Chest wall radiotherapy with volumetric modulated arcs and the potential role of flattening filter free photon beams

Purpose

The goal of the work was to assess the role of RapidArc treatments in chest wall irradiation after mastectomy and determine the potential benefit of flattening filter free beams.

Methods and material

Planning CT scans of 10?women requiring post-mastectomy chest wall radiotherapy were included in the study. A dose of 50?Gy in 2?Gy fractions was prescribed. Organs at risk (OARs) delineated were heart, lungs, contralateral breast, and spinal cord. Dose–volume metrics were defined to quantify the quality of concurrent treatment plans assessing target coverage and sparing of OARs. Plans were designed for conformal 3D therapy (3DCRT) or for RapidArc with double partial arcs (RA). RapidArc plans were optimized for both conventional beams as well as for unflattened beams (RAF). The goal for this planning effort was to cover 100% of the planning target volume (PTV) with ≥?90% of the prescribed dose and to minimize the volume inside the PTV receiving >?105% of the dose. The mean ipsilateral lung dose was required to be lower than 15?Gy and V_20?Gy?Results All techniques met planning objectives for PTV and for lung (3DCRT marginally failed for V_20?Gy). RA plans showed superiority compared to 3DCRT in the medium to high dose region for the ipsilateral lung. Heart irradiation was minimized by RAF plans with ~4.5?Gy and ~15?Gy reduction in maximum dose compared to RA and 3DCRT, respectively. RAF resulted in superior plans compared to RA with respect to contralateral breast and lung with a reduction of ~1.7?Gy and 1.0?Gy in the respective mean doses.

Conclusion

RapidArc treatment resulted in acceptable plan quality with superior ipsilateral tissue sparing compared to traditional techniques. Flattening filter free beams, recently made available for clinical use, might provide further healthy tissue sparing, particularly in contralateral organs, suggesting their applicability for large and complex targets.     

Moderately hypofractionated radiotherapy for localized prostate cancer

Purpose

To evaluate long-term outcome after dose-escalated, moderately hypofractionated radiotherapy for prostate cancer.

Methods

Since 2005, 150 consecutive patients were treated with primary radiotherapy for localized prostate cancer. Intensity modulated radiotherapy (IMRT) using the simultaneous integrated boost (SIB) technique was practiced in all patients and doses of 73.9 Gy (n?=?41) and 76.2 Gy (n?=?109) were delivered in 32 and 33 fractions, respectively. The pelvic lymph nodes were treated in 41 high-risk patients. Treatment was delivered using cone-beam CT based image-guided radiotherapy (IGRT). Toxicity was assessed prospectively using CTCAE 3.0; biochemical failure was defined according to the Phoenix definition of nadir +?2 ng/ml.

Results

Median follow-up of living patients was 50 months. Gastrointestinal (GI) toxicity was mild with >?80?% of the patients free from any GI toxicity during follow-up and no time trend to increased rates or to higher grade of GI toxicity. Two patients suffered from late grade 3 GI toxicity. Acute genitourinary (GU) toxicity grade 1–2 was observed in 85?% of the patients; most patients recovered quickly within 6 weeks after treatment. The rate of GU toxicity grade ≥?2 was <?10?% at 6–12 month but increased continuously to 22.4?% at 60 months; grade 3 GU toxicity remained below 5?% during follow-up. The 5-year freedom from biochemical failure (FFBF) was 82?% for all patients and 88, 80, and 78?% for low-, intermediate-, and high-risk disease.

Conclusion

Favorable FFBF with simultaneously low rates of toxicity was observed after moderately hypofractionated radiotherapy with 2 Gy-equivalent doses ≥?80 Gy. Conformal IMRT planning and accurate IGRT treatment delivery may have contributed to these results.     

Toxicity and outcome of pelvic IMRT for node-positive prostate cancer

Background and purpose

This study reports on the treatment techniques, toxicity, and outcome of pelvic intensity-modulated radiotherapy (IMRT) for lymph node-positive prostate cancer (LNPPC, T1-4, c/pN1 cM0).

