BACKGROUND:Historically, survival for even highly select cohorts of brain metastasis patients selected for SRS alone is <2 yr; thus, limited literature on risks of recurrence exists beyond 2 yr. OBJECTIVE:To investigate the possibility that for subsets of patients the risk of intracranial failure beyond 2 yr is less than the commonly quoted 50% to 60%, wherein less frequent screening may be appropriate. METHODS:As a part of our institutional radiosurgery database, we identified 132 patients treated initially with stereotactic radiosurgery (SRS) alone (± pre-SRS surgical resection) with at least 2 yr of survival and follow-up from SRS. Primary study endpoints were rates of actuarial intracranial progression beyond 2 yr, calculated using the Kaplan-Meier and Cox regression methods. RESULTS:The median follow-up from the first course of SRS was 3.5 yr. Significant predictors of intracranial failure beyond 2 yr included intracranial failure before 2 yr (52% vs 25%, P < .01) and total SRS tumor volume ≥5 cc (51% vs 25%, P < .01). On parsimonious multivariate analysis, failure before 2 yr (HR = 2.2, 95% CI: 1.2-4.3, P = .01) and total SRS tumor volume ≥5 cc (HR = 2.3, 95% CI: 1.2-4.3, P = .01) remained significant predictors of intracranial relapse beyond 2 yr. CONCLUSION:Relapse rates beyond 2 yr following SRS alone for brain metastases are low in patients who do not suffer intracranial relapse within the first 2 yr and with low-volume brain metastases, supporting a practice of less frequent screening beyond 2 yr. For remaining patients, frequent (every 3-4 mo) screening remains prudent, as the risk of intracranial failure after 2 yr remains high.

BACKGROUND:Postoperative stereotactic radiosurgery for brain metastases potentially offers similar local control rates and fewer long-term neurocognitive sequelae compared to whole brain radiation therapy, although patients remain at risk for distant brain failure (DBF). OBJECTIVE:To describe clinical outcomes of adjuvant stereotactic radiosurgery for large brain metastases and identify predictors of intracranial failure and their implications on optimal patient selection criteria. METHODS:We performed a retrospective review on 100 large (>3 cm) brain metastases in 99 patients managed by resection followed by postoperative stereotactic radiosurgery to a median dose of 22 Gy (range, 10-28) in 1 to 5 fractions (median, 3). Primary histology was nonsmall cell lung in 40%, breast cancer in 18%, and melanoma in 17%. Forty (40%) patients had uncontrolled systemic disease. RESULTS:With a median follow-up of 12.2 months (range, 0.6-87.4), the 1-year Kaplan-Meier local control was 72%, DBF 64%, and overall survival 55%. Nine patients (9%) developed evidence of radiation injury, and 6 (6%) developed leptomeningeal disease. Uncontrolled systemic disease (P=.03), melanoma histology (P=.04), and increasing number of brain metastases (P<.001) were significant predictors of DBF on Cox multivariate analysis. Patients with <4 metastases, controlled systemic disease, and nonmelanoma primary (n=47) had a 1-year DBF of 48.6% vs 80.1% for all others (P=.01). CONCLUSION:Postoperative stereotactic radiosurgery to the resection cavity safely and effectively augments local control of large brain metastases. Patients with <4 metastases and controlled systemic disease have significantly lower rates of DBF and are ideal treatment candidates.

