| A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | ||
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1 | Site/Stage | Workup | Treatment | Sim | Dose | Field | Chemo | Dosimetry | Timing | Notes | F/u | Outcomes | Adverse effects | Citations (full in reference tab) | |||||||||||||
2 | CNS | ||||||||||||||||||||||||||
3 | Updates Sept 2025: GOG 263, ASTRO 2025 PMRT guidelines, ESTRO oral cavity guidelines | ||||||||||||||||||||||||||
4 | General | H&P with neurologic assessment, IQ assessment. Give dexamethasone for symptoms (except in PCNSL). Keppra Imaging: CT, MRI brain Stereotactic guided biopsy CSF diversion if needed Post-op MRI in 24-72 hours Is spine eval needed? MRI spine and LP should be done pre-op. Otherwise post-op MRI spine can be done after 7-10 days (medullo, ependymoma, germ cell) Other labs: If suspecting germ cell tumor: CSF/serum analysis for AFP and beta-HCG, CSF cytology Functional tests: baseline neurocognitive function testing, visual field testing, pituitary panel. Consider audiology Peds functional tests: full ophto and endo consult, growth measurements, IQ measurements | supine, mask, fuse with preop and postop MRI images | Post op: contour GTV on T1 post contrast. Use pre-op MRI to assist with contouring; post-op cavity localization may be difficult, especially in cerebellum. Edema is best viewed on T2. Crop CTVs at natural boundaries such as ventricles and meninges. Tumors such as GBM may cross the corpus collosum. PTV: 3-5 mm per institution | optic nerves, chiasm max <54-55 (variation acceptable <60) Brainstem max <54 (VA max <60, D59 <10cc) cochlea mean <45 (VA 50-55) Retina mean <35 (VA < 50 Gy) Lens max <6-10 (VA < 15) Hippocampus max <6 Gy, V3 <20% Hippocampus (for 30 Gy IMRT WBRT) D100 <9 Gy, max <16 Gy Pituitary max <50 (VA <65) Lacrimal V30 <50, max <40 Pediatric (if different from above) Pituitary mean <25-30, max <42 Cochlea mean <35 (QUANTEC, Italian guidelines, International nasopharynx dose guidelines) | CSI: MB, Supratentorial PNET, Pineoblastoma, NGGCT, choroid plexus carcinoma. CSI if M+ only: Germinoma, Ependymoma, ATRT, CNS lymphoma. | QUANTEC, Bentzen et al, IJROBP, 2010 International Guideline on Dose Constraints for Nasopharyngeal Carcinoma, Lee, IJROBP, 2019 Italian CNS constraints, Scoccianti et al, Radiother Oncol, 2015 NCCN. Central Nervous System Cancers. | ||||||||||||||||||||
5 | Glioblastoma IDH-wt, age <70, good PS | H&P with neurologic assessment. Dexamethasone, keppra CT, MRI brain, stereotactic guided biopsy, surgery with maximal safe resection functioning tests: baseline neurocognitive function testing, visual field testing, pituitary panel. Consider audiology MGMT testing gives prognostic information. May help guide therapy in recurrence, elderly, or poor performance status F/u MRI 3 months later to help avoid appearance of pseudoprogression (more information in follow-up column and toxicity sheet) | EORTC: 60 Gy to single volume RTOG contouring is no better in a randomized trial (Liu, ASTRO, 2023) concurrent and adjuvant temodar Then Optune tumor treating fields after RT | EORTC: PTV: 60 Gy | Adjust CTV based on anatomical borders. Pay special attention to corpus callosum and cross CTV there if applicable. EORTC: PTV 60: add 2 cm margin to GTV (T1 enhancement + cavity) for CTV. Add 3-5 mm PTV and treat this single volume to 60 Gy. (ASTRO 2016, ESTRO-EANO, econtour.org) ESTRO-EANO 2023: 1.5 cm CTV + 3 mm PTV single volume If no flair on T2, add 2.5 cm to T1 enhancement plus cavity for the initial volume | unmethylated MGMT: temodar 75mg/m2 daily 7 days/week while on RT then 150 mg/m2 days 1-5 for q 28 day cycles x 6 months methylated MGMT: TMZ May follow with Optune tumor treating fields. Wear ≥18 hours per day. Begin after RT is complete and wear indefinitely. NCCN category 1 (EF-14), | Typically at least 2 week break after surgery | RANO criteria for pseudoprogression: To confirm progression within 3 months, there must be progression outside of the 80% isodose line. For pseudoprogression, repeat another scan sometime after 12 weeks. If increase in lesion size >25% of sum of perpendicular diameters, then progression has occurred MRI SPEC, MRI perfusion Biopsy if severe | MRI at 4 weeks after RT (2-6 weeks per NCCN) and then every 2-4 months for 2-3 years, then can reduce frequency Beware pseudoprogression: occurs within 3 months . Radiation necrosis occurs 3 months to years after RT. Occurs in 20-30%. Methylation of MGMT can more than double risk to 91% vs 41% | MS, any MGMT: 17 mos MS MGMT methylated: 22 mos MS MGMT unmethylated: 12 mos 2-yr OS 27%, 5-yr OS 10% (Stupp) With Optune, 5-yr OS 13% RPA 2010: RPA III: <50 yo and KPS ≥90, MS 17.1 mos, 1-yr OS 70%, 2-yr OS 20%, 5-yr OS 14% RPA IV: <50 yo and KPS <90, OR ≥50 yo, KPS ≥70, resection, and working MS 11.2 mos, 1-yr OS 46%, 2-yr OS 7%, 3-yr OS 4% RPA "V+VI": ≥50 yo, KPS ≥70, resection, not working OR ≥50 yo, KPS ≥70, biopsy only OR ≥50 yo, KPS <70 MS 7.5 mos, 1-yr OS 28%, 2-yr OS 1%, 3-yr OS 0% | NCCN. Central Nervous System Cancers. ESTRO-EANO guidelines Niyazi et al, Radioother Oncol, 2023 Liu et al, ASTRO, 2023 WHO 2021, Louis et al, Neuro Oncol, 2021 Stupp et al, Lancet Oncol, 2009 Stupp et al, JAMA, 2017, Hegi et al, NEJM, 2005 Avaglio, Chinot et al, NEJM, 2014 RTOG 0825, Gilbert et al, NEJM, 2014 NoA-09, Herrlinger et al, Lancet, 2019 RPA, Li et al, IJROBP 2010 Guo et al, JAMA Netw Open, 2023 RANO criteria for response assessment Wen et al, JCO, 2010 Pseudoprogression details Brandes et al, JCO 2008 Brandsma et al, Lancet Oncol, 2008 | ||||||||||||||||
