Shoji Yomo, Romain Carron, Jean-Marc Thomassin, Pierre-Hugues Roche and Jean Régis
The aim of this study was to perform an accurate analysis of changes in hearing in patients with vestibular schwannoma (VS) who have undergone Gamma Knife surgery (GKS) and distinguish the impact of radiosurgery from the natural course of hearing deterioration due to the tumor itself.
This study was a retrospective review of prospectively collected patient data. A group of 154 patients with unilateral nonsurgically treated VS was conservatively monitored for more than 6 months and then treated with GKS between July 1997 and September 2005. They were followed up with serial clinical examination, MRI, and audiometry. The annual hearing decrease rate (AHDR) was measured before and after radiosurgery, and the possible prognostic factors for hearing preservation were investigated.
The mean dose prescribed to the tumor margins was 12.1 Gy. The mean radiological follow-up period after GKS was 60 months (range 7–123 months). The tumor control rate was 94.8%, and 8 patients underwent subsequent intervention due to tumor progression. The mean audiological follow-up times before and after GKS were 22 and 52 months, respectively. The mean AHDRs before and after GKS were 5.39 dB/year (95% CI 3.31–7.47 dB/year) and 3.77 dB/year (95% CI 3.13–4.40 dB/year), respectively (p > 0.05). The mean pre- and post-GKS AHDRs in patients who initially had Gardner-Robertson (GR) Class I hearing were −0.57 dB/year (95% CI −2.95 to 1.81 dB/year) and 3.59 dB/year (95% CI 2.52–4.65 dB/year), respectively (p = 0.007). The mean pre- and post-GKS AHDRs in patients who initially had GR Class II hearing were 5.09 dB/year (95% CI 1.36–8.82 dB/year) and 4.98 dB/year (95% CI 3.86–6.10 dB/year), respectively (p > 0.05). A subgroup of 80 patients had both early and late post-intervention AHDR assessment (with early referring to the period from GKS to the assessment closest to the 2-year follow-up point and late referring to the period from that assessment to the most recent one); in these patients, the mean early post-GKS AHDR was 5.86 dB/year (95% CI 4.25–7.50 dB/year) and the mean late post-GKS AHDR was 1.86 dB/year (95% CI 0.77–2.96 dB/year) (p < 0.001). A maximum cochlear dose of less than 4 Gy was found to be the sole prognostic factor for hearing preservation.
The present study demonstrated the absence of an increase in AHDR after radiosurgery as compared with the preoperative AHDR. There was even a trend indicating a reduction in the annual hearing loss after radiosurgery over the long term. To fully elucidate a possible protective effect of radiosurgery, longer-term follow-up with a larger group of patients will be required.
Jean Régis, Constantin Tuleasca, Noémie Resseguier, Romain Carron, Anne Donnet, Jean Gaudart and Marc Levivier
Gamma Knife surgery (GKS) is one of the surgical alternatives for the treatment of drug-resistant trigeminal neuralgia (TN). This study aims to evaluate the safety and efficacy of GKS in a large population of patients with TN with very long-term clinical follow-up.
Between July 1992 and November 2010, 737 patients presenting with TN were treated using GKS. Data were collected prospectively and were further retrospectively evaluated at Timone University Hospital. The frequency and severity of pain, as well as trigeminal nerve function, were evaluated before GKS and regularly thereafter. Radiosurgery using the Gamma Knife (model B, C, 4C, or Perfexion) was performed with the help of both MR and CT targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4–14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70–90 Gy) was prescribed.
The safety and efficacy are reported for 497 patients with medically refractory classical TN who were never previously treated by GKS and had a follow-up of at least 1 year. The median age in this series was 68.3 years (range 28.1–93.2 years). The median follow-up period was 43.8 months (range 12–174.4 months). Overall, 456 patients (91.75%) were initially pain free in a median time of 10 days (range 1–180 days). Their actuarial probabilities of remaining pain free without medication at 3, 5, 7, and 10 years were 71.8%, 64.9%, 59.7%, and 45.3%, respectively. One hundred fifty-seven patients (34.4%) who were initially pain free experienced at least 1 recurrence, with a median delay of onset of 24 months (range 0.6–150.1 months). However, the actuarial rate of maintaining pain relief without further surgery was 67.8% at 10 years. The hypesthesia actuarial rate at 5 years was 20.4% and at 7 years reached 21.1%, but remained stable until 14 years with a median delay of onset of 12 months (range 1–65 months). Very bothersome facial hypesthesia was reported in only 3 patients (0.6%).