Patients and methods

Pelvic IMRT to 45–50.4?Gy was applied in 39?cases either after previous surgery of involved lymph nodes (n?=?18) or with a radiation boost to suspicious nodes (n?=?21) with doses of 60–70?Gy, usually combined with androgen deprivation (n?=?37). The prostate and seminal vesicles received 70–74?Gy. In cases of previous prostatectomy, prostatic fossa and remnants of seminal vesicles were given 66–70?Gy. Treatment-related acute and late toxicity was graded according to the RTOG criteria.

Results

Acute radiation-related toxicity higher than ?grade?2 occurred in 2?patients (with the need for urinary catheter/subileus related to adhesions after surgery). Late toxicity was mild (grade 1–2) after a median follow-up of 70?months. Over 50% of the patients reported no late morbidity (grade 0). PSA control and cancer-specific survival reached 67% and 97% at over ?5?years.

Conclusion

Pelvic IMRT after the removal of affected nodes or with a radiation boost to clinically positive nodes led to an acceptable late toxicity (no grade 3/4 events), thus justifying further evaluation of this approach in a larger cohort.     

Physical and clinical implications of radiotherapy treatment of prostate cancer using a full bladder protocol

Purpose

To assess the dosimetric and clinical implication when applying the full bladder protocol for the treatment of the localized prostate cancer (PCA).

Patients and Methods

A total of 26 consecutive patients were selected for the present study. Patients underwent two series of CT scans: the day of the simulation and after 40 Gy. Each series consisted of two consecutive scans: (1) full bladder (FB) and (2) empty bladder (EB). The contouring of clinical target volumes (CTVs) and organs at risk (OAR) were compared to evaluate organ motion. Treatment plans were compared by dose distribution and dose?Cvolume histograms (DVH).

Results

CTV shifts were negligible in the laterolateral and superior?Cinferior directions (the maximum shift was 1.85 mm). Larger shifts were recorded in the anterior?Cposterior direction (95% CI, 0.83?C4.41 mm). From the dosimetric point of view, shifts are negligible: the minimum dose to the CTV was 98.5% (median; 95%CI, 95?C99%). The potential advantage for GU toxicity in applying the FB treatment protocol was measured: the ratio between full and empty bladder dose?Cvolume points (selected from our protocol) is below 0.61, excluding the higher dose region where DVHs converge.

Conclusion

Having a FB during radiotherapy does not affect treatment effectiveness, on the contrary it helps achieve a more favorable DVH and lower GU toxicities.     

Small bowel toxicity after high dose spot scanning-based proton beam therapy for paraspinal/retroperitoneal neoplasms

Purpose

Mesenchymal tumours require high-dose radiation therapy (RT). Small bowel (SB) dose constraints have historically limited dose delivery to paraspinal and retroperitoneal targets. This retrospective study correlated SB dose–volume histograms with side-effects after proton radiation therapy (PT).

Patients and methods

Between 1997 and 2008, 31 patients (mean age 52.1 years) underwent spot scanning-based PT for paraspinal/retroperitoneal chordomas (81?%), sarcomas (16?%) and meningiom (3?%). Mean total prescribed dose was 72.3 Gy (relative biologic effectiveness, RBE) delivered in 1.8–2 Gy (RBE) fractions. Mean follow-up was 3.8 years. Based on the pretreatment planning CT, SB dose distributions were reanalysed.

Results

Planning target volume (PTV) was defined as gross tumour volume (GTV) plus 5–7 mm margins. Mean PTV was 560.22 cm³. A mean of 93.2?% of the PTV was covered by at least 90?% of the prescribed dose. SB volumes (cm³) receiving doses of 5, 20, 30, 40, 50, 60, 70, 75 and 80 Gy (RBE) were calculated to give V5, V20, V30, V40, V50, V60, V70, V75 and V80 respectively. In 7/31 patients, PT was accomplished without any significant SB irradiation (V5?=?0). In 24/31 patients, mean maximum dose (Dmax) to SB was 64.1 Gy (RBE). Despite target doses of >?70 Gy (RBE), SB received >?50 and >?60 Gy (RBE) in only 61 and 54?% of patients, respectively. Mean SB volumes (cm³) covered by different dose levels (Gy, RBE) were: V20 (n?=?24): 45.1, V50 (n?=?19): 17.7, V60 (n?=?17): 7.6 and V70 (n?=?12): 2.4. No acute toxicity ≥ grade 2 or late SB sequelae were observed.

