Background and Objective: A recent report indicated that metastases to other body organs commonly develop after stereotactic body radiation treatment for cure in patients with oligometastases (OGM) confined to one organ. This study was undertaken to determine if the presence of metastatic disease in two other visceral organs (TVO) in patients with conventionally treated brain metastases (BRM) was associated with poorer prognosis.Methods: This retrospective clinical investigation included 26 patients treated for palliation of OGM-BRM between May 1996 and February 2020. These individuals were classified according to the presence (13 patients) or absence (13 patients) of metastases in TVO.Results: With an overall mean follow-up of 16 months, 20 patients were deceased, and 6 patients were alive. The median survivals for the OGM-BRM-TVO and non-OGM-BRM-TVO subsets were 4 and 12 months, respectively; the corresponding crude survival rates at 12 months were 0% and 46% (p < 0.01). Subgroup analysis correlating prognosis to the number of BRM (single vs. multiple) and OGM-BRM categories (synchronous vs. metachronous) failed to reveal a survival advantage favoring a certain subgroup.Conclusion: Although the evidence is speculative, we believe that an aggressive disease condition is more likely present in patients with OGM-BRM-TVO. With the notion of an overall poor survival, we suggest a more tailored, less or nonharmful management approach (i.e., palliative therapy or hospice) for this particular patient cohort.

Supplementary Figures 1-2 from Comparison of radiosensitizing effects of the mammalian target of rapamycin inhibitor CCI-779 to cisplatin in experimental models of head and neck squamous cell carcinoma

Jugulotympanic paraganglioma (JTPG), a benign slow-growing neoplasm in the skull base with a tendency to be locally invasive, poses a treatment challenge because of its proximity to nearby neurovascular structures. The authors describe 11 patents with 12 Fisch-classified JTPGs treated with GammaKnife radiosurgery (GKRS) during a 12-year period. The observed rates of subjective improvement and tumor control were 80% and 83%, respectively. Among the individuals living longer than 5 years, tumor growth developed at 77 and 180 months after radiosurgery in two patients. Treatment-related toxicity or radiation oncogenesis was not observed. GKRS seems to be a valid treatment option for all Fisch designated skull base glomus tumors. Life-long follow-up of these patients is necessary.

