Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

Treatment of loco-regional recurrence of nasopharyngeal carcinoma in a non-endemic area: oncologic outcomes, morbidity, and proposal of a prognostic nomogram.

Introduction: The study assessed outcomes and toxicities of different treatment modalities for local and/or regional recurrent nasopharyngeal carcinoma (NPC) in a non-endemic area. Methods: Patients treated with curative intent for recurrent NPC with salvage surgery, photon-based radiotherapy, proton therapy (PT), with or without chemotherapy, at different Italian referral centers between 1998 and 2020 were included. Adverse events and complications were classified according to the Common Terminology Criteria for Adverse Events. Characteristics of the patients, tumors, treatments, and complications are presented along with uni- and multivariate analysis of prognostic factors. A survival predictive nomogram is also provided. Results: A total of 140 patients treated from 1998 to 2020 were retrospectively assessed. Cases with lower age, comorbidity rate, stage, and shorter disease-free interval (DFI) preferentially underwent endoscopic surgery. More advanced cases underwent re-irradiation, fairly distributed between photon-based radiotherapy and PT. Age and DFI were independent factors influencing overall survival. No independent prognostic effect of treatment modality was observed. No significant difference in the morbidity profile of treatments was observed, with 40% of patients experiencing at least one adverse event classified as G3 or higher. Conclusion: Recurrent NPC in a non-endemic area has dissimilar aspects compared to its endemic counterpart, suggesting the need for further studies that can guide the choice of the best treatment modality.

Does variable RBE affect toxicity risks for mediastinal lymphoma patients? NTCP-based evaluation after proton therapy treatment.

INTRODUCTION: Mediastinal lymphoma (ML) is a solid malignancy affecting young patients. Modern combined treatments allow obtaining good survival probability, together with a long life expectancy, and therefore with the need to minimize treatment-related toxicities. We quantified the expected toxicity risk for different organs and endpoints in ML patients treated with intensity-modulated proton therapy (IMPT) at our centre, accounting also for uncertainties related to variable RBE. METHODS: Treatment plans for ten ML patients were recalculated with a TOPAS-based Monte Carlo code, thus retrieving information on LET and allowing the estimation of variable RBE. Published NTCP models were adopted to calculate the toxicity risk for hypothyroidism, heart valve defects, coronary heart disease and lung fibrosis. NTCP was calculated assuming both constant (i.e. 1.1) and variable RBE. The uncertainty associated with individual radiosensitivity was estimated by random sampling α/ß values before RBE evaluation. RESULTS: Variable RBE had a minor impact on hypothyroidism risk for 7 patients, while it led to significant increase for the remaining three (+24% risk maximum increase). Lung fibrosis was slightly affected by variable RBE, with a maximum increase of â‰… 1%. This was similar for heart valve dysfunction, with the exception of one patient showing an about 10% risk increase, which could be explained by means of large heart volume and D1 increase. DISCUSSION: The use of NTCP models allows for identifying those patients associated with a higher toxicity risk. For those patients, it might be worth including variable RBE in plan evaluation.

Custom-Made 3D-Printed Implants for Anterior Column Reconstruction in the Upper Cervical Spine after Intralesional Extracapsular Excision-Report of 2 Cases and Literature Review.

The use of three-dimensional (3D)-printed custom-made implants is spreading in the orthopedics field for the reconstruction of bone losses or for joint replacement, thanks to their unparalleled versatility. In particular, this novel technology opens new perspectives to formulate custom-made fixation strategies for the upper cervical region, sacrum and pelvis, where reconstruction is challenging. We report and analyze the literature concerning upper cervical reconstruction with 3D-printed personalized implants after tumor surgery, and discuss two cases of patients where this technology was used to reconstruct the anterior column after extracapsular debulking of C2 recurrent chordoma at our institution.

Proton therapy in the treatment of hepatocellular carcinoma.

Liver cancer represents one of the most common causes of death from cancer worldwide. Hepatocellular carcinoma (HCC) accounts for 90% of all primary liver cancers. Among local therapies, evidence regarding the use of radiation therapy is growing. Proton therapy currently represents the most advanced radiation therapy technique with unique physical properties which fit well with liver irradiation. Here, in this review, we aim to 1) illustrate the rationale for the use of proton therapy (PT) in the treatment of HCC, 2) discuss the technical challenges of advanced PT in this disease, 3) review the major clinical studies regarding the use of PT for HCC, and 4) analyze the potential developments and future directions of PT in this setting.