In the elderly population, treatment of pancreatic adenocarcinoma is often complicated by significant comorbidities that preclude surgery, chemotherapy and/or conventional external beam radiation therapy (EBRT). In this population, stereotactic body radiation therapy (SBRT) has gained great interest as a promising modality in patients with adenocarcinoma of the pancreas. A retrospective review of 36 patients of age ≥ 80 with adenocarcinoma of the pancreas treated with definitive or adjuvant SBRT ± chemotherapy between January 2007 and May 2011 was performed. Twenty-six patients (72%) were treated definitively with SBRT, 4 patients (11%) received adjuvant SBRT with close or positive margins, and 6 (17%) patients received SBRT for recurrent disease. 19% of the patients had stage I disease, 39% were stage II, 19% were stage III, 6% were stage IV, and 17% were recurrent disease. Three patients (8%) received neoadjuvant chemotherapy, and 7 patients (19%) received it adjuvant setting. The median dose was 24Gy (24-36 Gy) given in 1-3 fractions. Kaplan-Meier was used to estimate overall survival (OS), local control (LC), and freedom from metastatic disease (FFMD). Cox regression was used to identify significant predictors of those outcomes. The median age of patients was 85 (range 80-91) with a median follow-up of 10 months (range 2.3-28.5). Seventy-five percent of patients (27/36) had follow-up imaging. The median planning target volume was 17.3cc (6.1-59.2cc). The median OS was 8.4 months, 6-month actuarial OS was 61% and 12-month actuarial OS was 28.9%. Median LC was 13.2 months, 6-month LC was 60% and 12-month actuarial LC was 54%. There were no independent predictors for LC. FFMD was 8.4 months, and 12-month actuarial rate was 49%. Fourteen patients (39%) had local failures, 12 (33%) had distant metastasis, and 7 (19%) had both. The most common site of distant metastasis was the liver (50%). Only one patient was unable to complete treatment due to pain, and there were no acute or late ≥ grade 3 toxicities. SBRT is feasible, safe and effective in an elderly population with co-morbid conditions which frequently make them ineligible for surgical management. For patients who are medically operable but have high-risk features post resection, SBRT can reduce the risk of local failure without the penalty of increased toxicity. SBRT appears to be a promising alternative to definitive EBRT with a more convenient treatment regimen, shorter overall treatment time and appears to be better tolerated. A prospective trial is currently underway to assess the efficacy of this approach.

Stereotactic body radiation therapy (SBRT) has seen increasing use as a salvage strategy for patients with recurrent, previously-irradiated squamous cell carcinoma of the head and neck (rSCCHN). It is unknown which PET characteristics correlate best with tumor control. We investigated whether PET SUV metrics on initial post-treatment PET-CT scan could predict subsequent local failure (LF) in patients with initial response or stable disease after SBRT for rSCCHN. A retrospective cohort study of 37 patients with rSCCHN treated with SBRT between 2005 and 2009. Patients were included if they had a pre-treatment PET-CT scan, at least two post-treatment PET-CT scans, and demonstrated either initial complete response (CR), partial response (PR), or stable disease (SD) with no LF on first follow-up PET-CT. Treatment planning scans with planning target volumes (PTVs) were deformably registered to pre and post-treatment PET-CTs using VelocityAI. SUVmax and SUVmean within the PTV was recorded for each PET-CT. Local failures were contoured on the second or later post-treatment PET-CT and defined as any failure whose nearest edge was within 1 cm of the PTV. SUVmax and SUVmean within PTV were compared to development of LF. Median time from completion of SBRT to first post-treatment PET-CT was 2 months (range 1.1-5.3 mo). Eighteen of 37 patients (49%) developed LF. Estimated median LF-free survival was 12.2 months. Higher SUVmax on initial post-treatment PET-CT was associated with significantly shorter time to LF both as a continuous variable (Cox regression p=0.01) and with a cut point of SUVmax > 4.0 (log rank p=0.011). 13/18 patients (72%) with SUVmax > 4.0 on initial post-treatment PET-CT developed subsequent LF vs. 5/19 patients (26%) with SUVmax < 4.0 (chi-square p=0.009). Higher pre-treatment SUVmean was associated with a borderline significant shorter time to LF (p=0.056). There was no significant association between time to LF and pre-treatment SUVmax (p=0.1) or initial post-treatment SUVmean (p=0.23). Analysis of PET SUV metrics may provide valuable early clues to long-term prognosis in patients with rSCCHN treated with SBRT. SUVmax within PTV on first post-treatment PET-CT was found to predict subsequent local failure in patients with initial CR/PR/SD. The threshold SUVmax appeared to be 4.0, above which patients were at a higher risk of LF. These findings may help clinicians predict whether patients who initially respond or have stable disease will eventually fail SBRT.