Conclusion

Small noncircumferential volumes of SB tolerated doses in excess of 60 Gy (RBE) without any clinically-significant late adverse effects. This small retrospective study has limited statistical power but encourages further efforts with higher patient numbers to define and establish high-dose threshold models for SB toxicity in modern radiation oncology.     

Comparative evaluation of CT-based and respiratory-gated PET/CT-based planning target volume (PTV) in the definition of radiation treatment planning in lung cancer: preliminary results

Purpose

The aim of this study was to compare planning target volume (PTV) defined on respiratory-gated positron emission tomography (PET)/CT (RG-PET/CT) to PTV based on ungated free-breathing CT and to evaluate if RG-PET/CT can be useful to personalize PTV by tailoring the target volume to the lesion motion in lung cancer patients.

Methods

Thirteen lung cancer patients (six men, mean age 70.0 years, 1 small cell lung cancer, 12 non-small cell lung cancer) who were candidates for radiation therapy were prospectively enrolled and submitted to RG-PET/CT. Ungated free-breathing CT images obtained during a PET/CT study were visually contoured by the radiation oncologist to define standard clinical target volumes (CTV1). Standard PTV (PTV1) resulted from CTV1 with the addition of 1-cm expansion of margins in all directions. RG-PET/CT images were contoured by the nuclear medicine physician and radiation oncologist according to a standardized institutional protocol for contouring gated images. Each CT and PET image of the patient’s respiratory cycle phases was contoured to obtain the RG-CT-based CTV (CTV2) and the RG-PET/CT-based CTV (CTV3), respectively. RG-CT-based and RG-PET/CT-based PTV (PTV2 and PTV3, respectively) were then derived from gated CTVs with a margin expansion of 7–8 mm in head to feet direction and 5 mm in anterior to posterior and left to right direction. The portions of gated PTV2 and PTV3 geometrically not encompassed in PTV1 (PTV2 out PTV1 and PTV3 out PTV1) were also calculated.

Results

Mean ± SD CTV1, CTV2 and CTV3 were 30.5?±?33.2, 43.1?±?43.2 and 44.8?±?45.2 ml, respectively. CTV1 was significantly smaller than CTV2 and CTV3 (p?=?0.017 and 0.009 with Student’s t test, respectively). No significant difference was found between CTV2 and CTV3. Mean ± SD of PTV1, PTV2 and PTV3 were 118.7?±?94.1, 93.8?±?80.2 and 97.0?±?83.9 ml, respectively. PTV1 was significantly larger than PTV2 and PTV3 (p?=?0.038 and 0.043 with Student’s t test, respectively). No significant difference was found between PTV2 and PTV3. Mean ± SD values of PTV2 out PTV1 and PTV3 out PTV1 were 12.8?±?25.4 and 14.3?±?25.9 ml, respectively. The percentage values of PTV2 out PTV1 and PTV3 out PTV1 were not lower than 10 % of PTV1 in 6/13 cases (46.2 %) and than 20 % in 3/13 cases (23.1 %).

Conclusion

Our preliminary data showed that RG-PET/CT in lung cancer can affect not only the volume of PTV but also its shape, as demonstrated by the assessment of gated PTVs outside standard PTV. The use of a gating technique is thus crucial for better delineating PTV by tailoring the target volume to the lesion motion in lung cancer patients.     