Purpose/Objective(s) Jugulotympanic paragangliomas (JTPGs), recognized as slow-growing tumors, represent a treatment challenge because of their known vascular nature, tendency to be locally invasive, location near many vital structures, and their potential to cause very disabling symptoms. This study aimed to examine the outcomes of patients with Fisch-classified JTPGs treated with conventional radiotherapy including stereotactic radiosurgery. Materials/Methods Twenty-four consecutive patients with head and neck paragangliomas diagnosed between November 2003 and May 2017 were identified from the radiation oncology and radiosurgery databases and lists of patients presented for discussion at the weekly Department of Otolaryngology-Head and Neck Surgery multidisciplinary conference. After excluding individuals with carotid body glomus tumors or missing clinical and radiological follow-up information, 13 patients (with a mean age of 61.8 years; 6 glomus tympanicum and 7 glomus jugulare PGs; 10 women and 3 men;) composed the JTPG study participants. Non-invasive stereotactic radiosurgery or external beam radiotherapy was used to treat JTPGs in 11 patients and 2 patients, respectively. The investigation endpoints included subjective and objective responses to treatment (i.e., exhibited symptoms and signs of disease and the tumor) and observed toxicity. Results With regard to the risk designation of JTPGs, seven (54%) belonged to the Fisch A-B categories and six (46%) to C-D categories. During a median follow-up of 36 months (range 7-204) after-therapy, subjective responses consisted of eight patients (62%) who were symptom-free, and five individuals (38%) who did not improve. At a median radioimaging follow-up of 34 months (range 6-204), eight (62%) treated neoplasms were stable, two (15%) showed continued tumor growth, and three (23%) were smaller following radiation treatment. One participant (8%) experienced transient otalgia and tinnitus after external beam irradiation; no patient developed radiation oncogenesis. Long-term follow-up (from 75 to 204 months) was documented in six people (46%). Characterization and effects of treatment were not significantly different between the compared Fisch categorized groups of JTPGs. Conclusion The observed rates of tumor control (85%) and treatment-related toxicity (8%), and the long-term disease progression-free survival of some patients suggest that contemporary radiotherapy is efficacious and safe when applied for Fisch-classified JTPGs. Jugulotympanic paragangliomas (JTPGs), recognized as slow-growing tumors, represent a treatment challenge because of their known vascular nature, tendency to be locally invasive, location near many vital structures, and their potential to cause very disabling symptoms. This study aimed to examine the outcomes of patients with Fisch-classified JTPGs treated with conventional radiotherapy including stereotactic radiosurgery. Twenty-four consecutive patients with head and neck paragangliomas diagnosed between November 2003 and May 2017 were identified from the radiation oncology and radiosurgery databases and lists of patients presented for discussion at the weekly Department of Otolaryngology-Head and Neck Surgery multidisciplinary conference. After excluding individuals with carotid body glomus tumors or missing clinical and radiological follow-up information, 13 patients (with a mean age of 61.8 years; 6 glomus tympanicum and 7 glomus jugulare PGs; 10 women and 3 men;) composed the JTPG study participants. Non-invasive stereotactic radiosurgery or external beam radiotherapy was used to treat JTPGs in 11 patients and 2 patients, respectively. The investigation endpoints included subjective and objective responses to treatment (i.e., exhibited symptoms and signs of disease and the tumor) and observed toxicity. With regard to the risk designation of JTPGs, seven (54%) belonged to the Fisch A-B categories and six (46%) to C-D categories. During a median follow-up of 36 months (range 7-204) after-therapy, subjective responses consisted of eight patients (62%) who were symptom-free, and five individuals (38%) who did not improve. At a median radioimaging follow-up of 34 months (range 6-204), eight (62%) treated neoplasms were stable, two (15%) showed continued tumor growth, and three (23%) were smaller following radiation treatment. One participant (8%) experienced transient otalgia and tinnitus after external beam irradiation; no patient developed radiation oncogenesis. Long-term follow-up (from 75 to 204 months) was documented in six people (46%). Characterization and effects of treatment were not significantly different between the compared Fisch categorized groups of JTPGs. The observed rates of tumor control (85%) and treatment-related toxicity (8%), and the long-term disease progression-free survival of some patients suggest that contemporary radiotherapy is efficacious and safe when applied for Fisch-classified JTPGs.

Background: Characterization of potential beneficiaries from repeat radiosurgery (RRS) for progressive previously treated brain metastases (PPT-BRM) has not received much attention, perhaps because many patients with BRM die following salvage radiosurgery. These individuals remain at risk for neurological deterioration when BRMs are left untreated. Methods: We attempted to study the advantaged people from our four patients and 531 patients identified in a literature search who were treated with RRS for PPT-BRMs. Results: The 2% incidence rate of PPT-BRM from our institution was lower than rates in previous reports (range, 4–25%). The overall efficacy and minimal morbidty associated with RRS have consistently been demonstrated. Even though RRS for PPT-BRM is believed to be essential in patients with good functional status, descriptions of people who benefitted from RRS are poorly documented. Conclusions: RRS for PPT-BRM, generally efficacious, is associated with a low toxicity profile. It is vital that there is careful patient selection for RRS of PPT-BRM given the overall dismal outlook and the potential serious effect of neglected beneficial treatment as well as the intervention-related radionecrosis on the quality of remaining life. Based on the available evidence, we advocate the continued but cautious use of salvage RRS in these people. More research is needed about the patients gaining benefit from the re-irradiation.

F.L. Ampil: None. A. Sin: None. D. Smith: None. T.A. Richards: None.