The spine is the 3rd most common site of involvement with metastatic disease and nearly 2/3 of patients with systemic disease will have tumors involving the spine resulting in significant neurologic, functional and QOL impairment. Though external beam radiation therapy (RT) and surgical stabilization are the mainstay of management, few options remain for patients with prior treatment. We sought to compare the clinical outcomes, efficacy & toxicity of SRS in the management of metastatic tumors to the spine using single (SS) or multi-session fraction (3–5 fraction MS) session at 2 large academic centers. A retrospective review was conducted of MS (GUMC, 104 patients with 149 lesions) and SS (UPCI, 126 patients with 197 lesions) treated from 2000–2009 with CyberKnife robotic radiosurgery (Accuray, Inc, Sunnyvale, CA). Outcomes were assessed based on histology, area of involvement, neurological symptoms, pain, response to treatment & need for re-treatment. There were 52.8% female in the MS & 52.5% in the SS group. The thoracic or lumbar spine was treated in 70.9% of the MS & 77% of SS group. The median prescribed dose was 21 Gy (range, 7.5–35) in the MS group and 16 Gy (range, 6–20) in the SS group. Statistical analysis was performed with chi-square test for the categorical variables & t test for continuous variables. An alpha = 0.05 significance level was chosen; the null hypothesis was rejected if the p value was < alpha. Median follow-up for the entire cohort was 253 days (290 d for MS and 234 d for SS) The use of RT prior to SRS was similar in both groups (56% for MS ; 53% for SS). Prior RT dose differed between the groups: 73% of MS patients received 30–40 Gy vs. 93% of the SS having received 20 Gy. 1-year OS was 61% for the MS & 46% for the SS group. Of the patients treated in the MS group, 97% were treated for pain compared to 99% of patients in the SS arm. In the MS group, pain improvement was reported in 74%, stabilization of pain in 22% of patients compared to 75% & 25%, respectively in the SS group. 35% of patients in the MS arm presented with neurological symptoms of whom 36% improved compared to 6% in the SS arm of whom 38% of patients improved. These responses were durable at 4 months. Adverse events after SRS were observed in 7% of MS patients (Grade 1 events) & 54% of SS patients (including 2 Grade 2 events); this difference was statistically significant (p < 0.0001). SRS for spinal metastases is safe & provides durable improvement in neurological function. Furthermore, SRS appears effective in relieving pain in excess of 75% of patients either as a single or multi-fraction approach. Further modeling of duration of pain relief & need for retreatment will be presented. Preliminary review of the data suggests that multi-session SRS is associated with a lower morbidity than SS irradiation.

Pancreatic cancer is the 4th leading cause of cancer death in the United States. The median survival of resected and unresected patients (pts) is approximately 16-20 months and 6-10 months, respectively. Local failure remains a critical problem and the role of radiation therapy remains controversial. SBRT with its precise targeting capabilities, more conformal dose distribution, and short treatment time has several theoretical advantages over conventional external beam radiation therapy. The aim of this study was to assess safety, local control, and time-to-local progression (TTLP) with SBRT in pts with resected and unresected pancreatic cancer. We reviewed our experience with 71 consecutively treated pts (37 M, 34 F, mean age 70.2 ± 12.8 years) treated with SBRT for pancreatic cancer between July 2004-January 2009. Forty pts (56%) had unresectable disease, 11 pts (16%) had recurrent disease, 8 pts (11%) had palliative SBRT, and 12 pts (17%) received adjuvant SBRT for close or positive margins. The median dose was 24 Gy (range 18 - 25 Gy) in 1 - 3 fractions. Sixty-nine pts were treated with the Cyberknife® robotic radiosurgery system [Accuray, Sunnyvale, CA] and 2 pts were treated with Trilogy™ Intensity-modulated radiosurgery (IMRS) [Varian Medical Systems Inc., Palo Alto, CA]. Kaplan-Meyer survival analyses were used to estimate local control (LC) and overall survival (OS) rates. The median follow-up for all pts was 6 months (0.3 - 26 mo), and among surviving pts it was 11 months (4 - 26 mo). The median tumor volume was 17 cc (5.1 - 249cc). The overall LC rate for all pts was 64.8%, and 68.4% & 60.7% for resected and unresected disease, respectively. The LC rates at 6 months/1 year were 71.7%/48.5%. The median TTLP was 3.6 months, and 3.3, 10.9, 3.2, and 3.1 months for palliative, adjuvant, recurrent and unresectable disease. The LC rate for tumor size<15cc (n = 31) was 74.2%, and 57.5% for>15cc (n = 40) (p = 0.02). The median OS was 10.3 months, with 6 month/1 year OS rates of 65.3%/41%. The 6 month/1 year OS for adjuvant, palliative, recurrent and unresectable were 100%/81.8%, 25%/0%, 77.9%/58.4%, and 58.8%/32.6%. Grade 1-2 acute and late GI toxicity were seen in 10-13% of pts. No pts experienced grade 3 or 4 toxicity, including bowel perforation, secondary to SBRT. SBRT using Cyberknife®-SRS and Trilogy™-IMRS is feasible with minimal toxicity. Larger tumor size is associated with significantly lower LC. The overall local control rate for all pts was 64.8%, comparable to rates with EBRT. This shorter treatment course can be delivered without delay in adjuvant chemotherapy. Further studies are needed to better assess SRS for pancreatic CA.