Retrogasserian GKS proved to be safe and effective in the long term and in a very large number of patients. Even if the probability of long-lasting effects may be modest compared with microvascular decompression, the rarity of complications prompts discussion of using GKS as the pragmatic surgical first- or second-intention alternative for classical TN. However, a randomized trial, or at least a case-matched control study, would be required to compare with microvascular decompression.
Constantin Tuleasca, Romain Carron, Noémie Resseguier, Anne Donnet, Philippe Roussel, Jean Gaudart, Marc Levivier and Jean Régis
The goal of this study was to establish whether clear patterns of initial pain freedom could be identified when treating patients with classic trigeminal neuralgia (TN) by using Gamma Knife surgery (GKS). The authors compared hypesthesia and pain recurrence rates to see if statistically significant differences could be found.
Between July 1992 and November 2010, 737 patients presenting with TN underwent GKS and prospective evaluation at Timone University Hospital in Marseille, France. In this study the authors analyzed the cases of 497 of these patients, who participated in follow-up longer than 1 year, did not have megadolichobasilar artery– or multiple sclerosis–related TN, and underwent GKS only once; in other words, the focus was on cases of classic TN with a single radiosurgical treatment. Radiosurgery was performed with a Leksell Gamma Knife (model B, C, or Perfexion) using both MR and CT imaging targeting. A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.8 mm (range 4.5–14 mm) anterior to the emergence of the nerve. A median maximum dose of 85 Gy (range 70–90 Gy) was delivered. Using empirical methods and assisted by a chart with clear cut-off periods of pain free distribution, the authors were able to divide patients who experienced freedom from pain into 3 separate groups: patients who became pain free within the first 48 hours post-GKS; those who became pain free between 48 hours and 30 days post-GKS; and those who became pain free more than 30 days after GKS.
The median age in the 497 patients was 68.3 years (range 28.1–93.2 years). The median follow-up period was 43.75 months (range 12–174.41 months). Four hundred fifty-four patients (91.34%) were initially pain free within a median time of 10 days (range 1–459 days) after GKS. One hundred sixty-nine patients (37.2%) became pain free within the first 48 hours (Group PF≤ 48 hours), 194 patients (42.8%) between posttreatment Day 3 and Day 30 (Group PF(>48 hours, ≤ 30 days)), and 91 patients (20%) after 30 days post-GKS (Group PF>30 days). Differences in postoperative hypesthesia were found: in Group PF≤ 48 hours 18 patients (13.7%) developed postoperative hypesthesia, compared with 30 patients (19%) in Group PF(>48 hours, ≤ 30 days) and 22 patients (30.6%) in Group PF>30 days (p = 0.014). One hundred fifty-seven patients (34.4%) who initially became free from pain experienced a recurrence of pain with a median delay of 24 months (range 0.62–150.06 months). There were no statistically significant differences between the patient groups with respect to pain recurrence: 66 patients (39%) in Group PF≤ 48 hours experienced pain recurrence, compared with 71 patients (36.6%) in Group PF(>48 hours, ≤ 30 days) and 27 patients (29.7%) in Group PF>30 days (p = 0.515).
A substantial number of patients (169 cases, 37.2%) became pain free within the first 48 hours. The rate of hypesthesia was higher in patients who became pain free more than 30 days after GKS, with a statistically significant difference between patient groups (p = 0.014).
Constantin Tuleasca, Romain Carron, Noémie Resseguier, Anne Donnet, Philippe Roussel, Jean Gaudart, Marc Levivier and Jean Régis
The purpose of this study was to establish the safety and efficacy of repeat Gamma Knife surgery (GKS) for recurrent trigeminal neuralgia (TN).