6 | Glioblastoma IDH-wt, elderly or poor PS age >70 or KPS <60 per NCCN | Test for MGMT to help guide therapy If MGMT is not methylated, there is less benefit with TMZ | 40.05 in 15 fx (Roa) 34 Gy in 10 fx (Malmstrom) 25 Gy in 5 fx (IAEA) NCCN also has 50 Gy in 20 regimen listed Can test for MGMT to guide use of TMZ | 40.05 in 15 fx 34 Gy in 10 fx 25 Gy in 5 fx 50 Gy in 20 fx | Consider smaller margin than in conventional | Consider no chemo, TMZ alone, RT with adjuvant TMZ, or concurrent TMZ. May test for MGMT to guide therapy. If MGMT is unmethylated, there is little chemo benefit. | optics, retina, brainstem Max <40 Gy BED for 40 Gy/15 or 25 Gy/5 fx (IAEA) | Typically at least 2 week break after surgery | RT does provide survival benefit | IAEA: MS 6-8 mos PFS 4 mos | Perry et al, JCO, 2017 Malmstrom et al, JCO, 2010 Roa et al, JCO, 2004 Roa et al, JCO, 2015 WHO 2021, Louis et al, Neuro Oncol, 2021 | ||||||||||||||||
7 | Grade 4 Astrocytoma, IHD-mut | treat as glioblastoma | WHO 2021, Louis et al, Neuro Oncol, 2021 | ||||||||||||||||||||||||
8 | Grade 3 Oligodendroglioma with 1p19q codel | Test for 1p19q codeletion and IDH1 (oligoastrocytoma terms are now generally outdated, WHO 2021) | 59.4 Gy in 33 fx or 60 Gy in 30 fx Best evidence supports PCV. TMZ is also acceptable. | 59.4 Gy in 33 fx 60 Gy in 30 fx | GTV plus 1.5 cm margin | PCV (procarbazine, CCNU (lomustine), vincristine) for codel (RTOG 9402) Or concurrent+adjuvant TMZ | Typically at least 2 week break after surgery | Codel Median OS 13-14 yrs As of WHO 2021, any IDH-wt is now defined as glioblastoma | ESTRO-EANO guidelines 2024 WHO 2021, Louis et al, Neuro Oncol, 2021 NOA-04, Wick et al, JCO, 2009 DeAngelis et al, JCO, 2009 Wick et al, Neuro Oncol 2016 NCCN. Central Nervous System Cancers. Lassman et al, JCO, 2022 | ||||||||||||||||||
9 | Grade 3 Astrocytoma without 1p19q codel | Test for 1p19q codeletion and IDH1 (oligoastrocytoma terms are now generally outdated WHO 2021) | 59.4 Gy in 33 fx or 60 Gy in 30 fx Best evidence supports adjuvant TMZ (not concurrent). Concurrent TMZ and adjuvant PCV also acceptable. | 59.4 Gy in 33 fx 60 Gy in 30 fx | GTV plus 1.5 cm margin (CATNON) | Adjuvant TMZ (CATNON), or consider concurrent+adj TMZ, though no benefit yet with concurrent TMZ on CATNON Or adjuvant PCV | Noncodel IDHmut OS 5-8 yrs As of WHO 2021, any IDH-wt is now defined as glioblastoma | ESTRO-EANO guidelines 2024 WHO 2021, Louis et al, Neuro Oncol, 2021 NOA-04, Wick et al, JCO, 2009 Wick et al, Neuro Oncol 2016 CATNON, van den Bent et al, JCO, 2019 NCCN. Central Nervous System Cancers. Lassman et al, JCO, 2022 | |||||||||||||||||||
10 | Grade 2 glioma (astrocytoma and oligodendroglioma) | Surgery first (Goal of "Maximal Safe Resection", ideally GTR). Radiation indications: age >40 or subtotal resection (RTOG 9802). Or 3/5 "SATAN" criteria: age ≥40, astrocytoma, crosses midline, size >6 cm, pre-op neuro function status >1 (EORTC & RTOG 0424) Treat unresected with radiation | 50.4-54 Gy in 28-30 fx NCCN: 45-54 Gy | 50.4-54 Gy in 28-30 fx | GTV (including FLAIR/T2) + 1 cm (ESTRO/EANO) Pediatric low grade glioma: CTV 5 mm plus PTV | category 1: PCV x6 (procarbazine, CCNU (lomustine), vincristine) now used based on long term results of RTOG 9802 showing survival benefit Or TMZ Test for 1p19q codeletion and IDH1. These more likely benefit from chemo | MRI q 3-6 mo x 5 years then annually | pure oligo - 14 yr low grade astro -5 y 3-5 SATANS criteria - MS 8 yrs and 3-yr OS 75% in RTOG 0424 w TMZ (MS 3.5 yrs in EORTC with no chemo) EORTC 22845 - RT improves PFS from 3.4 to 5.3 years, but not OS 0-2 SATANS criteria - MS 8 yrs (EORTC. TMZ unknown) As of WHO 2021, any IDH-wt is now defined as glioblastoma | ESTRO-EANO guidelines 2024 WHO 2021, Louis et al, Neuro Oncol, 2021 RTOG 9802, Shaw et al, JCO, 2008 Buckner et al, NEJM, 2016 NCCN. Central Nervous System Cancers. Believers EORTC, Karim et al, IJROBP, 1996 Pignatti et al, JCO, 2002 RTOG 0424, Fisher et al, IJROBP, 2015 ACNS0221, Cherlow et al, IJROBP, 2019 | ||||||||||||||||||
11 | Ependymoma of spine | 50.4 Gy NCCN: For GTR: consider treatment if myxopapillary grade 1 or 2, or observe May observe grade 1 or 2, non-myxopapillary Treat anaplastic or subtotal resection of any grade Per NCCN these rules also apply to intracranial ependymoma | 50.4 Gy | 1.0-1.5 cm margin superiorly and inferiorly, can include nerve roots radially | None for peds or adults. RT should be immediate in all peds ages (from ACNS 0121, Merchant et al, JCO, 2019) | Weber et al (adults) GTR alone 10-yr LC 56%, TTF 4.75 yrs GTR+RT 10-yr LC 92%, TTF 10.5 yrs STR 10-yr LC 0% STR+RT 10-yr LC 65% ACNS0121 (peds) GTR of grade I-II then observation: 5-yr EFS 61% STR then RT: EFS 37% nearGTR then RT: EFS 69% Anaplastic then RT 5-yr EFS 61% | NCCN. Central Nervous System Cancers. Weber et al, Neuro Oncol, 2015 ACNS 0121, Merchant et al, JCO, 2019 | ||||||||||||||||||||