Tangential vs. defined radiotherapy in early breast cancer treatment without axillary lymph node dissection

Purpose

Recent studies have demonstrated low regional recurrence rates in early-stage breast cancer omitting axillary lymph node dissection (ALND) in patients who have positive nodes in sentinel lymph node dissection (SLND). This finding has triggered an active discussion about the effect of radiotherapy within this approach. The purpose of this study was to analyze the dose distribution in the axilla in standard tangential radiotherapy (SRT) for breast cancer and the effects on normal tissue exposure when anatomic level I–III axillary lymph node areas are included in the tangential radiotherapy field configuration.

Patients and methods

We prospectively analyzed the dosimetric treatment plans from 51 consecutive women with early-stage breast cancer undergoing radiotherapy. We compared and analyzed the SRT and the defined radiotherapy (DRT) methods for each patient. The clinical target volume (CTV) of SRT included the breast tissue without specific contouring of lymph node areas, whereas the CTV of DRT included the level I–III lymph node areas.

Results

We evaluated the dose given in SRT covering the axillary lymph node areas of level I–III as contoured in DRT. The mean V_D95?% of the entire level I–III lymph node area in SRT was 50.28?% (range, 37.31–63.24?%), V_D45 Gy was 70.1?% (54.8–85.4?%), and V_D40 Gy was 83.5?% (72.3–94.8?%). A significant difference was observed between lung dose and heart toxicity in SRT vs. DRT. The V_20 Gy and V_30 Gy of the right and the left lung in DRT were significantly higher in DRT than in SRT (p?<?0.001). The mean heart dose in SRT was significantly lower (3.93 vs. 4.72 Gy, p?=?0.005).

Conclusion

We demonstrated a relevant dose exposure of the axilla in SRT that should substantially reduce local recurrences. Furthermore, we demonstrated a significant increase in lung and heart exposure when including the axillary lymph nodes regions in the tangential radiotherapy field set-up.     

Intensity-modulated extended-field chemoradiation plus simultaneous integrated boost in the pre-operative treatment of locally advanced cervical cancer: a dose-escalation study

Objective:

To investigate the feasibility and determine the recommended pre-operative intensity-modulated radiotherapy (IMRT) dose of extended-field chemoradiation along with simultaneous integrated boost (SIB) dose escalation.

Methods:

A radiation dose of 40 Gy over 4 weeks, 2 Gy/fraction, was delivered to the tumour and the lymphatic drainage (planning target volume, PTV3), which encompassed a volume larger than standard (common iliac lymphatic area up to its apex, in front of the L3 vertebra), concurrently with chemotherapy (cisplatin and 5-fluorouracil). Radiation dose was escalated to the pelvis (PTV2) and to the macroscopic disease (PTV1) with the SIB-IMRT strategy. Three dose levels were planned: Level 1 (PTV3: 40/2 Gy; PTV2: 40/2 Gy; PTV1: 45/2.25 Gy), Level 2 (PTV3: 40/2 Gy; PTV2: 45/2.25 Gy; PTV1: 45/2.25 Gy) and Level 3 (PTV3: 40/2 Gy; PTV2: 45/2.25 Gy; PTV1: 50/2.5 Gy). All treatments were delivered in 20 fractions. Patients were treated in cohorts of between three and six per group using a Phase I study design. The recommended dose was exceeded if two of the six patients in a cohort experienced dose-limiting toxicity within 3 months from treatment.

Results:

19 patients [median age: 46 years; The International Federation of Gynecology and Obstetrics (FIGO) stage IB2: 3, IIB: 10, IIIA–IIIB: 6] were enrolled. Median follow-up was 24 months (9–60 months). The most common grade 3/4 toxicity was gastrointestinal (GI) (diarrhoea, mucous discharge, rectal/abdominal pain). At Levels 1 and 2, only one grade 3 GI toxicity per level was recorded, whereas at Level 3, two grade 3 GI toxicities (diarrhoea, emesis and nausea) were recorded.

Conclusion:

The SIB-IMRT technique was found to be feasible and safe at the recommended doses of 45 Gy to PTV1 and PTV2 and 40 Gy to PTV3 in the pre-operative treatment of patients with locally advanced cervical cancer. Unfortunately, this complex technique was unable to safely escalate dose beyond levels already achieved with three-dimensional conformal radiotherapy technique given acute GI toxicity.