AbstractAim:Little is known about how integrated positron emission tomography-computed tomography (IPET-CT), both imaging tools and not methods of treatment, contributes to head and neck cancer patients’ outcomes. We analysed the clinical PET-CT findings and their correlation to the effects of applied contemporary disease management.Methodology:A retrospective analysis of 29 individuals who underwent treatment planning fusion of PET-CT for radiochemotherapy of locally advanced head and neck cancer between 2010 and 2016 was undertaken. Gross tumour volumes were categorised as small (≤36 cm3) or large (>36 cm3), and tumour responses to therapy were classified as complete or incomplete.Results:The overall rates of complete tumour response (CTR), 3-year crude survival and failure (all types included) were 80%, 41% and 55%, respectively. Comparative analysis of tumour volume subsets revealed no significant differences in the rates of CTR (p > 0.80), 3-year survival (p > 0.30) and locoregional recurrence (p > 0.70). CTR was associated with improved prognosis (p > 0.05) and fewer tumour relapses (p < 0.02).Conclusion:Our findings, although not truly conclusive, appear in line with those in the literature. Smaller tumour volumes and CTRs shown on integrated PET-CT are likely to play important roles in the promotion of better prognosis, but further study with larger patient numbers and more data are needed.

Abstract Clinical outcomes were reviewed in 30 patients treated by gamma knife radiosurgery for skull base meningiomas with carotid artery encasement (SKBM‐CAE). The overall clinical improvement rate after treatment was 46%. At a median imaging follow‐up of 49 months, tumor volumes were unchanged, were larger, and were smaller or had resolved in 70%, 23%, and 7% of cases, respectively. The crude survival rate at 10 years was 20% and the complication (new cranial nerve deficit not accompanied by imaging‐shown tumor growth) rate was 10%. SKBM‐CAE is amenable to being effectively and safely controlled with the application of gamma knife radiosurgery.

Current combinations of treatment modalities for locally advanced laryngeal cancer (LALC) are the norms of care. In LALC with pre-epiglottic space invasion (PESI), better cure rates are obtained after definitive surgery than with radiotherapy. However, not all patients can undergo surgical intervention for extensive neoplastic disease. Contemporary regimens of combined non-operative therapy for locally advanced head and neck cancer (HNC) are associated with improved results but fraught with increased toxicity. Herein we present a case of a 63-year-old patient who presented with hoarseness, neck pain, otalgia, a large epiglottic mass with fixation of a vocal cord and a lymphadenopathy-free neck. Treatment of LALCPESI with conventional radiochemotherapy and hypertension (HPN) with an angiotensin-I converting enzyme inhibitor (ACEI) medication resulted in long-term, compete clinical remission unaccompanied by untoward complications. To our knowledge, this represents the first case wherein advanced stage HNC completely resolved following standard, non-operative, combined therapy and the incidental use of ACEI. Given that LALC-PESI has been characterized as a radioresistant neoplasm because of the poor vascularized nature of this particular region in the head and neck, standard radiochemotherapy with the important use of ACEI can be a strategy to overcome the resistance offered to combined therapy by very extensive HNC. Nevertheless, more evidence is needed to corroborate this beneficial find.

Carcinoma ex-pleomorphic adenoma (CEPA), an extremely aggressive malignant tumor, bears a significant potential for locoregional recurrence and distant metastases. Management of the disease usually involves definitive surgery with postoperative radiotherapy administered for identified nodal metastases. Two cases of CEPA with many (>50) cervical lymph node metastases and other histopathological features were managed by trimodality treatment scheme. No evidence of disease occurred during follow-up of at least 2 years. These cases may eventually establish the value of surgery with adjuvant radiochemotherapy in patients with CEPA and supernumerary nodal metastases.

The optimum treatment of brain metastases (BRM) in people with poor performance status remains to be ascertained. We aimed to report our reviewed 10‐year stereotactic radiosurgery experience of poor performance status patients with BRM treated at a single institution. Between June 2000 and December 2009, the study participants included 22 consecutive individuals with severe hemiparesis or cerebellar ataxia and stereotactic radiosurgery‐irradiated BRM. The mean follow‐up period was 26 months. Most of the patients were women, aged <65 years and diagnosed with solitary brain metastasis. Extracranial metastases were present in 45% of the patients. A total of 13 individuals (59%) died within 2 months after therapy, and nine patients (41%) died at a much later period. The overall median survival was 2 months, and the 2‐year and 5‐year crude survival rates were 41% and 14%, respectively. Short survival was not predominant after therapy in this limited experience, and the observed prolonged survival suggests that stereotactic radiosurgery still represents a valuable treatment option for poor performance status individuals with BRM.

