Curative high-dose reirradiation for patients with recurrent head and neck adenoid cystic carcinomas: outcomes and analysis of patterns of failure.

BACKGROUND: To investigate the outcomes of patients who underwent curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for unresectable recurrent or second primary head and neck adenoid cystic carcinoma (HNACC). METHODS: Ten patients, mostly KPS 90%, were reirradiated (3/10 with IMRT and 7/10 with PT) at a median maximum dose to the CTV of 64.2 Gy from July 2011 to November 2021. Locations at the time of reRT were mainly the sinus (4/10) and the salivary glands (including the parotid and submandibular gland, 3/10). CTCAEv5 was used to assess acute and late toxicities. Follow-up was the time between the end of reRT and the date of last news. RESULTS: The median time between the two irradiations was 53.5 months (IQR: 18-84). After a median follow-up of 26 months (range, 12.5-51.8 months), six patients had developed a locoregional recurrence (LR), of which four occurred within the previously irradiated volume. Two and three-year locoregional failure-free survival (LFFS) and overall survival (OS) were 55.6% [95%CI: 31-99.7%], and 41% [18.5-94%] and 66.7% [42-100%] and 44.4% [21.4-92.3%], respectively. LFFS and OS were significantly better in the subgroup of sinus tumors (p = .013) and the subgroup of patients re-irradiated more than two years after the first course of irradiation (p = .01). Seven patients had impairments before the start of reRT, including hearing impairment (3/10) and facial nerve impairment (3/10). The most severe late toxicities were brain necrosis (2/10), osteoradionecrosis (1/10) and vision decreased (1/10). CONCLUSION: Curative reRT for HNACC is possible for selected cases, but the LR rate in the irradiated field and the risk of severe toxicity remain high. Improved selection criteria and more carefully defined target volumes may improve outcome in these patients. A further study including larger cohort of patients would be useful to confirm these results.

Predictors of toxicity after curative reirradiation with intensity modulated radiotherapy or proton therapy for recurrent head and neck carcinoma: new dose constraints for pharyngeal constrictors muscles and oral cavity.

BACKGROUND: Our study aims to identify predictive factors of moderate to severe (grade ≥ 2) late toxicity after reirradiation (reRT) of recurrent head and neck carcinoma (HNC) and explore the correlations between dose organs at risk (OAR) and grade ≥ 2 toxicity. MATERIAL AND METHODS: Between 09/2007 and 09/2019, 55 patients were re-irradiated with IMRT or proton therapy with curative intent for advanced HNC. Our study included all patients for whom data from the first and second irradiations were available. Co-variables, including interval to reRT, size of re-irradiated PTV, and dose to OAR, were analyzed as potential predictors for developing moderate to severe long-term toxicity with death as a competing risk. Receiver-operator characteristics (ROC) analysis assessed the association between dose/volume parameters and the risk of toxicity. RESULTS: Twenty-three patients participated in our study. After a median follow-up of 41 months, 65% of the patients experienced grade ≥ 2 late toxicity. The average dose to pharyngeal constrictor muscles (PCM) at the time of reRT showed an association with the risk of grade ≥ 2 dysphagia: AUC = 0.78 (95% CI: 0.53-1), optimal cut-off value = 36.7 Gy (sensitivity 62%/specificity 100%). The average dose to the oral cavity at the time of reRT showed an association with the risk of grade ≥ 2 dysgeusia: AUC = 0.96 (0.89-1), optimal cut-off value = 20.5 Gy (sensitivity 100%/specificity 88%). CONCLUSION: Our analysis depicted an association between the dose to OAR and the risk of developing moderate to severe dysphagia and dysgeusia and proposed new dose constraints for PCM (36.7 Gy) and oral cavity (20.5 Gy).

Proton therapy and/or helical tomotherapy for locally advanced sinonasal skull base adenoid cystic carcinoma: Focus on experience of the Institut Curie and review of literature.