Advances in knowledge:

A Phase I radiotherapy dose-escalation trial with SIB-IMRT technique is proposed in cervical cancer. This complex technique is feasible and safe at the recommended doses.     

Prospective phase II trial of cetuximab plus VMAT-SIB in locally advanced head and neck squamous cell carcinoma

Introduction

Cetuximab plus radiotherapy (RT) may be an effective alternative to chemoradiation in locally advanced head and neck squamous cell carcinoma (LASCCHN) patients. We analyzed a group of patients treated at our institute with cetuximab plus volumetric modulation arc therapy (VMAT) with the RapidArc technique in a simultaneous integrated boost (SIB) regime. The primary end point was the assessment of acute toxicity and the feasibility of the combined approach.

Materials and methods

Between December 2008 and March 2010, 22?patients were submitted to IMRT-SIB plus cetuximab for radical intent in case of LASCCHN. None of the patients was suitable for chemotherapy because of important comorbidities (the majority suffered of heart chronic diseases). All patients underwent planning CT (additional image modalities were acquired for contouring purposes in the same treatment position: MRI in 12 and FDG-PET in 4?out of 22?patients). VMAT, by means of RapidArc, and SIB with two dose levels of 54.45?Gy and 69.96?Gy in 33?fractions were adopted. All patients included in the analysis were concomitantly treated with cetuximab: administration of the drug was initiated 1?week before RT at a loading dose of 400?mg/m² body surface area over a period of 120?min, follow by a weekly 60?min infusion of 250 mg/m² for the duration of RT. Patients were assessed for toxicities according to the Radiation Therapy Oncology Group (RTOG) criteria.

Results

All but 2?patients completed treatment and achieved the minimum follow-up of 12?months after the end of the treatment. Of the 22?patients, 18% (4?patients) showed grade?1, 36% (8?patients) grade?2, and 36% (8?patients) showed grade?3 dermatitis, while 9% (2?patients) had grade?1, 36% (8?patients) grade?2, and 45% (10?patients) had grade?3 mucositis/stomatitis. No grade?4 toxicities were recorded. Considering blood parameters, 3?cases of grade?1 anemia and 1?case of grade?2 thrombocytopenia were observed. Nobody required feeding tube placement during treatment.

Conclusion

The here reported toxicity data are promising and encouraging in regard to the adoption of moderate hypofractionation with VMAT-SIB techniques, when cetuximab is concomitantly administered.     

Pelvic Ewing sarcomas

Purpose

The goal of the present work was to assess the potential advantage of intensity-modulated radiotherapy (IMRT) over three-dimensional conformal radiotherapy (3D-CRT) planning in pelvic Ewing’s sarcoma.

Patients and methods

A total of 8 patients with Ewing sarcoma of the pelvis undergoing radiotherapy were analyzed. Plans for 3D-CRT and IMRT were calculated for each patient. Dose coverage of the planning target volume (PTV), conformity and homogeneity indices, as well as further parameters were evaluated.

Results

The average dose coverage values for PTV were comparable in 3D-CRT and IMRT plans. Both techniques had a PTV coverage of V₉₅ >?98?% in all patients. Whereas the IMRT plans achieved a higher conformity index compared to the 3D-CRT plans (conformity index 0.79?±?0.12 vs. 0.54?±?0.19, p?=?0.012), the dose distribution across the target volumes was less homogeneous with IMRT planning than with 3D-CRT planning. This difference was statistically significant (homogeneity index 0.11?±?0.03 vs. 0.07?±?0.0, p?=?0.035). For the bowel, D_mean and D_1%, as well as V₂ to V₆₀ were reduced in IMRT plans. For the bladder and the rectum, there was no significant difference in D_mean. However, the percentages of volumes receiving at least doses of 30, 40, 45, and 50 Gy (V₃₀ to V₅₀) were lower for the rectum in IMRT plans. The volume of normal tissue receiving at least 2 Gy (V₂) was significantly higher in IMRT plans compared with 3D-CRT, whereas at high dose levels (V₃₀) it was significantly lower.