12 | Ependymoma of brain | See above Pre assessment functioning: IQ test, audiology, hormone levels, visual field testing, fundoscopic exam, endocrine consult, measure growth Pre-op MRI spine and LP with CSF cytology, preop and postop MRI brain within 24-72 hr. Or MRI spine can be done post-op after 7-10 days | On NCCN indications for adjuvant RT are identical as for spine. Some especially advocate observation for supratentorial Treat with 54 Gy then boost to 59.4 CSI only if CSF+ or MRI+. Give 36 Gy to CSI with boost to gross spine disease of 45 Gy | anesthesia if needed for peds supine, face mask, CT sim, fuse with preop and postop MRI images | PTV1: 54 Gy PTV boost: 5.4 Gy (total 59.4 Gy) Optional PTV CSI: 36 Gy 54 Gy only for age <18 mos | MRI fusion Outline GTV (pre-op MRI helps to assess the originaly location of tumor) with 0.5-1 cm CTV then 0.3-0.5 cm PTV. Boost volume comes off the cord The boost volume is often not much smaller in size than the initial volume | MRI brain q 3-4 mo x 1 yr then q 4-6 mo for second year, then q 6-12 mo | With RT: 5-yr DFS 50% 5-yr OS 70% | Ducassou et al, SFCE, IJROBP, 2018 NCCN. Central Nervous System Cancers. | ||||||||||||||||||
13 | Pituitary tumor | H&P, ophtho consult/visual field testing, endocrine labs and consult (TSH, GH, IGF-1, ACTH, FSH/LH, glucose, PRL), MRI brain Labs for specific tumors: GH secreting: GH>10, elevated IGF-1 (aka somatomedin C). Can give glucose challenge if unsure, which should cause GH to fall. IGF-1 is best for f/u, not dx PRL: PRL>20, often>100 Cortisol: Elevated cortisol on overnight dexamethsone surpression test, 24 hour urinary free cortisol. If suspecting ectopic ACTH, then ACTH has to be measured in petrosal sinuses to confirm Cushings | All tumors except prolactinoma: Transphenoidal surgery first. Second line is medical therapy (more info to right) Prolactinoma: first line treatment is bromocriptine or cabergoline, even if visual symptoms. If medical therapy fails, surgery is next line RT is indicated for inoperable tumors or failure after STR. Discontinue medical management during RT. All TSH: surgery then adjuvant 54 Gy others: 50.4 Gy 18-20 Gy SRS for nonfunctional 20-25 Gy SRS for functional | anesthesia if needed for peds supine, face mask, CT sim, fuse with preop and postop MRI images | IMRT 50.4 Gy (54 Gy for TSH) SRS 18-20 Gy nonfunctional 20-25 Gy functional | GTV + PTV margin | PRL - cabergoline, (preferred before surgery for this type only). Reduces size in 80%. Can use for 2 years then stop and follow. ACTH - ketoconazole, mitotane, metapyrone (not as effective as surgery) GH - octreotide, lanreotide. In those that do not respond to surgery, 50-60% success rate. Pegvisomat (IGF-1 blocker) is 97% effective but 150k per year cost | Gunderson PRL: biochemical control 15-30% at 3-6 yrs f/u Acromegaly EBRT: 5-yr biochemical remission 30%, 10-yr 50%, 15-yr 70% Acrometaly SRT IGF-1 normalization 50-60% at about 6 yr f/u Cushings disease: Cortisol normalization 40-50% at 5 years Perez - hormone control: PRL 30%, GH 80%, ACTH 50-80%, TSH <1%. Of all pituitary tumors Lag time for recovery: PRL 5-10 yrs, GH 50% in 2 yrs and 75% in 5 yrs, ACTH 2 yrs Epidemiology PRL 50%, GH 20%, ACTH 25%, TSH 1% SRS may speed response (1-2 yr vs. 2-10yr) and better LC ~90% | 50% will develop some sort of pituitary dysfunction. Order of sensitivity of hormones: 1) GH, 2) FSH/LH, 3) TSH/ACTH | Gunderson&Tepper. Pituitary Tumors and Craniophayngiomas. Leibel and Phillips: Pituitary Tumors. Loeffler et al, J Clin Endocrinol Metab, 2011 Minniti et al, Radiat Oncol, 2016 Kim et al, Surg Neurol Int, 2012 | |||||||||||||||||
14 | Primary CNS lymphoma | MRI suggestive of lymphoma (shows multiple enhancing periventricular masses). Do not use dexamethasone upfront if possible Biopsy prior to steroids CSF testing (1/3+) spine MRI if CSF+ slit lamp eye exam Labs: CBC, CMP, HIV test, EBV titer Standard NHL workup: CT of C/A/P, PET (consider BM bx, testicular US for men >60. These are category 2B recs) Imaging findings: radiopedia: "a mass or multiple masses usually in contact with subarachnoid/ependymal surfaces, can often cross corpus collosum, homogeneous and intense enhancement (a low grade lymphoma may have less enhancement). Even with larger lesions there is little mass effect or edema" | Steroids after biopsy. Most first do chemo alone and no RT. If planning on RT, use a high dose MTX regimen 3.5g/m2, R-MCVP. If thinking of deferred RT, give M-R, 8mg/m2. Only use IT MTX if CSF or spine involvement. Most only give RT with relapse. CR to chemo: 1) consolidation high dose chemo and autologous SCT 2) or other chemo 3) or low dose RT. Give 23.4 Gy to whole brain plus C1-C2 and posterior eyes <CR to chemo: 1) more chemo 2) or RT to 45 Gy/1.8 to focal disease. "Lower doses are less toxic and may be just as effective" NCCN. KPS <40: WBRT or chemo alone Recurrence: 1) HD ara-C 2) or WBRT if not