BACKGROUND: Sinonasal adenoid cystic carcinomas (SNACC) have high propensity for skull base (SB) infiltration. Unresectability or incomplete surgical resection in such cases make radiotherapy treatment paramount. Curative dose escalation is challenging because of adjacent organs at risk, especially in locally advanced cases. METHODS: Eighteen patients that had locally advanced SB SNACC with unresectable or incomplete surgical resection treated by proton therapy and/or helical tomotherapy at Institut Curie between 3/2010 and 8/2020 were retrospectively included. RESULTS: After median follow-up of 52 months, 5-year OS, LRRFS, DMFS, DFS rates were, respectively, 47% (95%CI: 26-83), 50% (95%CI: 36-88), 39% (95%CI: 26-81), 33% (95%CI: 22-73). One patient had grade 4 late optic nerve disorder. Eight patients had grade 3 late toxicity including mainly hearing impairments. CONCLUSION: Proton therapy and helical tomotherapy are effective and safe methods for curative dose escalation of locally advanced SB SNACC, which are a poor prognosis subgroup. Available literature suggests carbon-ion therapy could be an efficient alternative.

Curative high-dose reirradiation for patients with recurrent head and neck squamous cell carcinoma using IMRT or proton therapy: Outcomes and analysis of patterns of failure.

PURPOSE: To analyze outcomes of patients treated with curative reirradiation (reRT), with intensity-modulated radiation therapy (IMRT) or proton therapy (PT) for recurrent head and neck squamous cell carcinoma (HNSCC). MATERIALS: Among the 55 patients reirradiated for head and neck cancer from 30/08/2012 to 08/04/2019, 23 had HNSCC and received IMRT (52.2%) or PT (47.8%) at a median maximum dose to the CTV of 66 Gy. RESULTS: After a median follow-up of 41.3 months, 18 patients developed a locoregional recurrence (LR), of which eight (44.4%) occurred within the previously reirradiated volume. Two-year locoregional failure-free survival and overall survival were 18.3%[95%CI:7.1%-47.1%] and 42.5%[95%CI:26.2%-69.1%], respectively. Disease-free survival was significantly longer in the PT group (p = 0.031). Main late grade ≥2 toxicities were dysphagia and trismus. CONCLUSION: Curative reRT in HNSCC is possible for selected cases, but the LR rate in the irradiated field and the risk of toxicity grade ≥2 remain high.

Addressing the dosimetric impact of bone cement and vertebroplasty in stereotactic body radiation therapy.

PURPOSE: Bone cement used for vertebroplasty can affect the accuracy on the dose calculation of the radiation therapy treatment. In addition the CT values of high density objects themselves can be misrepresented in kVCT images. The aim of our study is then to propose a streamlined approach for estimating the real density of cement implants used in stereotactic body radiation therapy. METHODS: Several samples of cement were manufactured and irradiated in order to investigate the impact of their composition on the radiation dose. The validity of the CT conversion method for a range of photon energies was investigated, for the studied samples and on six patients. Calculations and measurements were carried out with various overridden densities and dose prediction algorithms (AXB with dose-to-medium reporting or AAA) in order to find the effective density override. RESULTS: Relative dose differences of several percent were found between the dose measured and calculated downstream of the implant using an ion chamber and TPS or EPID dosimetry. If the correct density is assigned to the implant, calculations can provide clinically acceptable accuracy (gamma criteria of 3%/2 mm). The use of MV imaging significantly favors the attribution of a correct equivalent density to the implants compared to the use of kVCT images. CONCLUSION: The porosity and relative density of the various studied implants vary significantly. Bone cement density estimations can be characterized using MV imaging or planar in vivo dosimetry, which could help determining whether errors in dose calculations are due to incorrect densities.

Out-of-field doses from radiotherapy using photon beams: A comparative study for a pediatric renal treatment.