Results: Nearly half the pts filled out a survey before IMRT (48%) with an average follow-up of 16.5 months (1.4‐50.6). Tumor primarysiteincludedhypopharynx(n=10),larynx(n=38),oral cavity(n= 21),oropharynx(n=50), salivarygland(n=10),sinus (n = 6), and thyroid (n = 8). The majority of patients were advanced as follows: stage I (n = 8), stage II (n = 25), stage III (n = 38), stage IV (n = 61), with five patients treated for recurrence and unknown stage in six patients. Ninety-seven (68%) patients received concurrent chemotherapy and 20 patients were treated with surgery followed by post-op RT alone. Mean dose to the right and left parotid averaged 28 and 27 Gy, respectively, with higher radiation dose to the parotid significantly lowering patients’ score in the domains of saliva, chewing, taste, swallowing and pain. Conclusions: Our data suggests that there is acute decrement in QOL in all domains except pain and anxiety, which appear to improve over the first 3 months. Most domains return to baseline between 9 and 12 months from initiating treatment, except taste and saliva, which continued to show slow recovery over an extended period of time (up to 3 years). The overall QOL appears to suggest near recovery nine months from beginning treatment in the vast majority of patients.

Background/Aims: Large clinical experience with spinal radiosurgery to properly assess clinical experience has previously been limited. This study evaluated the clinical outcomes of single fraction radiosurgery as part of the management of metastatic spine tumors. Methods: Five hundred patients with spinal metastases underwent radiosurgery (ages ranged from 18 to 85 years, mean 56 years). Lesion location included 73 cervical, 212 thoracic, 112 lumbar, and 103 sacral. The most common metastatic tumors were renal cell (93 cases), breast (83 cases), and lung (80 cases). Results: The primary indication for radiosurgery was pain in 336 cases, as a primary treatment modality in 65 cases, for radiographic tumor progression in 51 cases, for post-surgical treatment in 9 cases, for progressive neurological deficit in 32 cases, and as a radiation boost in 7 cases. The maximum intratumoral dose ranged from 12.5 to 25 Gy (mean 20 Gy). Tumor volume ranged from 0.20 to 264 ml (mean 46 ml). Axial and/or radicular pain improved in 290 of 336 patients (86%). Long-term tumor control was demonstrated in 90% of lesions treated with radiosurgery as a primary treatment modality and in 88% of lesions treated for radiographic tumor progression. Twenty-seven of 32 patients (84%) with a progressive neurological deficit prior to treatment experienced at least some clinical improvement. Conclusions: Spinal stereotactic radiosurgery is demonstrated to be a feasible, safe, and clinically effective technique for the treatment of spine metastases. Copyright (c) 2006 S. Karger AG, Basel.