given previously and one year has passed age >60: try to avoid RT due to toxicity. If relapse, use MTX again in attempt to avoid RT eye exam positive: RT to globe or intraocular chemo (category 2B) CSF positive: IT chemo (category 2B) | 23.4-45 Gy | Cover postior half of globe in WBRT. If eye is positive, then cover entire eye. | Avoid dexamethasone upfront if feasible If planning deferred RT M-R, methotrexate 8 mg/m2 high dose MTX based chemo for 5-7 cycles Methotrexate 3.5mg/m2 over 2 hours, procarbazine, cytarabine, vincristine) (R-MCVP) Second line therapy HD MTX alone or HD ara C. Can give RT if >1 year has passed and not given before For HIV+ give HAART | PCNSL becomes ocular in 25% (50-75% primary ocular will become CNS lymphoma) Median OS 7.5 yrs 2-yr OS 80% 60% have CR (RTOG 0227 and 9310) | NCCN. Central Nervous System Cancers. radiopedia. Primary CNS lymphoma. NRG RTOG 0227, Glass et al, JCO, 2016 RTOG 9310, DeAngelis et al, JCO, 2002 Practice Patterns Fallah et al, Blood Adv, 2016 | |||||||||||||||||||
15 | Meningioma | MRI: thickening of meninges Post-op dotatate PET Biopsy not required if radiologic diagnosis is clear and tumor is in a critical location Treatment options: observation first, then surgery for progession or large tumor or tumor in important location. RT is also an option over surgery upfront Indications for RT: NCCN: >3cm and unresectable, or STR of large lesion, or unresectable small lesion at risk of neuro sx, or grade 2-3 RTOG 0539: All grade II GTR, any recurrent of any grade, all grade III | Maximal safe resection 50.4-54 Gy 14-16 Gy SRS Optic nerve: 50.4 Gy Grade 2: 54-60 Gy Grade 3: 59.4-60 Gy Consider giving 60 Gy to grade 2 if subtotal resection (RTOG 0539) | IMRT 50.4-54 Gy in 30 fx SRS 14-16 Gy Grade 3 60 Gy | Grade 1: usually 0 CTV. Do not include dural tails (this is hypervascular dura, not tumor) Grade 2: 0-5 mm CTV. Practices vary. Grade 3: 1-1.5 cm CTV? RTOG 0539 CTVs: (these have been criticized by some as too large) grade 1: GTV + 0.5 cm CTV (some don't add CTV for grade 1) grade 2: GTV + 1cm CTV (many use smaller CTV) grade 3: GTV +2 cm CTV to 54 Gy with boost to 1 cm CTV margin to 60 Gy (many use smaller CTV 3-5 mm PTV | Benign - <4 mitoses per HPF, atypical 4-19 mitoses per HPF, malignant >20 Simpson grade Grade 1: Removal of tumor bulk, surrounding dura, involved bone. 5-yr recurrence 10% Grade 2: Removal of tumor with diathermy of involved dura. 5-yr recurrence 20% Grade 3: Small focus left in situ. 5-yr recurrence 30% Grade 4: Macroscopic residual disease. 5-yr recurrence 40% Grade 5: Simple decompression | Low risk (grade I GTR and STR) 3-yr LC 94% 5-yr LC 88% Intermediate risk (grade II GTR, grade I recurrent) 3-yr LC 95% recurrent grade II 5-yr LC 30% grade III 5-yr LC 70% (RTOG 0539) | NCCN. Central Nervous System Cancers. RTOG 0539 Rogers et al, ASTRO, 2016 Rogers et al, Neuro Oncol, 2017 Rogers et al, IJROBP, 2019 Pollock et al, IJROBP, 2012 NRG BN003 (NCT03180268) PET planning Perlow et al, IJROBP, 2024 | |||||||||||||||||||
16 | Whole brain IMRT hippocampal sparing | On MRI observe that lesions aren't too close to hippocampus to preclude sparing Sparing of one side may be acceptable; however, any benefit of this is unknown | 30 Gy/ 10 fx arc based IMRT Memantine | 30 Gy/10 fx | PTV 0-5 mm (PTV was 0 on NRG-CC001) | Memantine | Hippocampi D100% <9 (VA 10) Max <16 (VA 17) Optics max <30 Gy (VA <37) Cochlea and middle ear also feasible to spare (constraint unknown) PTV D2% < 37.5-40 D98% > 22.5-25 V30 Gy > 90-95 Ensure also that GTVs aren't undercovered near hippocampi | Should the parotid be contoured? No. When using VMAT or tomotherapy, which are required to meet constraints, the parotid will be avoided without concern. | NRG CC001, Brown et al, JCO, 2020 | ||||||||||||||||||
17 | gliomatosis cerebri | Glioma with diffuse infiltration of brain WHO 2016: GC is not a distint pathologic entity. GC is a pattern of spread of a grade III or IV glioma | No consensus on best approach 54-59.4 Gy focally or 20-54 Gy whole brain | 54-59.4 Gy/ 1.8 focal or 20-54 Gy WBRT | NCCN. Central Nervous System Cancers. Ranjan, et al, Front Oncol, 2017 WHO 2016, Louis et al, Acta Neuropathol, 2016 | ||||||||||||||||||||||
18 | Recurrent glioblastoma | RTOG 1205: up to 3rd relapse, size ≤6 cm, and multifocal recurrences of total size ≤6 cm. In and out of field recurrences permitted. Any interval after RT allowed. <6 months permitted if out of field, or biopsy proven in field, or conclusive on imaging. If within <3 months, consider possibility of pseudoprogression or radiation necrosis. Consider biopsy, MRI spec, MRI perfusion, or PET (see radiation necrosis section in toxicity tab) RANO criteria for pseudoprogression: To confirm progression within 3 months, there must be progression outside of the 80% isodose line. For pseudoprogression, repeat another scan sometime after 12 weeks. If increase in lesion size >25% of sum of perpendicular diameters, the progression has occured | Focal -IMRT 3.5 Gy x 10 with bev -SRT 11 Gy x 3 qod -SRS -surgery -Optune -IFN-α for unmethylated -chemo Large or diffuse -TMZ (esp for methylated) -Other types of chemo -bevacizumab -Optune -IFN-α for unmethylated | IMRT 3.5 Gy x 10 (RTOG) with bev SRT 11 Gy x 3 qod (MSKCC) SRS 16-24 Gy | No CTV, except 5mm CTV optional for lesions ≤3.5 cm or new lesions (RTOG 1205) | Begin after staples are removed if surgery | NCCN. Central Nervous System Cancers. EF-11, Stupp et al, Eur J Cancer, 2012 iRANO pseudoprogression Clarke et al, IJROBP, 2017 RTOG 1205, Tsien et al, JCO, 2022 EORTC 26101, Wick et al, NEJM, 2017 IFN-α, Guo et al, JAMA Netw Open, 2023 Radiopedia. Cerebral radiation necrosis. | ||||||||||||||||||||