Using the prospective database of TN patients treated with GKS in Timone University Hospital (Marseille, France), data were analyzed for 737 patients undergoing GKS for TN Type 1 from July 1992 to November 2010. Among the 497 patients with initial pain cessation, 34.4% (157/456 with ≥ 1-year follow-up) experienced at least 1 recurrence. Thirteen patients (1.8%) were considered for a second GKS, proposed only if the patients had good and prolonged initial pain cessation after the first GKS, with no other treatment alternative at the moment of recurrence. As for the first GKS, a single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 4–14 mm) anterior to the emergence of the nerve (retrogasserian target). A median maximum dose of 90 Gy (range 70–90 Gy) was delivered. Data for 9 patients with at least 1-year followup were analyzed. A systematic review of literature was also performed, and results are compared with those of the Marseille study.
The median time to retreatment in the Marseille study was 72 months (range 12–125 months) and in the literature it was 17 months (range 3–146 months). In the Marseille study, the median follow-up period was 33.9 months (range 12–96 months), and 8 of 9 patients (88.9%) had initial pain cessation with a median of 6.5 days (range 1–180 days). The actuarial rate for new hypesthesia was 33.3% at 6 months and 50% at 1 year, which remained stable for 7 years. The actuarial probabilities of maintaining pain relief without medication at 6 months and 1 year were 100% and 75%, respectively, and remained stable for 7 years. The systematic review analyzed 20 peer-reviewed studies reporting outcomes for repeat GKS for recurrent TN, with a total of 626 patients. Both the selection of the cases for retreatment and the way of reporting outcomes vary widely among studies, with a median rate for initial pain cessation of 88% (range 60%–100%) and for new hypesthesia of 33% (range 11%–80%).
Results from the Marseille study raise the question of surgical alternatives after failed GKS for TN. The rates of initial pain cessation and recurrence seem comparable to, or even better than, those of the first GKS, according to different studies, but toxicity is much higher, both in the Marseille study and in the published data. Neither the Marseille study data nor literature data answer the 3 cardinal questions regarding repeat radiosurgery in recurrent TN: which patients to retreat, which target is optimal, and which dose to use.
Jean Régis, Romain Carron, Michael C. Park, Outouma Soumare, Christine Delsanti, Jean Marc Thomassin and Pierre-Hugues Roche
The roles of the wait-and-see strategy and proactive Gamma Knife surgery (GKS) in the treatment paradigm for small intracanalicular vestibular schwannomas (VSs) is still a matter of debate, especially when patients present with functional hearing. The authors compare these 2 methods.
Forty-seven patients (22 men and 25 women) harboring an intracanalicular VS were followed prospectively. The mean age of the patients at the time of inclusion was 54.4 years (range 20–71 years). The mean follow-up period was 43.8 ± 40 months (range 9–222 months). Failure was defined as significant tumor growth and/or hearing deterioration that required microsurgical or radiosurgical treatment. This population was compared with a control group of 34 patients harboring a unilateral intracanalicular VS who were consecutively treated by GKS and had functional hearing at the time of radiosurgery.
Of the 47 patients in the wait-and-see group, treatment failure (tumor growth requiring treatment) was observed in 35 patients (74%), although conservative treatment is still ongoing for 12 patients. Treatment failure in the control (GKS) group occurred in only 1 (3%) of 34 patients. In the wait-and-see group, there was no change in tumor size in 10 patients (21%), tumor growth in 36 patients (77%), and a mild decrease in tumor size in 1 patient (2%). Forty patients in the wait-and-see group were available for a hearing level study, which demonstrated no change in Gardner-Robertson hearing class for 24 patients (60%). Fifteen patients (38%) experienced more than 10 db of hearing loss and 2 of them became deaf. At 3, 4, and 5 years, the useful hearing preservation rates were 75%, 52%, and 41% in the wait-and-see group and 77%, 70%, and 64% in the control group, respectively. Thus, the chances of maintaining functional hearing and avoiding further intervention were much higher in cases treated by GKS (79% and 60% at 2 and 5 years, respectively) than in cases managed by the wait-and-see strategy (43% and 14% at 2 and 5 years, respectively).
These data indicate that the wait-and-see policy exposes the patient to elevated risks of tumor growth and degradation of hearing. Both events may occur independently in the mid-term period. This information must be presented to the patient. A careful sequential follow-up may be adopted when the wait-and-see strategy is chosen, but proactive GKS is recommended when hearing is still useful at the time of diagnosis. This recommendation may be a main paradigm shift in the practice of treating intracanalicular VSs.