Search

Background: Patients with HER2-positive breast cancer have a significant risk of developing brain metastases (BrM), which have detrimental effects on survival outcomes and quality of life. Although there are several systemic treatment options available that may delay the appearance of BrM and secondary progression of previously treated BrM, there are still substantial unmet needs for this patient population and primary prevention remains elusive., Methods: A group of experts created consensus statements, through a modified Delphi process, to bridge the gap between current unmet needs, available evidence, and international guidelines., Results: The steering committee reviewed all relevant literature and formed research questions to be answered by the subsequent consensus statements. In total, 61 contributors provided feedback on the consensus statements, with 34 statements reaching agreement out of the 55 statements that were voted on altogether. Statements with consensus aimed to define BrM primary and secondary prevention, screening procedures, assessment of symptoms, treatment efficacy, and preventing the occurrence and progression of BrM, while acknowledging the possibilities and limitations in daily clinical practice. Some statements did not reach agreement for a variety of reasons, mostly due to lack of evidence., Conclusions: The consensus statements outlined in this publication provide a point of reference for daily clinical practice and can act as recommendations for clinical trial procedures and future guidelines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Hypofractionated proton beam radiotherapy (PBT) is gaining attention in early-stage non-small cell lung cancer (ES-NSCLC). However, there is a large unmet need to define indications, prescription doses and potential adverse events of protons in this clinical scenario. Hence, the present work aims to provide a critical literature revision, and to investigate associations between fractionation schedules/ biological effective doses (BEDs), oncological outcomes and toxicities., Materials and Methods: This systematic review and meta-analysis complied with the PRISMA recommendations. Inclusion criteria were: 1) curative-intent hypofractionated PBT for ES-NSCLC (≥3 Gy(RBE)/fraction), 2) report of the clinical outcomes of interest, 3) availability of full-text written in English. The bibliographic search was performed on the NCBI Pubmed, Embase and Scopus in September 2021; no other limitations were applied. The BED was calculated for each included study (α/β = 10 Gy); the median BED for all studies was used as a threshold for stratifying selected evidence into "high" and "low"-dose subgroups. Heterogeneity was tested using chi-square statistics; inconsistency was measured with the I 2 index. Pooled estimate was obtained by fitting both the fixed-effect and the DerSimonian and Laird random-effect model., Results: Eight studies and 401 patients were available for the meta-analysis; median follow-up was 32.8 months. The median delivered BED was 105.6 Gy(RBE). A BED ≥ 105.6 Gy(RBE) consistently provided superior OS, CSS, DFS and LC rates (i.e.: 4-year OS: 0.56 [0.34-0.76] for BED < 105.6 Gy(RBE) and 0.78 [0.64-0.88] for BED ≥ 105.6 Gy(RBE)). The meta-analysis of proportions showed a comparable probability of developing acute grade ≥ 2 toxicity between the two groups, while the probability of any late grade ≥ 2 event was almost three-times greater for BED ≥ 105.6 Gy(RBE), with rib fractures being more common in the high dose group., Conclusion: Hypofractionated PBT is a safe and effective treatment option for ES-NSCLC; the delivery of BED ≥ 105.6 Gy(RBE) with advanced techniques for uncertainty management has been associated with improved oncological outcomes across all considered time points., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background and Purpose: Between 30% and 47% of patients treated with definitive radiotherapy (RT) for prostate cancer are at risk of intraprostatic recurrence during follow-up. Re-irradiation with stereotactic body RT (SBRT) is emerging as a feasible and safe therapeutic option. However, no consensus or guidelines exist on this topic. The purpose of this ESTRO ACROP project is to investigate expert opinion on salvage SBRT for intraprostatic relapse after RT., Materials and Methods: A 40-item questionnaire on salvage SBRT was prepared by an internal committee and reviewed by a panel of leading radiation oncologists plus a urologist