19 | Chordoma (chondroid or classic) | 70-80 GyE protons for unresectable or positive margins | 70-80 GyE protons | consider 0.5 cm CTV sup/inf | 50% sacrococcyx, 35% BOS | 5-10 yr LC 50% | NCCN. Central Nervous System Cancers. | ||||||||||||||||||||
20 | Hemangiopericytoma | May intensely enhance like meningioma. No calcifications. Bone erosion may be present. Staging with CT C/A/P. Tumor may metastasize to lung, liver, bone, etc. Metastasis can occur up to 5 years later. | Surgery. RT to 45-60 Gy even for GTR. SRS/SRT is an option for small lesions. | 45-60 Gy | Without RT: 10-yr DM 25% 10-yr LR 72% 15-yr LR 90% RT decreases recurrence by at least 1/3 and much more in some series | Shiariti et al, J Neurosurg, 2011 Ciliberti et al, Oncol Rev, 2018 | |||||||||||||||||||||
21 | Graves opthalmopathy | RT should be given in first year. If RT is given in a "burnt out" or inactive Graves, it is unlikely to have an effect first try artificial tears, protective shades, steroids, Teprotumumab. Another option is surgical decompression | 20 Gy in 10 fx | 20 Gy/ 10 fx | opposed laterals and block lens and cornea | Teprotumumab (IGF-IR inhibitor) | Peterson et al, Standford, IJROBP, 1990 Douglas et al, NEJM, 2020 | ||||||||||||||||||||
22 | Pseudotumor of orbit | Mature polyclonal lymphocytes noted. First line tx: steroids. RT used for recurrence or intolerance of steroids | Treat like Graves as above | 20 Gy/ 10 fx | 80% CR/PR (55% stopped steroids and 25% decreased steroid use) | Matthiesen et al, IJROBP, 2011 | |||||||||||||||||||||
23 | Uveal melanoma LDR Eligibility: essentially any except extension outside the eye >5 mm or no useful vision | H&P: loss of vision, floaters, flashing lights, pain, etc. Complete ophto evaluation. Measure diameter and thickness of tumor, location, geometry, color (fundus photography and ocular US) Biopsy not required Labs: CBC, LFTs, LDH Imaging: fundus photography, ocular US, MRI Staging imaging: if LFTs elevated then order CT of chest/abdomen allowable, but poorer vision and LC outcomes: peripapillary, subfoveal, exudative retinal detachments not suitable: T4e or >5 mm extraocular extension, large basal diameters, blind painful eyes, no light perception | 85 Gy I-125 LDR (practices vary) For tumors near optic nerve, adding laser or EBRT to plaque may be of benefit to compensate for low coverage | First refer for US mapping of the eye with ophthalmologist to create a fundus diagram, mapping out clock location and diameter of tumor and proximity lens, optic nerve, and fovea. Using planning system, prescribe 85 Gy to apex with 100% of dose covering the tumor with a 1-3 mm margin. Load seeds symmetrically and with seeds with all same activity to avoid errors of having plaque placed upside down or flipped. With larger tumors, may need to rx beyond apex. Curve isodose lines around optic nerve and fovea Take patient to OR and place under general anesthesia. Open and peel back the sclera, moving the eye by anchoring the ocular muscles -Locate the tumor with transillumination and mark position with tissue dye marker -Suture dummy into place and confirm position with US -Suture radioactive plaque -Irrigate eye with antibiotic solution, close conjunctiva, place lead eye shield -Plaque stays in place for 3-7 days depending on dose rate. Can be inpatient or outpatient at this time depending on license | LDR 85 Gy I-125 | Limit optic nerve and fovea to 50 Gy | COMS: For medium tumors, 5-yr LF 10%, 5-yr eye retention 85%, 12-yr CSS 80% 60% of patients who died had DM | RT retinopathy up to 43% (depends on the length of follow-up), optic atrophy, cystoid macular edema, cataracts, vitreous hemorrhage, neovascular glaucoma, central retinal vein occlusion, scleral necrosis, secondary strabismus (5%) | ABS guidelines, Brachytherapy, 2014 COMS, JAMA Ophthalmol, 2006 | ||||||||||||||||||
24 | Focal brainstem glioma | Features: WHO grade I or II, well circumscribed, located in medulla or brainstem. Focal brainstem glioma occur outside of pons typically and are of lower grade than diffuse pontine glioma (DIPG). | Surgery is indicated for focal, exophytic, or cervicomedullary tumors. Surgical techniques have improved. Consult NS regarding resectability. RT for STR or unresectable. 54 Gy with 0.5-1 cm margin. SRS or SRT sometimes also used. | 54 Gy | UpToDate. Focal Brainstem Glioma. Sabbagh and Alaqeel, Neurosciences, 2015 | ||||||||||||||||||||||