Metachronous mediastinal and lung metastases (MMLM), important sources of morbidity and mortality, in people with head and neck cancer (HNC) have received little attention. Between 1980 and 2004, 37 patients with treated HNC and MMLM diagnosed on follow-up imaging (with histological confirmation in 14 cases) were identified. The median interval from diagnosis of HNC to the appearance of MMLM was 14.5 months. The overall median survival was 4 months, and the 1-year crude survival rate (CSR) was 16%. A meaningful difference in the 1-year CSRs between the palliative radiation treated and untreated subjects (39% and 4%, respectively, p < 0.01) was observed. Because associated costs of health care utilization are considerable, and yet survival is limited, optimum management of MMLM-HNC with improvement of prognosis remains a challenge.

Locally advanced head and neck cancer (LAHNC) in patients is generally managed with a combination of treatment modalities to improve patient outcomes. Integrated PET-CT radiotherapy planning (RTP) of LAHNC has gained acceptance because of its improved tumor coverage and reduced exposure of normal tissues to radiation; with the fusion of anatomic (CT) and metabolic (PET) information as a single image, the complementary strengths each modality are utilized. Because of the considerable cost of image integration and sparse information, the goal of this retrospective, observational study was to determine the effects (tumor response, failure patterns and survival) of RTP in the contemporary management of LAHNC.

Background: Expediting the process of diagnosis and treatment should theoretically improve outcome. Delays in beginning therapy can cause anxiety to the patients and physicians who may be concerned about tumor progression before treatment is initiated. Treatment delays can be characterized as patient-generated or logistical medical infrastructure prolongations. Objective: The goal of the present study was to determine the impact of stereotactic radiosurgery (RS) consultation to treatment interval (CTI) and the development of additional brain metastases (BRM) during the interim on outcomes after RS. Methods: Between October 2014 and April 2018, 15 individuals developed more contrast-enhancing BRMs during the CTI. These patients were treated with gamma knife RS (including the six patients who underwent gross resection of metastatic intracranial neoplasm). The median duration of CTI was 19 days (range 5-61 days). A comparison of the ≤19 days CTI (eight patients) to the >19 days CTI (seven patients) was performed to assess the effects of the extent of delay to RS. The total number of BRM for RS was 68. The median target volume was 0.48 cm3, and the median margin dose was 24 Gy. Results: Most (67%) of the subjects exhibited good performance status. The overall crude survival rate at two years was 27%; acute or late toxicity after RS was not observed. Comparison of the CTI groups revealed: i) A longer CTI was not associated with a poorer prognosis; ii) BRM recurrence after RS was less common in this patient subgroup; iii) Quality of life (QOL) was satisfactory even though the CTI was prolonged. Conclusion: Acceptable longevity with minimal morbidity satisfying the QOL consideration was found in this audit of cases about CTI and the occurrence of more BRMs during the interim. Decreasing CTI in patients with BRM remains an important goal of quality improvement. Citation Format: Federico Ampil, Gloria Caldito, Troy Richards. Radiosurgery consultation to treatment interval, additional brain metastases during the interim and outcomes after therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4867.