expert in prostate cancer. Following the procedure of a Delphi consensus, 3 rounds of questionnaires were sent to selected experts on prostate re-irradiation., Results: Among the 33 contacted experts, 18 (54.5%) agreed to participate. At the end of the final round, participants were able to find consensus on 14 out of 40 questions (35% overall) and major agreement on 13 questions (32.5% overall). Specifically, the consensus was reached regarding some selection criteria (no age limit, ECOG 0-1, satisfactory urinary flow), diagnostic procedures (exclusion of metastatic disease, SBRT target defined on the MRI) and therapeutic approach (no need for concomitant ADT, consideration of the first RT dose, validity of Phoenix criteria for salvage SBRT failure)., Conclusion: While awaiting the results of ongoing studies, our ESTRO ACROP Delphi consensus may serve as a practical guidance for salvage SBRT. Future research should address the existing disagreements on this promising approach., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Most patients with ductal carcinoma in situ of the breast (DCIS) are eligible for breast conservation treatment. The key management decision is whether to add radiotherapy and/or endocrine therapy to minimize the risk of a subsequent recurrence. Recent analyses indicating a lack of benefit in terms of breast cancer-associated mortality have suggested that more conservative approaches, omitting adjuvant therapy or even surgery, may be advisable in selected patients. These mortality observations are directly influenced by widespread use of mammographic screening which has opened a Pandora's box of subclinical DCIS and early invasive lesions. Confusion as to how aggressively such possibly indolent lesions should be treated has led to misunderstandings among patients and medical professionals. While awaiting further prospective evidence from clinical trials, we endorse an active treatment of DCIS as the standard of care. Our rationale is twofold: invasive recurrences are associated with an increase in breast cancer mortality, which is not the only relevant endpoint for DCIS. The benefit of complete surgical excision, adjuvant radiotherapy and endocrine treatment in preventing recurrence and invasive progression has been demonstrated in DCIS. The challenge now is how to identify DCIS patients who will not progress to invasive carcinoma even without complete excision and, at the other extreme, those patients at the highest risk who require mastectomy for local control. The current controversies over whether and which adjuvant therapy should be implemented can at least in part be addressed by developing effective doctor-patient communications that enable mutual understanding about the management of this biologically heterogeneous disease., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The aim of this review is to present the available radiobiological, technical and clinical data about extreme hypofractionation in primary prostate cancer radiotherapy. The interest in this technique is based on the favourable radiobiological characteristics of prostate cancer and supported by advantageous logistic aspects deriving from short overall treatment time. The clinical validity of short-term treatment schedule is proven by a body of non-randomised studies, using both isocentric (LINAC-based) or non-isocentric (CyberKnife ® -based) stereotactic body irradiation techniques. Twenty clinical studies, each enrolling more than 40 patients for a total of 1874 treated patients, were revised in terms of technological setting, toxicity, outcome and quality of life assessment. The implemented strategies for the tracking of the prostate and the sparing of the rectal wall have been investigated with particular attention. The urinary toxicity after prostate stereotactic body irradiation seems slightly more pronounced as compared to rectal adverse events, and this is more evident for late occurring events, but no worse as respect to conventional fractionation schemes. As far as the rate of severe acute toxicity is concerned, in all the available studies the treatment was globally well tolerated. While awaiting long-term data on efficacy and toxicity, the analysed studies suggest that the outcome profile of this approach, alongside the patient convenience and reduced costs, is promising. Forty-eight ongoing clinical trials are also presented as a preview of the expectation from the near future., (Copyright © 2016. Published by Elsevier Ltd.)