25 | Diffuse intrinsic pontine glioma (pediatric) | Features: tumor of pons, age 5-9. High grade. Most omit biopsy, though some will perform. Radiology: DIPG has both hyper- and hypo-intense regions. Cover both in GTV. | 54-59 Gy Hypofractionation: 39 Gy/ 13 fx 45 Gy/ 15 or 17 fx Reirradiation: 24 Gy /12 fx | 54-59 Gy Hypofx 39 Gy/ 13 fx 45 Gy/ 15 or 17 fx | DIPG tumor has both hyper- and hypo-intense regions. Cover both in GTV. Take care to observe for unusual extensions of tumor. Contouring difficulty can be high. Confer with radiology. 1.0 cm CTV (some larger, practices vary) | none | Median OS 10 months and 2-yr OS 10% with RT | COG-ADVL 1217 Zaghoul et al, IJROBP, 2018 CTV margin Tinkle et al, IJROBP, 2019 Reirradiation Janssens et al, Eur J Cancer, 2017 Amsbaugh et al, IJROBP, 2018 | |||||||||||||||||||
26 | Low grade glioma (includes pilocytic astrocytoma) (pediatric) | Well circumscribed mass. Typically age <20 Often occurs in cerebellum, near brainstem, hypothalamus, or optic chiasm, though can occur in any part of brain | Surgery. Observation is an option, even for residual disease RT can be used for residual disease, progression, or recurrence. Trial chemo first for age <10 54 Gy/ 30 fx | 54 Gy | CTV 0.5 cm PTV 0.3 cm GTV: contour pre-chemo extent of disease, adjusting for shrinking borders, even in areas of apparent CR; microscopic residual disease could still be present. Use all sequences (T2, FLAIR) to identify residual areas of disease. Contouring difficulty level can be high. | if less than 10 years old, trial carbo/vincristine before RT | 5-yr OS 93% 5-yr PFS 70% | ACNS0221, Cherlow et al, IJROBP, 2019 | |||||||||||||||||||
27 | Optic glioma (pediatric) | Diagnosis by MRI - no bx necessary. These are typically pilocytic astrocytomas A pediatric tumor in age 18 or less, often age <10 (Optic meningiomas: occur in age ≥20 with "tram tracking" on nerve) | observe until progression. 50.4 Gy In children age <10 use carbo/vincristine when progression is noted, then RT for failure. If age >10, use RT for progression | 50.4 Gy | CTV 0.5- 1.0 cm. Consider tracing along optic nerve PTV 0.3 cm GTV: contour pre-chemo extent of disease, adjusting for shrinking borders, even in areas of apparent CR; microscopic residual disease could still be present. Use all sequences (T2, FLAIR) to identify residual areas of disease. Contouring difficulty level can be high. | carbo/vincristine in age <10. RT only for progression | Max dose <54 Gy | no biopsy, p/w visual loss, 30% have NF1 stigmata, 25% of NF1 patients develo OPG, chiasm more common than nerve | 90% OS at 5-10 years, LC only 70-80% if chiasmatic/hypothalamic and OS only 50-80% for those tumors | Jahraus et al, Pediatr Blood Cancer, 2006 | |||||||||||||||||
28 | CSI 3D | MRI brain (include FIESTA sequence), C, T, L, S spine | Per histology treat craniospine to 23.4-36 Gy and boost with IFRT to 50.4, 54, 55.8, or 59.4 Gy | anesthesia if needed for peds Simulate prone vs. supine: Benefits of supine: more comfort, easier anesthesia access, less film rejections Benefits of prone: matching and initial sim setup may be easier hyperextension of chin, face mask, CT sim thin slice, fuse with MRI brain FIESTA sequence, post-op and pre-op brain MRI Oral narrative 3D: I would simulate the patient in the prone/supine position. The superior border of the spine field would be located between C2-C5 and would be chosen to avoid divergence through the oral cavity. This would extend inferiorly to S2/S3 as seen on MRI with lateral borders 1-1.5 cm from the vertebral body. (Optional: I would cover the entire vertebral body to account for growth changes.) To match the cranial fields to the spine fields I would angle the collimator of the cranial fields and kick the couch toward the beam. [If the patient requires two spine fields] I would match at the posterior vertebral body, below L1, and add appropriate skin gap. At the junction of the cranial and spine fields I would match anterior to the cord (to create a cold match). I would feather the fields 1 cm every 9 Gy. | Per tumor type CSI 23.4 or 36 Gy IFRT boost 50.4, 54, 55.8, or 59.4 Gy | Boost = post-op tumor bed +1 CTV with 0.3-0.5 cm PTV. 2D borders: Superior border: ~C2-C5 (limited by shoulders; avoid divergeing spine field into oral cavity) to inf ~S2/S3 (locate on MRI), lateral 1-1.5 cm margin on vertebral body. Rx to posterior vertebral body (spinal cord). Can cover entire vertebral body if younger for concern for abnormal bone growth If >100 SSD or 2 fields, match at posterior vertebral body skin gap = d/2(L1/SSD1 + L2/SSD2) First junction is between neck and shoulders (avoid shoulders with laterals, avoid oral cavity with spine field). Match diverging fields anterior to the cord. Start at shoulder and feather junction superiorly 0.5-1 cm weekly or every 9 Gy. Second junction should be placed below L1, i.e. below end of cord. Angle collimator 10 degress to match spine fields =arctan(1/2 length of spine field / SSD) Kick couch 8 degrees feet toward beam (breast is away)= arctan (1/2 length of cranial field / SAD) Alternatively, avoid couch kick and rotation with half beam block of superior spine field if enough space. Must half beam block both. If only blocking one, must still either rotate or kick | Ajithkumar et al, SIOPE consensus guidelines, Radiother Oncol, 2018 Khan's The Physics of Radiation Therapy Mahajan and Paulino, Radiation Oncology for Pediatric CNS tumors, Chapter 27 Eaton et al, 2018 | ||||||||||||||||||||