PURPOSE: First, this experimental study aims at comparing out-of-field doses delivered by three radiotherapy techniques (3DCRT, VMAT (two different accelerators), and tomotherapy) for a pediatric renal treatment. Secondly, the accuracy of treatment planning systems (TPS) for out-of-field calculation is evaluated. METHODS: EBT3 films were positioned in pediatric phantoms (5 and 10 yr old). They were irradiated according to four plans: 3DCRT (Clinac 2100CS, Varian), VMAT (Clinac 2100CS and Halcyon, Varian), and tomotherapy for a same target volume. 3D dose determination was performed with an in-house Matlab tool using linear interpolation of film measurements. 1D and 3D comparisons were made between techniques. Finally, measurements were compared to the Eclipse (Varian) and Tomotherapy (Accuray) TPS calculations. RESULTS: Advanced radiotherapy techniques (VMATs and tomotherapy) deliver higher out-of-field doses compared to 3DCRT due to increased beam-on time triggered by intensity modulation. Differences increase with distance to target and reach a factor of 3 between VMAT and 3DCRT. Besides, tomotherapy delivers lower doses than VMAT: although tomotherapy beam-on time is higher than in VMAT, the additional shielding of the Hi-Art system reduces out-of-field doses. The latest generation Halcyon system proves to deliver lower peripheral doses than conventional accelerators. Regarding TPS calculation, tomotherapy proves to be suitable for out-of-field dose determination up to 30 cm from field edge whereas Eclipse (AAA and AXB) largely underestimates those doses. CONCLUSION: This study shows that the high dose conformation allowed by advanced radiotherapy is done at the cost of higher peripheral doses. In the context of treatment-related risk estimation, the consequence of this increase might be significative. Modern systems require adapted head shielding and a particular attention has to be taken regarding on-board imaging dose. Finally, TPS advanced dose calculation algorithms do not certify dose accuracy beyond field edges, and thus, those doses are not suitable for risk assessment.

High-dose proton therapy and tomotherapy for the treatment of sacral chordoma: a retrospective monocentric study.

OBJECTIVE: Radiation therapy (RT) is used for the treatment of sacral chordoma, in combination with surgery or alone for unresected tumours, to improve local control (LC) and potentially overall survival (OS). The purpose of the present study was to evaluate efficacy and toxicity of proton therapy (PT), and/or intensity modulated radiation therapy (IMRT), particularly Tomotherapy, for sacral chordoma treatment. Material: Between November 2005 and June 2018, 41 consecutive patients who were not included in clinical trials, received sacral chordoma radiation treatment in Institut Curie with Tomotherapy alone in 13 patients, and combined PT and Tomotherapy boost (Proton - Tomo) in 28 patients. RT was delivered as the exclusive local treatment in 11 patients, and as a post-operative complementary treatment in 30 patients. RESULTS: After a median follow-up of 46 months (range, 0-125 months), eight local relapses were observed, and seven patients developed distant metastasis (particularly bone and lung). The 2- and 5- year local relapse rates were 11.4% CI (0.65-22.2%) and 29% (10.5-47.4%), respectively. Over the follow-up period, ten patients died (24.4%). The estimated 2- and 5-year OS rates were 91.4% CI (82.5-100%) and 74.5% (59.4-93.5%), respectively. Fibrosis, cauda equina syndrome, and pain were the most common late toxicities. The comparison between Tomotherapy alone and Proton - Tomo revealed that acute and late cystitis were significantly more frequent in the Tomotherapy group: SHR = 0.12 IC95% (0.01-0.90 [p = .04]), as well as late proctitis. A dosimetric comparison confirmed the interest of PT to spare rectum and bladder in this context. CONCLUSION: RT remains essential to improve local control in sacral chordoma. The combination of proton and photon seems to improve organ at risk sparing, resulting in a decreased rate of reported late toxicities.

Evolution of radiation techniques in the treatment of mediastinal lymphoma: from 3D conformal radiotherapy (3DCRT) to intensity-modulated RT (IMRT) using helical tomotherapy (HT): a single-centre experience and review of the literature.

OBJECTIVE: To evaluate radiation techniques and their toxicity in the treatment of Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL) with mediastinal disease over a 10-year period. METHODS: Between 2003 and 2015, 173 patients with Stage I-III nodal lymphoma were treated in our institution: some of these patients were irradiated for HL or NHL with mediastinal disease. Some of the patients were treated by three-dimensional conformal radiotherapy (3DCRT), others by intensity-modulated radiotherapy (IMRT). RESULTS: We studied 26 males and 43 females with a median age of 26 years. The median follow-up was 43 months. 49 patients were treated by 3DCRT and 20 patients by IMRT. The median dose received by patients treated for NHL was 40 Gy (range: 36-44 Gy), and the median dose received by patients with HL was 30 Gy (range: 30-36 Gy). Between 2003 and 2006, 16 patients were treated by 3DCRT vs 0 patients by IMRT. Between 2007 and 2009, 16 patients received 3DCRT and one patient received IMRT. Between 2010 and 2015, 19 patients received IMRT, and no patients received 3DCRT. 11 of the 20 (55%) patients treated by IMRT and 35 of the 49 (71.4%) patients treated by 3DCRT experienced acute toxicity. Among the patients treated by 3DCRT, one patient experienced Grade 1 radiation pneumonitis and two patients experienced Grade 1 acute mucositis. No late toxicity was observed in patients treated by IMRT. CONCLUSION: Improvement of radiation techniques for HL and NHL appears to have improved acute and late clinical safety. Longer follow-up is necessary to evaluate very late toxicity. ADVANCES IN KNOWLEDGE: Improvement of radiation techniques for HL and NHL appears to improve the tolerance.