Despite their specific functional consequences, radiotherapy-induced thyroid abnormalities remain under-estimated and underreported. These sequelae may include primary or central hypothyroidism, thyroiditis, Graves' disease, euthyroid Graves' ophthalmopathy, benign adenomas, multinodular goitre and radiation-induced thyroid carcinoma. Primary hypothyroidism, the most common radiation-induced thyroid dysfunction, affects 20-30% of patients administered following curative radiotherapy to the neck region, with approximately half of the events occurring within the first 5 years after therapy. The relative risk of radiation-induced cancer (mainly well-differentiated tumours) is 15-53-fold higher than in non-irradiated population. The aetiology of radiation-induced thyroid injury includes vascular damage, parenchymal cell damage and auto-immune reactions. Total radiotherapy dose, irradiated volume of the thyroid gland, and the extent of prior thyroid resection are among the most important factors associated with the risk of hypothyroidism. The contribution of other treatment modalities (chemotherapy, endocrine therapy) as well as patient- and tumour-related factors is less clear. Reduction in radiation dose to the thyroid gland and hypothalamic/pituitary complex should be attempted whenever possible. New radiotherapy techniques, such as stereotactic radiosurgery, three-dimensional conformal irradiation, intensity modulated radiotherapy and proton therapy allow generally better dose distribution with lower dose to the non-target organs. The diagnostic approach to thyroid radiation injury includes baseline thyroid function assays in all patients undergoing thyroid or parasellar irradiation. Recommended follow-up procedures include at least annual evaluation with a history for symptoms of thyroid dysfunction, clinical examination, and measurement of thyroid hormones and thyrotropin. Management of overt hypothyroidism is based on hormone replacement therapy. Thyroid hormone therapy is also recommended in cases of subclinical hypothyroidism. Treatment of other radiation-induced thyroid disorders (thyroiditis, Graves' disease, thyroid cancer) is similar to that employed in spontaneously occurring conditions. Further improvements in radiotherapy techniques and progress in endocrine diagnostics and therapy may allow better prevention and management of radiation-related thyroid injury.

Cervical lymph node metastases of squamous cell carcinoma from occult primary constitute about 2-5% of all patients with carcinoma of unknown primary site (CUP). Metastases in the upper and middle neck are generally attributed to head and neck cancers, whereas the lower neck (supraclavicular area) involvement is often associated with primary malignancies below the clavicles. The diagnostic procedures include physical examination with thorough evaluation of the head and neck mucosa using fiber-optic endoscopy, biopsies from all suspicious sites or blindly from the sites of possible origin of the primary, computer tomography and/or magnetic resonance. A systematic tonsillectomy in the absence of suspicious lesions is often recommended since up to 25% of primary tumors can be detected in this site. The thoracic primary (tracheal, bronchial, lung, esophagus) has to be excluded, especially in the case of lower neck involvement. Positron emission tomography (PET) with fluoro-2-deoxy-D-glucose allows detection of primary tumor in about 25% of cases, but this procedure is still considered investigational. Therapeutic approaches include surgery (lymph node excision or neck dissection), with or without postoperative radiotherapy, radiotherapy alone and radiotherapy followed by surgery. In early stages (N1), neck dissection and radiotherapy seem to have similar efficacy, whereas more advanced cases (N2, N3) necessitate combined approaches. The extent of radiotherapy (irradiation of bilateral neck and mucosa versus ipsilateral neck radiotherapy) remains debatable. A potential benefit from extensive radiotherapy should be weighted against its acute and late morbidity and difficulties in re-irradiation in the case of subsequent primary emergence. The role of other methods, such as chemotherapy and hyperthermia, remains to be determined.

Despite their particular functional consequences, radiotherapy-induced ear injuries remain under-evaluated and under-reported. These reactions may have acute or late character, may affect all structures of the hearing organ, and result in conductive, sensorineural or mixed hearing loss. Up to 40% of patients have acute middle ear side effects during radical irradiation including acoustic structures and about one-third of patients develop late sensorineural hearing loss (SNHL). Total radiotherapy dose and tumour site seem to be among the most important factors associated with the risk of hearing impairment. Thus, reduction in radiation dose to the auditory structures should be attempted whenever possible. New radiotherapy techniques (3-dimensional conformal irradiation, intensity modulated radiotherapy, proton therapy) allow better dose distribution with lower dose to the non-target organs. Treatment of acute and late external otitis is mainly conservative and includes the anti-inflammatory agents (applied topically and systematically). Post-radiation chronic otitis media and the eustachian tube pathology may be managed with tympanic membrane incision with insertion of a tympanostomy tube (grommet), although the benefit of such approach is controversial and some authors advocate a more conservative approach. In these patients the functional deficit can be alleviated by application of bone conduction hearing aids such as, e.g., the bone anchored hearing aid (BAHA). There is no standard therapy for post-irradiation sudden or progressive SNHL yet corticosteroid therapy, rheologic medications, hyperbaric oxygen or carbogen therapy are usually employed (as for idiopathic SNHL), although controversial data on the efficacy of these treatment modalities have been published. In selected cases with bilateral profound hearing loss or total deafness, cochlear implants may prove effective. Further improvements in radiotherapy techniques and progress in otologic diagnostics and therapy may allow better prevention and management of radiation-related acoustic injury.