Conclusion

Compared to 3D-CRT, IMRT showed significantly better results regarding dose conformity (p?=?0.012) and bowel sparing at dose levels above 30 Gy (p?=?0.012). Thus, dose escalation in the radiotherapy of pelvic Ewing’s sarcoma can be more easily achieved using IMRT.     

Hyperfractionated accelerated radiotherapy with concomitant integrated boost of 70–75?Gy in 5?weeks for advanced head and neck cancer

Background and purpose

The present study was performed to evaluate the feasibility of a new, 5-week regimen of 70–75?Gy hyperfractionated accelerated radiotherapy with concomitant integrated boost (HARTCIB) for locally advanced, inoperable head and neck cancer.

Methods and materials

A total of 39?patients with very advanced, stage?IV nonmetastatic head and neck squamous cell carcinoma (median gross tumor volume 72?ml) were included in this phase?I dose escalation study. A total of 50?fractions intensity-modulated radiotherapy (IMRT) were administered twice daily over 5?weeks. Prescribed total dose/dose per fraction for planning target volume (PTV_tumor) were 70?Gy in 1.4?Gy fractions, 72.5?Gy in 1.45?Gy fractions, and 75?Gy in 1.5?Gy fractions for 10, 13, and 16?patients, respectively. Uninvolved lymphatic nodes (PTV_uninvolved) were irradiated with 55?Gy in 1.1?Gy fractions using the concomitant integrated boost.

Results

Acute toxicity was evaluated according to the RTOG/EORTC scale; the incidence of grade?3 mucositis was 51% in the oral cavity/pharynx and 0% in skin and the recovery time was ≤?9?weeks for all patients. Late toxicity was evaluated in patients in complete remission according to the RTOG/EORTC scale. No grade?3/4 late toxicity was observed. The 1-year locoregional progression-free survival was 50% and overall survival was 55%.

Conclusion

HARTCIB (75?Gy in 5?weeks) is feasible for patients deemed unsuitable for chemoradiation. Acute toxicity was lower than predicted from radiobiological models; duration of dysphagia and confluent mucositis were particularly short. Better conformity of radiotherapy allows the use of more intensive altered fractionation schedules compared with older studies. These results suggest that further dose escalation might be possible when highly conformal techniques (e.g., stereotactic radiotherapy) are used.     

RapidArc combined with the active breathing coordinator provides an effective and accurate approach for the radiotherapy of hepatocellular carcinoma

Purpose

The goal of this research was to investigate the feasibility of volumetric modulated arc therapy, RapidArc (RA), in association with the active breathing coordinator (ABC) for the treatment of hepatocellular carcinoma (HCC) with radiotherapy.

Patients and materials

A total of 12?patients with HCC, after receiving transcatheter arterial chemoembolization (TACE) treatment, underwent three-dimensional computer tomography (3D-CT) scanning associated with ABC using end inspiration hold (EIH), end expiration hold (EEH), and free breathing (FB) techniques. The three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and RA plans (three 135° arcs) were designed on different CT images, respectively. The liver volume, gross tumor volume (GTV), and planning target volume (PTV) of the three breath status and the dosimetric differences of the different plans were compared.

Results

There were no significant differences in the volumes of live and GTV between the three breathing techniques (p?>?0.05); the PTV in FB was greater than in the EEH and EIH (p?20, V₃₀, and V₄₀ of normal liver compared to 3D-CRT, while the V₅ and V₁₀ in RA were higher than in IMRT. The mean values in mean dose, V₁₀, V₂₀, V₃₀, and V₄₀ of the normal liver were reduced from 13.12?Gy, 46%, 24%, 13%, and 8% in RA_FB to 10.23?Gy, 35%, 16%, 8%, and 5% in RA_EEH and 9.23?Gy, 32%, 16%, 8%, and 5% in RA_EIH?, respectively. In addition, the treatment time of RA was equal to 3D-CRT, which was significantly shorter than IMRT.