Implant breast reconstruction followed by radiotherapy: can helical tomotherapy become a standard irradiation treatment?

To evaluate the benefits and limitations of helical tomotherapy (HT) for loco-regional irradiation of patients after a mastectomy and immediate implant-based reconstruction. Ten breast cancer patients with retropectoral implants were randomly selected for this comparative study. Planning target volumes (PTVs) 1 (the volume between the skin and the implant, plus margin) and 2 (supraclavicular, infraclavicular, and internal mammary nodes, plus margin) were 50 Gy in 25 fractions using a standard technique and HT. The extracted dosimetric data were compared using a 2-tailed Wilcoxon matched-pair signed-rank test. Doses for PTV1 and PTV2 were significantly higher with HT (V95 of 98.91 and 97.91%, respectively) compared with the standard technique (77.46 and 72.91%, respectively). Similarly, the indexes of homogeneity were significantly greater with HT (p = 0.002). HT reduced ipsilateral lung volume that received ≥20 Gy (16.7 vs. 35%), and bilateral lungs (p = 0.01) and neighboring organs received doses that remained well below tolerance levels. The heart volume, which received 25 Gy, was negligible with both techniques. HT can achieve full target coverage while decreasing high doses to the heart and ipsilateral lung. However, the low doses to normal tissue volumes need to be reduced in future studies.

The role of helical tomotherapy in the treatment of bone plasmacytoma.

We evaluated the early clinical outcome of patients with solitary bone plasmacytoma (SP) or a solitary lesion of multiple myeloma (MM) treated with helical tomotherapy (HT) compared with 3D conformal radiotherapy (3D-CRT), in terms of target coverage and exposure of critical organs. Ten patients with SP and 3 patients with a solitary lesion of MM underwent radiation therapy (RT) delivered by HT, to a dose of 40 Gy in 20 fractions. Treatment planning was then performed with 3D-CRT and the dosimetric parameters of both techniques were compared. Patients were also assessed for response to treatment and acute toxicities. With a median follow-up of 13 months, 78% of patients with pain before RT had resolution of their symptoms. Coverage of target lesion was adequate with both techniques in 12 of 13 patients. Target coverage was significantly lower for HT (V(95%) = 98.55% vs. 97.15%; p = 0.04, for 3D-CRT and HT, respectively). Target overdoses were also lower with HT (V(105%) = 2.01% vs. 0.19%; p= 0.16), although nonsignificant. Finally, there were no significant differences in organs-at-risk irradiation between both techniques. The early treatment tolerance was excellent, with no toxicity higher than grade I. RT of SP and MM with a solitary lesion can be safely delivered with HT, with no major acute side effects and good symptomatic control. Finally, HT provides a dosimetry similar to that of 3D-CRT in terms of organs-at-risk sparing and target volume coverage.

Two-year clinical experience with tomotherapy: the French national cancer institute project on implementing new technology.

The pooled 2-year clinical experience using three tomotherapy units installed in France in 2007 is presented. Treatment indications and protocols were devised for each disease site and were the result of a consensus. A total of 642 patients were treated for central nervous system, head and neck, thoracic, abdominal, and pelvic tumors. Overall, grade 3, 4, and 5 acute toxicity was 10.7%, 0.3%, and 0.2%, respectively. Grade 3 chronic toxicity was 1.2%. There was no grade 4 or 5 chronic toxicity. The use of tomotherapy in a broad clinical practice is safe, and acute and chronic toxicity both are acceptable for all anatomical locations.