29 | CSI IMRT contouring | Supine with mask Oral narrative IMRT: I would use IMRT, contouring all areas of potential CSF extension according to SIOPE guidelines including whole brain, cribiform plate, optic nerves, skull base foramina, pituitary fossa, cord and nerve roots in the C, T, and L spine, down to thecal sac in sacral spine as determined by MRI. I would use arc planning to cover the volume. | Per tumor type CSI 23.4 or 36 Gy IFRT boost 50.4, 54, 55.8, or 59.4 Gy | Contour entire extent of CSF. This includes whole brain, cribiform plate, pituitary fossa, optic canal, optic nerves, superior orbital fissure, foramen rotundum, foramen ovale, IAC, hypoglossal canal, and jugular foramen. Include the nerve roots in the C, T, and L spine. (There is no CSF in the S nerve roots.) Use T2 MRI to locate the thecal sac, usually near S2-3 but can be more inferior. Confirm visually that all areas are covered by isodose lines (it is possible for an arc algorithm to undercover areas such as optics and still achieve 95% coverage) PTV per institution. May need ~0.7-1 cm PTV for spine | Ajithkumar et al, SIOPE consensus guidelines, Radiother Oncol, 2018 | ||||||||||||||||||||||
30 | Medulloblastoma (pediatric), standard risk (age >3, <1.5 cm2 residual, M0) | Steroids and Keppra. MRI brain, total spine, and LP. MRI brain must be done pre-op and post-op within 48 hours. MRI spine can be done pre-op or 7-10 days after surgery. LP can be done pre-op or post-op greater than 10 days after surgery. Attempt gross total resection. Can also do stereotactic biopsy alone. May need CSF diversion. MRI spine and LP may be done post op after 7-10 days. Pre-op is preferred Pre assessment functioning: IQ test, audiology, hormone levels, visual field testing, fundoscopic exam, endocrine consult, measure growth | "maximal safe resection" ---> 23.4 Gy CSI then 54 Gy IFRT boost to tumor bed, all with 1.8 Gy per fraction Up to 55.8 Gy. Consider 55.8 Gy for M+ or >1.5 cm residual Concurrent vincristine and adjuvant cis/CCNU/vinc (If no vincristine given then use 36 Gy CSI) | see CSI section above | CSI 23.4 Gy IFRT boost to 54 Gy | see CSI section above | Vincristine concurrently 6 weeks after RT --> cisplatin, CCNU aka lomustine, and vincristine COG ACNS0331 alternates above chemo with vincristine/cyclophosphamide/mesna, 9 cycles total (AAB, AAB, AAB) | Start RT within 31 days after surgery | 50-60% age 5-9, 2nd peak age 20-30 yo, steroids and ventricular drain | Posterior fossa syndrome in 22%. Occurs 1-2 days after surgery. Mnemonic SAME: swallowing dysfunction, ataxia, mutism, emotional lability. If this appears, continue with aggressive treatment as planned | Standard risk: 5yr EFS = 83% 10-yr EFS 76% (packer) PF failuree = 5% 80% OS High risk: 5 yr EFS 67% Outcomes are similar with adults | secondary malignancy, infertility, neurocognitive changes, decreased bone growth (decreased sitting height), endocrinopathies (GH first to go), precocious puberty, hearing loss 10-yr incidence of secondary malignancy: 4% | ACNS0331, Friedman et al, Pediatr Blood Cancer, 2017 Chemo Packer et al, JCO, 2006 Tait et al, Eur J Cancer, 1990 Massimino et al, Crit Rev Oncol Hematol, 2016 | ||||||||||||||
31 | Medulloblastoma (pediatric), high risk (age <3, >1.5 cm2 residual, or M+), or supratentorial PNET | surgery ---> 36 Gy CSI-->55.8 Gy boost to whole posterior fossa (some may boost to IFRT field) Boost gross disease in spine to 45 Gy if above terminus of spinal cord and 50.4 Gy if below terminus of spinal cord If diffuse gross disease of cord, boost to 39.6 Gy (ANCS 0332) | see CSI section above | CSI 36 Gy IFRT boost to 55.8 Gy | Current protocol recommends boost to whole posterior fossa for high risk | cisplatin/vincristine/cyclophosphamide x 6 cycles | OS = 60% | vincristine causes constipation/abdominal pain and neuropathy | ACNS0332 (NCT00392327) | ||||||||||||||||||
32 | Medulloblastoma age<3 | Treat with chemo alone to delay radiation until age >3 yo if possible. Treat with RT for progression or M+ disease | see CSI section above | 58% will require RT, but EFS only 32% | Lassaletta et al, Lancet Oncol, 2018 | ||||||||||||||||||||||
33 | Non-medulloblastoma embryonal tumors (NMBET) [includes supratentorial PNET, pineoblastoma, ependymoblastoma, embryonal tumors with multilayered rosettes (ETMR)] (pediatric) | see medulloblastoma Special case: pineal location. Also perform visual history and exam to investigate possible trilateral RB. Pineal location leads to compromise of superior colliculus: vertical gaze palsy, pupillary and oculmotor nerve paresis (Parinaud's), convergence/retraction nystagmus, Pseudo-Argyll Robertson pupils, eyelid retraction, conjugate down gaze (setting sun) | Treat like medulloblastoma (often treat as if high risk, though some treat as if standard risk) CSI to 36 Gy then boost to 54-59.4 Gy Some may treat with 23.4 Gy CSI, especially if favorable risk or also getting ASCT Consider boosting spine mets an extra 4-5 Gy | see CSI section above | CSI 36 Gy IFRT boost to 54-59.4 | see CSI section above | per medulloblastoma | Non-medulloblastoma embryonal tumors (NMBET) is the entity categorization now per WHO 2016 (terms such as PNET, ependymoblastoma, etc are no longer included in WHO 2016) | 5-yr OS 30-50% 5-yr EFS 40-60% | ACNS0334 (NCT00336024) McGovern et al, AT/RT and EMTR. In Mahajan and Paulino, Radiation Oncology for Pediatric Brain Tumors. WHO 2016, Louis et al, Acta Neuropathol, 2016 Jakacki et al, Pediatr Blood Cancer, 2015 | |||||||||||||||||