Conclusion

RA in conjunction with ABC for the treatment of HCC with radiotherapy can achieve better dose delivery and ensure the accuracy of the target volume, which spares more organs at risk, uses fewer monitor units, and shortens treatment time.     

Long-term results of total body irradiation in adults with acute lymphoblastic leukemia

Purpose

The aim of this chart review of adult patients treated for acute lymphoblastic leukemia (ALL) with total body irradiation (TBI) was to evaluate early and late toxicity and long-term outcome.

Patients and methods

A total of 110 adult patients (34?±?12 years) with ALL underwent TBI (6?fractions of ?2 Gy for a total of 12 Gy) as a part of the treatment regimen before transplantation. Treatment-related toxicity, mortality, and hematologic outcome are reported.

Results

Mean follow-up was 70 months. The 2- and 5-year leukemia-free survival rates were 78 and 72?%, respectively. In all, 29?% (32/110) patients suffered from medullary recurrence after a median time of 7 months. Gender was the only statistically significant prognostic factor in terms of overall survival in favor of female patients. Treatment-related mortality and overall survival after 2 and 5 years were 16 and 22?%, and 60 and 52.7?%, respectively. The most frequent late reaction wascGVHD of the skin (n?=?33, 30?%). In addition, 15.5?% (17/110 patients) suffered pulmonary symptoms, and 6 patients developed lung fibrosis. Eyes were frequently affected by the radiation (31/110?=?28?%); 12 of 110 patients (11?%) presented with symptoms from osteoporosis, 5 of 110 patients (4.5?%) developed hypothyreosis and 2 patients diabetes mellitus. Of the male patients, 11?% reported erectile dysfunction or loss of libido, while 2 of 36 women reported menopausal syndrome at the mean time of 28 months after treatment with requirement for substitution. No women became pregnant after treatment. No acute or late cardiac toxicities were documented in our patients. No secondary malignancies were documented.

Conclusion

Although hematologic outcome was in the upper range of that reported in the literature, treatment-related mortality (TRM) and medullary recurrences remain a challenge. Sophisticated radiation techniques allow for decreasing toxicity to certain organs and/or dose escalation to the bone marrow in highly selected patients in order to improve therapeutic breadth.     

Can treatment of pediatric Hodgkin’s lymphoma be improved by PET imaging and proton therapy?

Background and purpose

To explore a new positron emission tomography (PET)-based target concept for pediatric Hodgkin’s lymphoma (PHL).

Patients and methods

For 10 patients, the planning target volume PTV1 was based on initial CT tumor extension and PTV2 on anatomy-related PET-positive lymph node levels after chemotherapy. The treatment techniques investigated (prescribed dose 19.8 Gy) comprised opposed-field (2F), intensity-modulated photon (IMXT), and single-field (PS) proton techniques. Treatment concepts were compared concerning dose-volume histogram (DVH) parameters and organ-equivalent doses (OED).

Results

The median PTV1 and PTV2 were 902?±?555 cm³ and 281?±?228 cm³. When using PTV2 instead of PTV1 for all techniques, the D_2% of the heart was reduced from 14 to 9 Gy and the D_mean of the thyroid from 16.6 to 2.7 Gy. Low- (20%), median- (50%), and high-dose volumes (80%) were reduced by 60% for the heart and bones using PTV2. PS reduced the high-dose volume of the lungs and the heart by up to 60%. IMXT increased the low-dose volumes and OED. PTV2 reduced OED by 54?±?10% for all organs at risk.

Conclusion

PTV2 has a high impact on the treated volume and on sparing of organs at risk. The combination of an adaptive target volume definition with protons could contribute to future PHL treatment concepts.     