Helical tomotherapy for resected malignant pleural mesothelioma: dosimetric evaluation and toxicity.

This study evaluated adjuvant helical tomotherapy after extrapleural pneumonectomy ± neo-adjuvant chemotherapy in 24 patients with malignant pleural mesothelioma. Toxicity was judged acceptable despite 2 cases (8%) of suspected grade 5 pneumonitis. With a mean follow-up of 7 months, 5 patients had distant and 2 local and distant failure.

Mesothelioma at era of helical tomotherapy: results of two institutions in combining chemotherapy, surgery and radiotherapy.

PURPOSE: There is a scarce clinical experience about adjuvant helical tomotherapy (HT) in patients affected by malignant pleural mesothelioma (MPM) even though it appears as a useful technique to treat complex volume as the pleural cavity, and seems to have better dose distribution than the "classic" intensity modulated radiotherapy (IMRT). METHODS AND MATERIALS: Twenty-four patients received adjuvant radiotherapy (RT) by HT from August 1st, 2007 to December 1st, 2009 at Curie Institute (Paris) and René Gauducheau Cancer Center (Nantes). Thirteen patients had neoadjuvant chemotherapy. Extrapleural pleuropneumonectomy (EPP) was done in 23 patients. Median dose to PTV was 50Gy [48.7-55.9Gy] (2Gy/fraction). Acute and long term toxicities, disease free survival (DFS), overall survival (OS) and relapses are presented. RESULTS: Average follow up after RT was 7 months. The disease was staged mostly as T2-T3, N1-N2. Nineteen patients had epithelial type histology. Most patients tolerated radiotherapy with grade 1-2 side effects: redness of the skin, light cough or dyspnea, fatigue, nausea and odynophagia, mild increase of the post-operative thoracic pain. Grade 3 pneumonitis was suspected in 2 patients. Two grade 5 pneumonitis were also suspected. Eleven patients had a follow up of more than 6 months and no long term side effects related with HT were noted. At 24 months, 51.8% of patients were free of disease. Thirty percent of patients relapsed, with 2 patients presenting local relapses. Two patients died from recurrence. CONCLUSION: With limited follow up, HT has comparable toxicity to those observed with traditional IMRT. Higher radiation dose and good coverage results in excellent local control.

Early experience of helical tomotherapy for hepatobiliary radiotherapy.

Helical tomotherapy (HT), an image-guided, intensity-modulated, radiation therapy technique, allows for precise targeting while sparing normal tissues. We retrospectively assessed the feasibility and tolerance of the hepatobiliary HT in 9 patients. A total dose of 54 to 60 Gy was prescribed (1.8 or 2 Gy per fraction) with concurrent capecitabine for 7 patients. There were 1 hepatocarcinoma, 3 cholangiocarcinoma, 4 liver metastatic patients, and 1 pancreatic adenocarcinoma. All but one patient received previous therapies (chemotherapy, liver radiofrequency, and/or surgery). The median doses delivered to the normal liver and to the right kidney were 15.7 Gy and 4.4 Gy, respectively, below the recommended limits for all patients. Most of the treatment-related adverse events were transient and mild in severity. With a median followup of 12 months, no significant late toxicity was noted. Our results suggested that HT could be safely incorporated into the multidisciplinary treatment of hepatobiliary or pancreatic malignant disease.

Feasibility of helical tomotherapy for debulking irradiation before stem cell transplantation in malignant lymphoma.

PURPOSE: Preliminary clinical experience has suggested that radiation therapy (RT) may be effectively incorporated into conditioning therapy before transplant for patients with refractory/relapsed malignant lymphoma. We investigated the feasibility of debulking selective lymph node irradiation before autologous and/or allogeneic stem cell transplantation (SCT) using helical tomotherapy (HT). METHODS AND MATERIALS: Six consecutive patients with refractory malignant lymphoma were referred to our institution for salvage HT before SCT. All patients had been previously heavily treated but had bulky residual tumor despite chemotherapy (CT) intensification. Two patients had received previous radiation therapy. HT delivered 30-40 Gy in the involved fields (IF), using 6 MV photons, 2 Gy per daily fraction. Total duration of treatment was 28 to 35 days. RESULTS: Using HT, doses to critical organs (heart, lungs, esophagus, and parotids) were significantly decreased and highly conformational irradiation could be delivered to all clinical target volumes. HT delivery was technically possible, even in patients with lesions extremely difficult to irradiate in other conditions or in patients with previous radiation therapy. No Grade 2 or higher toxicity occurred. Four months after the end of HT, 5 patients experienced complete clinical, radiologic, and metabolic response and were subsequently referred for SCT. CONCLUSIONS: By more effectively sparing critical organs, HT may contribute to improving the tolerance of debulking irradiation before allograft. Quality of life may be preserved, and doses to the heart may be decreased. This is particularly relevant in heavily treated patients who are at risk for subsequent heart disease. These preliminary results require further prospective assessment.

