapy were analysed. The dependence between the total dose and the radiation reaction was assigned. The maximal radiation reaction appeared in the fourth week of irradiation independently of operation type. The highest grade of reaction in the last week of irradiation appeared in the group after limited operations and the lowest one in the group after total laryngectomy. There was a statistically significant difference between distribution of acute radiation injury grade in a group after limited operation and a group after hemilaryngectomy compared by Wilcoxon matched pairs test. For the interval between operation and radiotherapy shorter than 6 weeks the highest reaction was in the fourth, for the interval 6 to 12 weeks in the third and for the interval longer than 22 weeks in the fifth week of irradiation. The highest reaction in the last irradiation week appeared in the first group, the lowest one in the second group. However, generally the time-interval between surgery and radiotherapy does not influence the severity of acute mucosal reaction (there was no statistically significant difference between reaction grade distribution compared by Wilcoxon matched pairs test). There was also no correlation between the total dose and intensity of radiation injury in last irradiation week. The interrelationships and other factors which could influence the obtained results were considered. The main final conclusions were formed: maximal intensity of mucous membrane radiation injury and the intensity in the last week of treatment depend on the character of previous operation (smaller operation--bigger postradiation reaction) and do not depend on total dose or on the interval between operation and beginning of radiotherapy.

Evaluation of delivered dose changes during radiation therapy.

The influence of changes in the thickness of the irradiated tissue block during radiotherapy on the error in dose delivery was assessed by dosimetry in vivo. In 55 cases of head and neck cancers, entrance and exit doses and the irradiated volume sizes were measured during the first and the twentieth fractions. The real and hypothetical midline doses (i.e. midline doses calculated when the entrance dose is considered as a planned one) were calculated. The average size of irradiated volume was smaller after 20 fractions. The mean of midline dose dosimetric errors during the twentieth fraction was larger (overdosage) than that during the first fraction. These means were compared and statistically significant differences were found. Our results confirm the value of in vivo dosimetry as an appropriate tool for detecting errors in delivered dose provoked by changes in irradiated volume dimensions and show the necessity to check irradiated volume thickness during the treatment.

[Treatment of giant cell tumor of bone: surgery or radiotherapy?]. / Leczenie guzów olbrzymiokomórkowych kosci--chirurgia czy radioterapia?

The results of treatment for giant cell tumor of bone in 41 patients subdivided into 4 groups have been assessed. In group treated with radical surgery (amputations, extensive excision) 100% patients were cured. In group treated with curettage alone success rate was 33.3% and in radiotherapy group--72.3%. Curettage and radiotherapy combined rendered 95% success rate and this mode of treatment should be recommended.