Toxicity and Clinical Results after Proton Therapy for Pediatric Medulloblastoma: A Multi-Centric Retrospective Study.

Medulloblastoma is the most common malignant brain tumor in children. Even if current treatment dramatically improves the prognosis, survivors often develop long-term treatment-related sequelae. The current radiotherapy standard for medulloblastoma is craniospinal irradiation with a boost to the primary tumor site and to any metastatic sites. Proton therapy (PT) has similar efficacy compared to traditional photon-based radiotherapy but might achieve lower toxicity rates. We report on our multi-centric experience with 43 children with medulloblastoma (median age at diagnosis 8.7 years, IQR 6.6, M/F 23/20; 26 high-risk, 14 standard-risk, 3 ex-infant), who received active scanning PT between 2015 and 2021, with a focus on PT-related acute-subacute toxicity, as well as some preliminary data on late toxicity. Most acute toxicities were mild and manageable with supportive therapy. Hematological toxicity was limited, even among HR patients who underwent hematopoietic stem-cell transplantation before PT. Preliminary data on late sequelae were also encouraging, although a longer follow-up is needed.

Multicomponent T2 relaxometry reveals early myelin white matter changes induced by proton radiation treatment.

PURPOSE: To investigate MRI myelin water imaging (MWI) by multicomponent T2 relaxometry as a quantitative imaging biomarker for brain radiation-induced changes and to compare it with DTI. METHODS: Sixteen patients underwent fractionated proton therapy (PT) receiving dose to the healthy tissue because of direct or indirect (base skull tumors) irradiation. MWI was performed by a multi-echo sequence with 32 equally spaced echoes (10-320 ms). Decay data were processed to identify 3 T2 compartments: myelin water (Mw) below 40 ms, intra-extracellular water (IEw) between 40 and 250 ms, and free water (CSFw) above 250 ms. Both MWI and DTI scans were acquired pre (pre)-treatment and immediately at the end (end) of PT. After image registration, voxel-wise difference maps, obtained by subtracting MWI and DTI pre from those acquired at the end of PT, were compared with the corresponding biological equivalent dose (BED). RESULTS: Mw difference showed a positive correlation and IEw difference showed a negative correlation with BED considering end-pre changes (P < .01). The changes in CSFw were not significantly correlated with the delivered BED. The changes in DTI data, considering end-pre acquisitions, showed a positive correlation between fractional anisotropy and the delivered BED. CONCLUSION: MWI might detect early white matter radiation-induced alterations, providing additional information to DTI, which might improve the understanding of the pathogenesis of the radiation damage.

Accurate proton treatment planning for pencil beam crossing titanium fixation implants.

PURPOSE: To present a planning strategy for proton pencil-beam scanning when titanium implants need to be crossed by the beam. METHODS: We addressed three issues: the implementation of a CT calibration curve to assign to titanium the correct stopping power; the effect of artefacts on CT images and their reduction by a dedicated algorithm; the differences in dose computation depending on the dose engine, pencil-beam vs Monte-Carlo algorithms. We performed measurement tests on a simple cylinder phantom and on a real implant. These phantoms were irradiated with three geometries (single spots, uniform mono-energetic layer and uniform box), measuring the exit dose either by radio-chromic film or multi-layer ionization chamber. The procedure was then applied on two patients treated for chordoma. RESULTS: We had to set in the calibration curve a mass density equal to 4.37 g/cm3 to saturated Hounsfield Units, in order to have the correct stopping power assigned to titanium in TPS. CT artefact reduction algorithm allowed a better reconstruction of the shape and size of the implant. Monte-Carlo resulted accurate in computing the dose distribution whereas the pencil-beam algorithm failed due to sharp density interfaces between titanium and the surrounding material. Finally, the treatment plans obtained on two patients showed the impact of the dose engine algorithm, with 10-20% differences between pencil-beam and Monte-Carlo in small regions distally to the titanium screws. CONCLUSION: The described combination of CT calibration, artefacts reduction and Monte-Carlo computation provides a reliable methodology to compute dose in patients with titanium implants.

The Role of Plan Robustness Evaluation in Comparing Protons and Photons Plans - An Application on IMPT and IMRT Plans in Skull Base Chordomas.