Could helical tomotherapy do whole brain radiotherapy and radiosurgery?

Whole brain radiotherapy (WBRT) remains the standard management of breast cancer patients with brain metastases, allowing for symptomatic improvement and good local control in most patients. However, its results remain suboptimal in terms of both efficacy and toxicity. In highly selected breast cancer patients, stereotaxic radiotherapy demonstrates a very good local control with a low toxicity. With the purpose of improving the efficacy/toxicity ratio, we report the association of integrated boost with WBRT in a breast cancer patient with brain metastases. Two and a half years after completion of helical tomotherapy (HT), the patient experienced clinical and radiological complete remission of her brain disease. No delayed toxicity occurred and the patient kept her hair without need of radiosurgical procedure. The HT provided a high dosimetric homogeneity, delivering integrated radiation boosts, and avoiding critical structures involved in long-term neurological toxicity. Further assessment is required and recruitment of breast cancer patients into clinical trials is encouraged.

Preliminary experience of helical tomotherapy for locally advanced pancreatic cancer.

Radiotherapy for locally advanced pancreatic cancer is technically difficult and frequently associated with high-grade digestive toxicity. Helical tomotherapy (HT) is a new irradiation modality that combines megavoltage computed tomography imaging for patient positioning with intensity-modulated fan-beam radiotherapy. Its recent availability opens new fields of exploration for pancreatic radiotherapy as a result of its ability to tailor very well-defined dose distributions around the target volumes. Here, we report the use of HT in two patients with locally advanced pancreatic cancer. Doses to the bowel, kidneys and liver were reduced significantly, which allowed for excellent treatment tolerance without any high-grade adverse effects in either patient.

Solitary plasmocytoma: improvement in critical organs sparing by means of helical tomotherapy.

PURPOSE: Helical tomotherapy (HT) was assessed in two patients with paramedullar solitary bone plasmocytoma. We compared doses delivered to critical organs, according HT plan or tridimensional conformal plan. METHODS AND MATERIALS: One male (patient no. 1), 67 yr-old and one female (patient no. 2), 37-yr-old, with histologically, biologically and radiological confirmed paramedullar solitary plasmocytoma have been treated in our department between November 2007 and February 2008 using HT. The prescription dose was 40 Gy in 20 fractions. This HT treatment planning was compared with a routine dosimetric work that was executed for a standard conformal radiotherapy treatment planning. RESULTS: Treatment tolerance was excellent, without any side effects. Both patients achieved 9-month complete remission. HT resulted in substantial critical organs sparing. For patient no. 1, dose delivered to 20% of the total intestine volume was reduced from 28 Gy for conformal radiotherapy to 13 Gy for HT. Radiation dose delivered to 20% of the left kidney was reduced from 25 Gy to 7 Gy. For patient no. 2, volume of left lung that received at least 20 Gy was 12% for conformal radiotherapy vs. 6% for HT. CONCLUSIONS: For paramedullar solitary plasmocytoma, HT has the potential to significantly improve the quality of the dose distribution both in terms of better dose homogeneity within the planning target volume and more efficient sparing of critical organs.

Application of the quality index methodology for dosimetric verification of build-up effect beyond air-tissue interface in treatment planning system algorithms.

We have designed a simple benchmark test for the user of a treatment planning system to check the calculation algorithm's ability to model the build up effect beyond an air/tissue interface. The expected result is expressed as an inhomogeneity correction factor CF derived from measurements and from Monte Carlo calculations for a full range of photon beam qualities. The linear regression lines obtained from plotting CF as a function of beam quality index form the basis for a quantitative check of the algorithm performance.