Purpose/Objective: To evaluate the incidence of acute skin toxicity in patients with breast cancer treated with intensity modulated radiation therapy (IMRT) following breast conserving surgery.Materials/Methods: Between February 2003 and January 2005, 506 patients with early stage breast cancer underwent breast conservation surgery and definitive breast irradiation using 2-angle tangential field IMRT. The median dose delivered to the entire breast was 50 Gy in 25 fractions. Electron beam boost to the lumpectomy cavity was delivered via enface electrons with a median dose of 10 Gy for a median total dose of 60 Gy in 30 fractions. Throughout the course of radiation treatment, all patients were evaluated on a weekly basis by the treating radiation oncologist for acute skin toxicity including erythema and desquamation which were graded using the RTOG toxicity scale.Results: The median breast volume (TV) in this cohort of patients was 894 cc (range 104–3387 cc). For all patients, the incidence of acute erythema grades 0,1,2, and 3 were 23%, 45%, 31%, and 1%, respectively. The rates of acute skin desquamation grades 0,1,2, and 3 were 81.5%, 14%, 4%, and 0.5%, respectively. The median maximum dose delivered to the TV was 55 Gy using IMRT. The median % of TV receiving more than the prescribed dose was 83%. The median % of TV receiving more than 110% and less than 95% of prescribed dose was 0% and 8%, respectively. The incidence of desquamation significantly correlated with TV (p<0.001), max dose to TV (p=0.017) and % TV receiving more than prescribed dose (p=0.016). There was no significant correlation of these dosimetric quantities or TV to skin erythematic grade.Tabled 1Correlation Analysis of Breast Volume and Dosimetric Values with Acute Skin Desquamation Toxicity for Breast IMRT Purpose/Objective: To evaluate the incidence of acute skin toxicity in patients with breast cancer treated with intensity modulated radiation therapy (IMRT) following breast conserving surgery. Materials/Methods: Between February 2003 and January 2005, 506 patients with early stage breast cancer underwent breast conservation surgery and definitive breast irradiation using 2-angle tangential field IMRT. The median dose delivered to the entire breast was 50 Gy in 25 fractions. Electron beam boost to the lumpectomy cavity was delivered via enface electrons with a median dose of 10 Gy for a median total dose of 60 Gy in 30 fractions. Throughout the course of radiation treatment, all patients were evaluated on a weekly basis by the treating radiation oncologist for acute skin toxicity including erythema and desquamation which were graded using the RTOG toxicity scale. Results: The median breast volume (TV) in this cohort of patients was 894 cc (range 104–3387 cc). For all patients, the incidence of acute erythema grades 0,1,2, and 3 were 23%, 45%, 31%, and 1%, respectively. The rates of acute skin desquamation grades 0,1,2, and 3 were 81.5%, 14%, 4%, and 0.5%, respectively. The median maximum dose delivered to the TV was 55 Gy using IMRT. The median % of TV receiving more than the prescribed dose was 83%. The median % of TV receiving more than 110% and less than 95% of prescribed dose was 0% and 8%, respectively. The incidence of desquamation significantly correlated with TV (p<0.001), max dose to TV (p=0.017) and % TV receiving more than prescribed dose (p=0.016). There was no significant correlation of these dosimetric quantities or TV to skin erythematic grade.

Purpose/Objective: Limited data exists for dose-volume relationship of parotid gland when patients receive chemoradiation. The purpose of this study is to evaluate the relationship between parotid dose and severity of acute and "early" late xerostomia for patients receiving chemoradiation for head and neck cancers. Materials/Methods: 333 patients with head and neck cancer (HNC) were treated with intensity modulated radiation therapy (IMRT). Of these, 209 patients (63%) were treated with concurrent chemotherapy & radiation and 124 (37%) were treated with radiation alone. All patients underwent a simulation procedure simulated for IMRT treatment planning in a Uni-frame® head immobilization system (MED-TEC Corp, Orange City, IA) and centrally planned on Varian Eclipse (version 6.5) in a distributed cancer network. The superficial lobe of the parotid gland was contoured and the dose volume histogram for parotid tissue was evaluated using the Eclipse planning system. The mean dose to the parotid gland were obtained. Patients were evaluated during treatment for acute xerostomia using the RTOG toxicity scoring system as well as in follow up after completion of treatment for evaluation of late xerostomia. The maximum scores for the early and late toxicities were used for this study. Patients were divided into two groups: group 1 with patients with mean parotid dose less than 26 Gy and group 2 with patients with mean parotid dose greater than 26 Gy. A non-parametric correlation and Chi square analysis was performed to determine the relationship between these two groups with the grade of acute and late xerostomia for patients treated using IMRT with and without chemotherapy. The median follow up after completion of radiation treatment is 8 months. Results: The median mean parotid dose for HNC patients treated with IMRT with and without chemotherapy is 26.5 and 25 Gy, respectively (p=NS). For all patients with mean parotid dose less than 26 Gy, rate of Grade 2 and 3 acute salivary toxicity were 20% and 3% compared to 33% and 9%, respectively, for patients with mean parotid dose greater than 26 Gy (p=0.005). The rates of Grade 2 and 3 late salivary toxicity for all patients with mean parotid dose < 26 Gy was 8 and 0%, respectively, compared to 23% and 5% for patients with mean parotid dose > 26 Gy (p <0.0001). The grade 2 and 3 acute salivary for toxicities for patients receiving IMRT alone was 16 and 3%, respectively, while 27 and 6%, respectively for patients receiving IMRT and chemotherapy (p<0.0001). For patients with mean parotid dose < 26 Gy, the grade 3 acute and late salivary toxicity was 0 and 0% for patients who were treated with IMRT alone in contrast to 9% and 0%,respectively for patients receiving IMRT and chemotherapy(p=0.001). For patients with mean parotid dose greater than 26 Gy, the Grade 3 acute and late salivary toxicity was 3 and 6%,respectively, for patients treated with IMRT alone compared to 32% and 4%, respectively, for patients receiving chemotherapy and IMRT (p=0.02). Conclusions: This study suggests that distinct dose volume relationships exists for patients treated with chemoradiation versus radiation alone using IMRT for HNC. Patients who received IMRT and chemotherapy had significantly increased acute and late salivary toxicity regardless of the mean parotid dose. A more detailed characterization of this relationship and evaluation of the NTCP is underway with an expanded cohort of patients in order to establish appropriate parotid dose-volume constraints for patients treated with chemoradiation using IMRT.