PURPOSE: To analyze robustness of treatment plans optimized using different approaches in intensity modulated proton therapy (IMPT) and investigate the necessity of robust optimization and evaluation in intensity modulated radiotherapy (IMRT) plans for skull base chordomas. MATERIALS AND METHODS: Two photon plans, standard IMRT and robustly optimized IMRT (RB-IMRT), and two IMPT plans, robustly optimized multi field optimization (MFO) and hybrid-MFO (HB-MFO), were created in RayStation TPS for five patients previously treated using single field uniform optimization (SFO). Both set-up and range uncertainties were incorporated during robust optimization of IMPT plans whereas only set-up uncertainty was used in RB-IMRT. The dosimetric outcomes from the five planning techniques were compared for every patient using standard dose volume indices and integral dose (ID) estimated for target and organs at risk (OARs). Robustness of each treatment plan was assessed by introducing set-up uncertainties of ±3 mm along the three translational axes and, only in protons, an additional range uncertainty of ±3.5%. RESULTS: All the five nominal plans provided comparable and clinically acceptable target coverage. In comparison to nominal plans, worst case decrease in D95% of clinical target volume-high risk (CTV-HR) were 11.1%, 13.5%, and 13.6% for SFO, MFO, and HB-MFO plans respectively. The corresponding values were 13.7% for standard IMRT which improved to 11.5% for RB-IMRT. The worst case increased in high dose (D1%) to CTV-HR was highest in IMRT (2.1%) and lowest in SFO (0.7%) plans. Moreover, IMRT showed worst case increases in D1% for all neurological OARs and were lowest for SFO plans. The worst case D1% for brainstem, chiasm, spinal cord, optic nerves, and temporal lobes were increased by 29%, 41%, 30%, 41% and 14% for IMRT and 18%, 21%, 21%, 24%, and 7% for SFO plans, respectively. In comparison to IMRT, RB-IMRT improved D1% of all neurological OARs ranging from 5% to 14% in worst case scenarios. CONCLUSION: Based on the five cases presented in the current study, all proton planning techniques (SFO, MFO and HB-MFO) were robust both for target coverage and OARs sparing. Standard IMRT plans were less robust than proton plans in regards to high doses to neurological OARs. However, robust optimization applied to IMRT resulted in improved robustness in both target coverage and high doses to OARs. Robustness evaluation may be considered as a part of plan evaluation procedure even in IMRT.

Clinical implementation in proton therapy of multi-field optimization by a hybrid method combining conventional PTV with robust optimization.

To implement a robust multi-field optimization (MFO) technique compatible with the application of a Monte Carlo (MC) algorithm and to evaluate its robustness. Nine patients (three brain, five head-and-neck, one spine) underwent proton treatment generated by a novel robust MFO technique. A hybrid (hMFO) approach was implemented, planning dose coverage on isotropic PTV compensating for setup errors, whereas range calibration uncertainties are incorporated into PTV robust optimization process. hMFO was compared with single-field optimization (SFO) and full robust multi-field optimization (fMFO), both on the nominal plan and the worst-case scenarios assessed by robustness analysis. The SFO and the fMFO plans were normalized to hMFO on CTV to obtain iso-D95 coverage, and then the organs at risk (OARs) doses were compared. On the same OARs, in the normalized nominal plans the potential impact of variable relative biological effectiveness (RBE) was investigated. hMFO reduces the number of scenarios computed for robust optimization (from twenty-one in fMFO to three), making it practicable with the application of a MC algorithm. After normalizing on D95 CTV coverage, nominal hMFO plans were superior compared to SFO in terms of OARs sparing (p  < 0.01), without significant differences compared to fMFO. The improvement in OAR sparing with hMFO with respect to SFO was preserved in worst-case scenarios (p  < 0.01), confirming that hMFO is as robust as SFO to physical uncertainties, with no significant differences when compared to the worst case scenarios obtained by fMFO. The dose increase on OARs due to variable RBE was comparable to the increase due to physical uncertainties (i.e. 4-5 Gy(RBE)), but without significant differences between these techniques. hMFO allows improving plan quality with respect to SFO, with no significant differences with fMFO and without affecting robustness to setup, range and RBE uncertainties, making clinically feasible the application of MC-based robust optimization.

Harmonization of proton treatment planning for head and neck cancer using pencil beam scanning: first report of the IPACS collaboration group.

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer.Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created.Results: For CTV1, the average Dmedian was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average Dmedian was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams.Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.

Radiation-Induced Moyamoya Syndrome After Proton Therapy in Child with Clival Chordoma: Natural History and Surgical Treatment.