To the Editor, The authors, like most oncologists, routinely treat patients with brain metastases (BRM), because untreated BRM bears a potential toward neurological deterioration, significant morbidity, and mortality. The goal of the present study was to determine the effects of the occurrence of more BRMs during the stereotactic radiosurgery (SRS) consultation and treatment interval (CTI) on outcomes after irradiation. After receiving institutional review board approval, collection of data from available patient records was undertaken. Between October 2014 and April 2018, 15 individuals with a known diagnosis of cancer and radioimaging-demonstrated BRM were treated with single-session gamma knife radiosurgery (including 6 patients who underwent gross resection of the metastatic neoplasm before SRS of the tumor bed cavity). These patients developed more contrast-enhancing intracranial lesions during the CTI. At the time of SRS consultation, seven patients showed solitary metastatic tumors and eight patients had multiple lesions; the average numbers of new BRM for each cohort were two and three, respectively. With respect to SRS, the overall median target volume was 0.48 cm3 (range 0.1–17.2 cm3), and the median margin dose used was 24 Gy (range 12–24 Gy). Survival was measured from the date of SRS for BRM progression to the date of death or last follow up. The mean age was 59 years (range 48–72 years). The majority of patients were men, who were aged <65 years, and had the lung as the primary source of BRM (11/15; 73%). At the time of SRS, most of the patients (10/15; 67%) showed good performance status. BRM was in the supratentorial location in many cases (55/68; 81%). Extracranial metastatic disease was present in close to half (7/15; 47%) of the patients. Only one study participant did not present with a neurological manifestation of BRM. Symptoms (e.g. headache, altered mental status, seizure episodes, blurred vision) and signs of disease (e.g. speech disturbance, limb paresis, unsteadiness/difficult ambulation) were noted in 14 patients (93%). The median duration of CTI was 19 days (range 5–61 days). To assess the effects associated with the extent of delay to radiosurgery, a comparison of CTI of ≤19 days (8 patients) to a CTI of >19 days (7 patients) was carried out. Table 1 shows three interesting findings: (i) a longer CTI was not associated with a poorer prognosis; (ii) BRM recurrence after SRS was less common in this SRS timing subgroup; and (iii) quality of life was satisfactory, even though the CTI was prolonged. The small numbers precluded a meaningful statistical analysis. During this review, five patients were alive at follow up, which ranged from 1 to 39 months. Survival extended from 1 to 23 months in the 10 deceased patients. The overall crude survival rates at 1 year and 2 years were 47% (7/15) and 27% (4/15), respectively. There were no documented cases of acute and late toxicity after SRS. One patient later underwent craniotomy and resection of suspected recurrent tumor; only necrosis was found on histopathological examination of the resected intracranial lesion. Repeat radiosurgery was carried out for recurrent BRM in five patients (33%). In general, it is usually not possible to start treatment at the time of histopathological diagnosis of BRM, and the minimum time between diagnosis and initiation of therapy will be at least 2 weeks.1 The workflow period of SRS for BRM begins with the consultation, followed by insurance authorization, treatment planning using computed tomography or magnetic resonance imaging, and ends with the start of radiosurgery.2 The reported incidence of additional BRMs detected on the day of SRS has ranged from 24% to 49%.3-5 The findings from the present study suggest the expected effects from the application of SRS might not be compromised, even when the CTI in patients is long and additional BRM develop. We maintain the result could be ascribed to the fact that the additional tumors were small in volume (an observation akin to that of Garcia et al.3) and to possible selection bias. In the present situation, the diverse periods of CTI can be attributed to some particulars, such as most (11/15; 73%) of the studied participants lived far away from the city and more than half (9/15; 60%) of the patients belonged to the underprivileged, disadvantaged population of society. Although there is inconsistency regarding the discovery of additional BRM at the time of SRS and its influence on prognosis,3, 5 multiple BRM have been viewed as associated with a poor prognosis.6 This investigation represents a small patient sample, and given its retrospective design, the findings from this account should be interpreted with caution. Nevertheless, the adverse clinical outcome intuitively associated with the development of more BRM during the CTI or period of RS delay was not realized in most of the studied patients. This brief report serves to emphasize that the practice of SRS for additional BRM should not be abandoned. The authors declare that they have read the article and there are no competing interests.

Abstract Little is known about the effects of non‐operative treatment for unresectable head and neck cancer with carotid artery encasement. While induction chemotherapy followed by concurrent chemoradiotherapy/sequential chemoradiotherapy is usually recommended for this disease entity, conclusive evidence regarding the benefit achieved from such therapeutic intervention remains sparse. The authors describe two cases of head and neck cancer with carotid artery encasement managed by induction chemotherapy followed by concurrent chemoradiotherapy, and review the literature. Despite the complete disappearance of the locally advanced tumor after the sequential chemoradiotherapy, recurrence and progression of tumor subsequently developed. The untoward event was believed to be due to the prolongation of the overall treatment time and the radiotherapy course. It is surmised that the continued use of sequential chemoradiotherapy in the management of head and neck cancer with carotid artery encasement can be justified, provided it is aggressive, timely, and without undue prolongations.