The mandible is among the bones most frequently affected by irradiation. The most severe post-radiation injury of the mandible is osteoradionecrosis (ORN). Conflicting data have been reported on the incidence of this complication, its aetiology and management. The incidence of mandibular ORN in head and neck cancer patients managed with radical or postoperative irradiation, has varied widely in the literature from 0.4% to 56%. The interpretation of data derived from particular series are difficult due to the different scoring methods and classification systems used for the evaluation of post-radiation bone damage. Although ORN occurs typically in the first three years after radiotherapy, patients probably remain at indefinite risk. The diagnosis of ORN is principally based on the clinical picture of chronically exposed bone. Radiological symptoms include decreased bone density with fractures, cortical destruction and loss of spongiosa trabeculation. Numerous factors that may be associated with the risk of ORN include treatment-related variables (for example, total radiotherapy dose, biologically effective dose, photon energy, brachytherapy dose rate, combination of external beam irradiation and interstitial brachytherapy, field size, fraction size, volume of the mandible irradiated with a high dose), patient-related variables (like deep parodontitis, pre-irradiation bone surgery, bad oral hygiene, alcohol and tobacco abuse, bone inflammation, dental extraction after radiotherapy) and tumour-related factors (tumour size or stage, proximity of the tumour to bone, anatomic tumour site). Primary management of post-radiation bone lesions include conservative modalities such as saline irrigations, antibiotics during infectious episodes, topically applied antiseptics, gentle sequestrectomy and removal of visibly loosened bone elements as well as treatment with hyperbaric oxygen (HBO). Surgery is reserved for persistent ORN and includes radical resection of the lesion(sequestrectomy, hemimandibulectomy etc.) with reconstruction. In recent years the introduction of preventive oral hygiene measures and meticulous dental evaluations before and after irradiation, improvement in radiotherapy techniques and the development of reliable diagnostic and therapeutic procedures have resulted in a decreased incidence of ORN. Nevertheless, given the severe impact of ORN on patient quality of life, research should be continued to further ameliorate this problem., (Copyright 2002 Elsevier Science Ltd. All rights reserved.)

Although endometrial cancer is the most common female malignancy, evidence-based uniform guidelines for postoperative therapy have not been established. The most logical management is adjuvant irradiation tailored to the extent of surgery, the tumour grade, depth of myometrial invasion, degree of lymph node involvement and age of the patient. Currently, the only widely accepted treatment recommendations are no further therapy in low-risk patients who underwent extensive surgical staging, and external beam radiotherapy (EBRT) in high-risk patients. Most authors recommend postoperative application of only one radiotherapy modality: either brachytherapy (BRT) or EBRT, as their routine combination does not clearly improve the outcome but does increase the risk of late complications. A combination of BRT and EBRT should however be considered in patients with stage II disease, for infiltration of the lower uterine segment, vaginal involvement, positive or close surgical margins, capillary space involvement or unfavourable histology. Two recent randomized studies including mostly intermediate-risk patients managed with either extensive surgical staging or total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH&BSO) with or without postoperative EBRT, showed better local control but no survival benefit from adjuvant irradiation. Two ongoing Gynecologic Oncology Group (GOG) studies compare adjuvant chemotherapy with pelvic or abdominal irradiation in patients with high risk of local relapse. The role of adjuvant radiotherapy (EBRT with or without BRT) in high-risk patients as well as the value of lymphadenectomy in patients fit for such surgery is being addressed in a trial co-ordinated by the Medical Research Council. Future studies are warranted to define whether any irradiation should be employed in intermediate-risk patients and which radiotherapy modality should be used in high-risk node-negative patients with stage I tumours (stage Ib grade 3 and all stage Ic). Other issues which should be addressed in future studies include the extent of surgery, the role of systemic therapies, the relevance of novel biologic prognostic factors, salvage therapies after recurrence, cost-benefit analysis and quality of life., (Copyright 2001 Harcourt Publishers Ltd.)