BACKGROUND: Proton therapy has proven to be effective and safe in the treatment of radioresistant skull base tumors such as chordomas. Thanks to the peculiar physical properties of the proton beam, radiation energy is delivered in a narrow space called the Bragg peak and the surrounding normal tissues receive a minimal amount of the radiation dose. This is important to lower the risk of radiation-induced damage, especially in children. However, local adverse effects in proximity to the target volume may occur. In particular, the development of moyamoya syndrome (MMS) has been rarely reported in children receiving proton beam therapy for brain tumors. CASE DESCRIPTION: We report on a child who developed rapidly progressive MMS after proton beam therapy for a clivus chordoma. A combined indirect revascularization procedure by encephalo-duro-arterio-synangiosis and encephalo-myo-synangiosis was performed with good neuroradiologic and clinical outcome. CONCLUSIONS: Regardless of the presence of known risk factors for MMS, strict neuroimaging surveillance is indicated in all patients treated with radiotherapy including those receiving proton beam therapy. We suggest that an early revascularization procedure should be considered in patients with worsening symptoms and/or sign of neuroradiologic progression of cerebral vasculopathy. This management of MMS could lower the risk of permanent neurologic deficits and improve patients' quality of life.

Single-energy intensity modulated proton therapy.

In this note, an intensity modulated proton therapy (IMPT) technique, based on the use of high single-energy (SE-IMPT) pencil beams, is described.The method uses only the highest system energy (226 MeV) and only lateral penumbra to produce dose gradient, as in photon therapy. In the study, after a preliminary analysis of the width of proton pencil beam penumbras at different depths, SE-IMPT was compared with conventional IMPT in a phantom containing titanium inserts and in a patient, affected by a spinal chordoma with fixation rods.It was shown that SE-IMPT has the potential to produce a sharp dose gradient and that it is not affected by the uncertainties produced by metal implants crossed by the proton beams. Moreover, in the chordoma patient, target coverage and organ at risk sparing of the SE-IMPT plan resulted comparable to that of the less reliable conventional IMPT technique. Robustness analysis confirmed that SE-IMPT was not affected by range errors, which can drastically affect the IMPT plan.When accepting a low-dose spread as in modern photon techniques, SE-IMPT could be an option for the treatment of lesions (e.g. cervical bone tumours) where steep dose gradient could improve curability, and where range uncertainty, due for example to the presence of metal implants, hampers conventional IMPT.

Systematic evaluation of three different commercial software solutions for automatic segmentation for adaptive therapy in head-and-neck, prostate and pleural cancer.

PURPOSE: To validate, in the context of adaptive radiotherapy, three commercial software solutions for atlas-based segmentation. METHODS AND MATERIALS: Fifteen patients, five for each group, with cancer of the Head&Neck, pleura, and prostate were enrolled in the study. In addition to the treatment planning CT (pCT) images, one replanning CT (rCT) image set was acquired for each patient during the RT course. Three experienced physicians outlined on the pCT and rCT all the volumes of interest (VOIs). We used three software solutions (VelocityAI 2.6.2 (V), MIM 5.1.1 (M) by MIMVista and ABAS 2.0 (A) by CMS-Elekta) to generate the automatic contouring on the repeated CT. All the VOIs obtained with automatic contouring (AC) were successively corrected manually. We recorded the time needed for: 1) ex novo ROIs definition on rCT; 2) generation of AC by the three software solutions; 3) manual correction of AC.To compare the quality of the volumes obtained automatically by the software and manually corrected with those drawn from scratch on rCT, we used the following indexes: overlap coefficient (DICE), sensitivity, inclusiveness index, difference in volume, and displacement differences on three axes (x, y, z) from the isocenter. RESULTS: The time saved by the three software solutions for all the sites, compared to the manual contouring from scratch, is statistically significant and similar for all the three software solutions. The time saved for each site are as follows: about an hour for Head&Neck, about 40 minutes for prostate, and about 20 minutes for mesothelioma. The best DICE similarity coefficient index was obtained with the manual correction for: A (contours for prostate), A and M (contours for H&N), and M (contours for mesothelioma). CONCLUSIONS: From a clinical point of view, the automated contouring workflow was shown to be significantly shorter than the manual contouring process, even though manual correction of the VOIs is always needed.

Sinonasal malignancies and charged particle radiation treatment: a systematic literature review.