Purpose/Objective: Acute mucositis is a common acute toxicity for patients treated with radiation therapy for head and neck cancer (HNC) and is significantly increased when combined with chemotherapy. The purpose of this study is to evaluate the correlation between the dose to the oral cavity and the severity of acute mucositis in HNC patients treated with chemotherapy and IMRT. Materials/Methods: Between April 2002 through September 2004, 70 patients with HNC were treated with IMRT with 5–7 fields using dynamic multileaf collimators. All patients also received combination chemotherapy. Patients underwent a simulation procedure for IMRT treatment planning in a Uni-frame® head immobilization system (MED-TEC Corp, Orange City, IA) and centrally planned on Varian Eclipse (version 6.5) in a distributed cancer network. For each patient, the oral cavity was contoured and the dose volume histogram was evaluated using the Eclipse planning system. The median dose delivered to the primary site was 70 Gy. Throughout radiation treatment, all patients were evaluated on a weekly basis by the radiation oncologist to evaluate acute mucositis using the RTOG toxicity scale. The maximum toxicity score was used for this study. Using SPSS 12.0, a non-parametric correlation analysis was performed between the acute mucositis grade and the percent volume of oral cavity receiving doses higher than 15, 30, 40, 45, 50 Gy (V15,V30,V40,V45,V50). Results: The rates of acute mucositis grades 0, 1, 2, and 3 were 6%, 27%, 51% and 16%, respectively. There was no grade 4 or 5 acute mucositis. The median V15, V30, V40, V45, and V50 were 69%, 61%, 30%, 19% and 10%, respectively. There was a statistically significant correlation between acute mucositis grade (p<0.05) and the V15, 30,40,45 (Table 1) while V50 marginal significance (p=0.06). Conclusions: Dose and volume to the oral cavity significantly correlates to the grade of acute mucositis in patients treated with HNC and chemotherapy. The rates of grade 3–4 of mucositis in this study compares favorably to recent clinical trial data (RTOG 91-11) in patients treated with conventional radiation techniques (43% vs. 16%). Further investigation is warranted to explore the dose volume relationship parameters and normal tissue complication probability (NTCP) for oral cavity. Once found, dose volume constraints could be used for IMRT inverse planning to further reduce the incidence of acute mucositis when chemotherapy is used in conjunction with IMRT. Tabled 1Correlation Analysis of Percent Volume of Oral Cavity Receiving More Than 15,30,40,45,50 Gy with Grade of Acute Oral Mucositis

The dioxygenyl salts O2MF6 or O2M2F11 where M = As, Sb, Bi, Nb, Ta, Ru, Au, and Pt, were hydrolysed aqueous base (40% NaOH) to evaluate their purity and to gain further information about their thermal instability. Compounds containing As, Sb, Bi, Nb and Ta yielded 1.25 moles O2 per mole of starting material whereas for compounds containing Ru, Au and Pt, 1.5 moles of O2 per mole of salt was produced. The difference is a consequence of the greater oxidizing power of the RuF-6, AuF-6 and PtF-6 anions. All of the dioxygenyl salts are intrinsically unstable at room temperature in vacuum.