Quasi-VMAT in high-grade glioma radiation therapy

Purpose

To compare a quasi-volumetric modulated arc therapy (qVMAT) with three-dimensional conformal radiation therapy (3D-CRT) and intensity-modulated radiation therapy (IMRT) for the treatment of high-grade gliomas. The qVMAT technique is a fast method of radiation therapy in which multiple equispaced beams analogous to those in rotation therapy are radiated in succession.

Patients and methods

This study included 12 patients with a planning target volume (PTV) that overlapped at least one organ at risk (OAR). 3D-CRT was planned using 2–3 non-coplanar beams, whereby the field-in-field technique (FIF) was used to divide each field into 1–3 subfields to shield the OAR. The qVMAT strategy was planned with 15 equispaced beams and IMRT was planned using 9 beams with a total of 80 segments. Inverse planning for qVMAT and IMRT was performed by direct machine parameter optimization (DMPO) to deliver a homogenous dose distribution of 60 Gy within the PTV and simultaneously limit the dose received by the OARs to the recommended values. Finally, the effect of introducing a maximum dose objective (max. dose <?54 Gy) for a virtual OAR in the form of a 0.5 cm ring around the PTV was investigated.

Results

The qVMAT method gave rise to significantly improved PTV_95% and conformity index (CI) values in comparison to 3D-CRT (PTV_95%?=?90.7?% vs. 82.0?%; CI?=?0.79 vs. 0.74, respectively). A further improvement was achieved by IMRT (PTV_95%?=?94.4?%, CI?=?0.78). In qVMAT and IMRT, the addition of a 0.5 cm ring around the PTV produced a significant increase in CI (0.87 and 0.88, respectively), but dosage homogeneity within the PTV was considerably reduced (PTV_95%?=?88.5?% and 92.3?%, respectively). The time required for qVMAT dose delivery was similar to that required using 3D-CRT.

Conclusion

These findings suggest that qVMAT should be preferred to 3D-CRT for the treatment of high-grade gliomas. The qVMAT method could be applied in hospitals, for example, which have limited departmental resources and are not equipped with systems capable of VMAT delivery.     

Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer

Objective:

The aim of this study was to evaluate the potential of simultaneously modulated accelerated radiation therapy (SMART) to reduce the incidence of severe acute oesophagitis in the treatment of unresectable locally advanced non-small-cell lung cancer (LANSCLC).

Methods:

21 patients were treated with SMART and concomitant platinum-based chemotherapy. The prescribed doses were limited to 54 Gy at 1.8 Gy per day to the zones of presumed microscopic extent while simultaneously maintaining doses of 66 Gy at 2.2 Gy per day to the macroscopic disease. The whole treatment was delivered over 30 fractions and 6 weeks. Dosimetric parameters of SMART and the standard technique of irradiation [intensity-modulated radiation therapy (IMRT)] were compared. Acute toxicity was prospectively recorded.

Results:

The highest grade of oesophagitis was 62% (13 patients) grade 1, 33% (7 patients) grade 2 and 5% (1 patient) grade 3. Three (14%) patients experienced acute grade 2 pneumonitis. There was no grade 4 oesophageal or pulmonary toxicity. Doses to the organs at risk were significantly reduced in SMART compared with IMRT [oesophagus: V_50Gy, 28.5 Gy vs 39.9 Gy (p = 0.003); V_60Gy, 7.1 Gy vs 30.7 Gy (p = 0.003); lung: V_20Gy, 27.4 Gy vs 30.1 Gy (p = 0,002); heart: V_40Gy, 7.3 Gy vs 10.7 Gy (p = 0.006); spine: D_max, 42.4 Gy vs 46.4 Gy (p = 0.003)]. With a median follow-up of 18 months (6–33 months), the 1-year local control rate was 70% and the disease-free survival rate was 47%.

Conclusion:

SMART reduces the incidence of severe oesophagitis and improves the whole dosimetric predictors of toxicity for the lung, heart and spine.

Advances in knowledge:

Our study shows that SMART optimizes the therapeutic ratio in the treatment of LANSCLC, opening a window for dose intensification.     

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

Backgroud

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

Patients and methods

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

Results

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

Conclusion

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