Background. Paranasal and nasal cavity malignancies are rare tumors that frequently present at advanced stages. Tumor extension and anatomic complexity pose a challenge for their treatment. Due to their peculiar physical and biological properties particle radiation therapy, i.e. protons and ions can have a role in their management. We performed a systematic literature review to gather clinical evidence about their use to treat sinonasal malignancies. Materials and Methods. We searched the browsers PubMed and Medline as well as specific journals and conference proceedings. Inclusion criteria were: at least 10 patients, English language, reporting outcome and/or toxicity data. Results. We found six studies with data on clinical outcome. Carbon and helium ions were each used in one study, protons in four. Toxicity was specifically described in five studies. One reported acute toxicity of carbon ions, one dealt with brain toxicity from both carbon ions and protons. Three papers reported on visual toxicity: one from carbon ions, one from protons and one from both. Specific data were extracted and compared with the most pertinent literature. Conclusion. Particle radiation therapy is in its early phase of development. Promising results achieved so far must be confirmed in further studies.

Risk of sinonasal-cutaneous fistula after treatment for advanced sinonasal cancer.

BACKGROUND AND OBJECTIVES: To determine the rate and the risk factors for sinonasal-cutaneous fistula formation after treatment for sinonasal malignancy. METHODS: Between 1991 and 2002, 99 patients with advanced sinonasal malignancy received radiation therapy +/- surgery. Primary site was maxillary sinus in 30, ethmoid sinus in 19, nasal cavity in 32, nasopharynx in 3, and sphenoid sinus in 15 patients. Eighty-two percent of patients had T4 disease. Sixty-eight percent of patients had undergone surgical resection. Median follow-up was 70.6 months. RESULTS: Eight patients developed ≥ grade 3 sinonasal-cutaneous fistulas at a median time of 3.8 months after radiation. The overall rates of developing ≥ grade 3 fistulas in the entire group at 2 and 5 years were 6% and 10%, respectively. The fistulas were in the medial canthus in seven patients and in the infraorbital region in one patient. Fistulas developed exclusively along the transfacial incision scar and in patients whose tumors extended to the subcutaneous tissues. In univariate analysis, squamous cell carcinoma histology (P » 0.008), ≤ T4a primary tumor category (P » 0.02), and transfacial incision (P » 0.02) were associated with increased risk of fistula formation. CONCLUSIONS: Histologic subtype, T category, and quality of the skin and the underlying supporting tissues after transfacial incision are risk factors for sinonasal-cutaneous fistula formation.

Effect of radiotherapy and chemotherapy on the risk of mucositis during intensity-modulated radiation therapy for oropharyngeal cancer.

PURPOSE: To define the roles of radiotherapy and chemotherapy on the risk of Grade 3+ mucositis during intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer. METHODS AND MATERIALS: 164 consecutive patients treated with IMRT at two institutions in nonoverlapping treatment eras were selected. All patients were treated with a dose painting approach, three dose levels, and comprehensive bilateral neck treatment under the supervision of the same radiation oncologist. Ninety-three patients received concomitant chemotherapy (cCHT) and 14 received induction chemotherapy (iCHT). Individual information of the dose received by the oral mucosa (OM) was extracted as absolute cumulative dose-volume histogram (DVH), corrected for the elapsed treatment days and reported as weekly (w) DVH. Patients were seen weekly during treatment, and peak acute toxicity equal to or greater than confluent mucositis at any point during the course of IMRT was considered the endpoint. RESULTS: Overall, 129 patients (78.7%) reached the endpoint. The regions that best discriminated between patients with/without Grade 3+ mucositis were found at 10.1 Gy/w (V10.1) and 21 cc (D21), along the x-axis and y-axis of the OM-wDVH, respectively. On multivariate analysis, D21 (odds ratio [OR] = 1.016, 95% confidence interval [CI], 1.009-1.023, p < 0.001) and cCHT (OR = 4.118, 95% CI, 1.659-10.217, p = 0.002) were the only independent predictors. However, V10.1 and D21 were highly correlated (rho = 0.954, p < 0.001) and mutually interchangeable. cCHT would correspond to 88.4 cGy/w to at least 21 cc of OM. CONCLUSIONS: Radiotherapy and chemotherapy act independently in determining acute mucosal toxicity; cCHT increases the risk of mucosal Grade 3 toxicity ≈4 times over radiation therapy alone, and it is equivalent to an extra ≈6.2 Gy to 21 cc of OM over a 7-week course.

Pharyngoesophageal stricture after treatment for head and neck cancer.

BACKGROUND: The purpose of this study was to report the risk of pharyngoesophageal stricture after treatment for head and neck cancer. METHODS: Human studies on radiation therapy with or without chemotherapy for head and neck cancer published in peer-reviewed journals with assessment of pharyngoesophageal stricture with barium swallow or endoscopy were included. RESULTS: A total of 4727 patients from 26 studies treated between 1989 and 2008 were eligible for analysis. The reported overall risk of stricture was 7.2%. The risks of pharyngoesophageal stricture in both conventional and intensity-modulated radiation therapy (IMRT) studies were 5.7% and 16.7%, respectively (p < .001). Use of concurrent (p < .001) and taxane (p = .01) chemotherapy was associated with the IMRT technique. Prospective studies reported a 3.3-fold increased risk of stricture compared with that of retrospective studies (odds ratio: 3.3; 95% confidence interval: 2.3-4.8; p < .001). CONCLUSIONS: Pharyngoesophageal stricture after IMRT and chemotherapy treatment for head and neck cancer is not uncommon. Videofluoroscopic swallow study should be performed prospectively to evaluate swallowing function.

A systematic review of proton therapy in the treatment of chondrosarcoma of the skull base.

Chondrosarcoma (CSA) of the skull base (SB) is an uncommon, slowly growing, neoplasm comprising approximately 0.1% of all intracranial tumors and 6% of SB lesions. Even though its growth is slow, CSA is a potentially lethal tumor. The therapeutic approach to CSA of the SB is still controversial and clinical experience is limited because of the relative rarity of this tumor. The use of proton therapy (PT) after maximal surgery is widely accepted, but there are no controlled studies demonstrating the need of PT and its superiority in comparison to radiotherapy with photons. We conducted a systematic review of the scientific literature published during the period between January 1980 and June 2008 on data regarding irradiation of CSA of the SB with PT and a series of inclusion criteria. During August 2008, two independent reviewers (M.A. and D.A.), by applying the key words "skull base", "chondrosarcoma", and "proton therapy" selected those studies from the PubMed database in which a minimum of ten patients received palliative, radical, or postoperative irradiation with protons and which furnished a minimum of 24 months of follow-up. Forty nine reports were retrieved. There were no prospective trials (randomized or nonrandomized) but just nine uncontrolled single-arm studies for PT mainly related to advanced and frequently incompletely resected tumors. According to the inclusion criteria, only four articles, reporting the most recent updated results of the publishing institution, were included in the analysis providing clinical outcomes for 254 patients in total. Therapeutic approach to CSA of the SB has traditionally relied on surgical control. Radiation therapy has demonstrated to be a valuable modality for local control in the postoperative setting or in advanced/inoperable cases treated with definitive intent. The use of PT following maximal surgical resection shows a very high probability of medium- and long-term cure with a relatively low risk of significant complications.

Diagnostic evaluation of squamous cell carcinoma metastatic to cervical lymph nodes from an unknown head and neck primary site.

OBJECTIVES/HYPOTHESIS: To discuss our experience with the diagnostic evaluation in patients with squamous cell carcinomas (SCCAs) of the head and neck metastatic to the cervical lymph nodes from an unknown primary site. METHODS: Between June 1983 and December 2008, 236 patients were evaluated with lymph node biopsy, computed tomography (CT), and/or magnetic resonance imaging (MRI) of the head and neck, and panendoscopy with directed biopsies. Additional studies included fluorodeoxyglucose-single photon emission computed tomography (FDG-SPECT) in 26 patients and FDG-positron emission tomography (FDG-PET) or FDG-PET/CT in 21 patients. Seventy-nine patients underwent an ipsilateral (72) or bilateral (seven) tonsillectomy. RESULTS: An occult primary site was detected in 126 patients (53.4%); six patients had two synchronous primary cancers. The most common primary sites were in the tonsillar fossa (59 patients; 44.7%) and the base of tongue (58 patients; 43.9%). The primary site was found in 21 (29.2%) of the 72 patients with no suspicious findings on physical exam and/or radiographic evaluation compared with 105 (64.0%) of 164 remaining patients. Tonsillectomy revealed the primary cancer in 35 (44.3%) of 79 patients. FDG-SPECT and FDG-PET or FDG-PET/CT was the sole method of primary site detection in only one patient (2.1%) of 47 patients. CONCLUSIONS: Diagnostic evaluation should include a thorough physical examination, CT and/or MRI of the head and neck, and panendoscopy with directed biopsies. Unilateral or bilateral tonsillectomy should be performed on patients with adequate lymphoid tonsillar tissue. FDG-PET or FDG-PET/CT should be considered for those with indeterminate findings on physical examination and/or head and neck CT and/or MRI if those sites are located outside of the oropharynx.