34 | Atypical teratoid rhabdoid tumor (AT/RT) (pediatric) | see medulloblastoma Ages 0-4 | Sequencing (ACNS0333): *Surgery *Induction chemo *high dose consolidation Thio/Carbo *RT: CSI + IFRT (CSI optional) *ASCT Gross tumor/tumor bed: 50.4 or 54 Gy CSI: 23.4 or 36 Gy (encouraged but optional on ACNS0333) Consider lower doses for age<3 or standard risk per medulloblastoma If diffuse spinal involvement, can give 39.6 Gy to spine. If focal spine disease, may boost it to 45 Gy. ESTRO-SIOPE guidelines *CSI only for metastatic disease *CSI to 35.2 - 36 Gy for age >36 mos *CSI optional in age <36 mos to 23.4/24 Gy *54 Gy boost is recommended. Consider 50.4 Gy in some cases, such as age <36 mos *Boost metastasis to 45-50.4 Gy | see CSI section above | CSI 23.4 or 36 Gy IFRT boost to 50.4 or 54 Gy | Induction chemo with VCR/CDDP/CTX/VP16/MTX Followed by consolidation with Thio/Carbo/ASCT | 4-yr EFS 35% 4-yr OS 45% ACNS0333 | ESTRO-SIOPE, Timmermann et al, Radiother Oncol, 2024 ACNS0333, Reddy et al, JCO, 2020 McGovern et al, AT/RT and EMTR. In Mahajan and Paulino, Radiation Oncology for Pediatric Brain Tumors. | |||||||||||||||||||
35 | Germinoma (pediatric) | Imaging: MRI brain, MRI spine, CT, stereotactic guided biopsy Labs: CSF/serum analysis for AFP and beta-HCG, cytology of CSF. BHCG can be normal or up to 75 in Germinoma. AFP always normal in germinoma. Only a sample is needed; no need for maximal resection. Surgery can cause morbidity. Biopsy not required if >100 BHCG or high AFP and meets imaging criteria per current protocol Per ACNS 1123: Germinomas: AFP and β-hCG 5-50 (biopsy not required), patients with bifocal involvement or pineal lesion with DI and β-hCG ≤ 100 (biopsy not required, as presumably multifocal), or biopsy proven germinoma or mixed with mature teratoma. Third ventriculoscopy for hydrocephalus: entails opening in floor of 3rd ventricle to prepontine space (no VP shunt needed). If performed, must include prepontine cistern in RT volume Funtioning: optho consult, endocrine consult After chemo, what if there is if PR or progressive disease? Perform 2nd look surgery to look for possible mature teratoma or NGGCT. If mature teratoma is found, continue treating like pure germinoma. If NGGCT is found, treat like NGGCT. | Some treat with induction chemo first and then reduced RT dose for CR. Some argue this should only be done on trial. If CR to chemo, treat to 21 Gy to whole ventricles + 9 Gy boost = 30 Gy If PR to chemo or no chemo: 24 Gy to whole ventricles + 21 Gy boost = 45 Gy. Use 1.5 Gy per fx If +CSF or multiple midline tumors/bifocal tumors - treat same as above For DI: the primary, infundibulum, and 3rd ventricle are all covered for initial phase and boost | anesthesia if needed for peds supine, face mask, CT sim, fuse with preop and postop MRI images | CR whole vent 21 Gy boost 9 Gy (=30 Gy total) PR or no chemo whole vent 24 Gy/ 1.5 boost 21 Gy/ 1.5 (=45 Gy total) | whole ventricle (lateral, third, fourth, suprasellar and pineal cisternas, plus pre-pontine cistern if 3rd ventriculostomy or large tumor), no extra CTV added COG whole ventricle atlas 0.3-0.5 cm PTV. Boost = pre-chemo GTV accounting for pushing borders plus + 0.5 cm margin CTV + 0.3-0.5 cm PTV. | carbo/etoposide x 4 cycles induction used by some with goal of reducing RT dose | 65% of germ cell tumors are germinomas. 15% of these produce low level beta-HCG If BHCG is >100, likely not germinoma | highly curable 80-100% CR and 90% 5yr OS | ACNS0232 (NCT00085098) ACNS1123, Murphy et al, ASTRO, 2018 MacDonald et al, COG whole ventricle atlas | |||||||||||||||||
36 | NGGCT (pediatric) | As above. Biopsy. Extent of resection does matter in NGGCT, but simple biopsy without debulking is still preferred due to morbidity from surgery | 6 cycles of alternating carbo/etoposide and ifosphamide/etoposide, or 6 cycles cis/etoposide If CR on MRI, treat with radiation. If no CR on MRI, do second look surgery. 36 Gy CSI + 18 Gy boost = 54 Gy. Use 1.8 Gy per fx. Boost spine mets to 45 Gy | see CSI section above | CSI 36 Gy IFRT boost to 54 Gy Spine mets boost 45 Gy | see Germinoma section | 6 cycles alternating carbo/etop and ifos/etop q 3 wk | NGGCT includes endodermal sinus tumor (high AFP), teratoma, embryonal carcinoma, choriocarcinoma (high beta-HCG) | DFS 70-80% long term ACNS0122 results 5-yr EFS 85% 5-yr OS 95% | ACNS0232 (NCT00085098) ACNS0122, Goldman et al, JCO, 2015 ACNS1123, Fangusaro et al, JCO, 2019 MacDonald et al, COG whole ventricle atlas | |||||||||||||||||
37 | Craniopharyngioma (pediatric) | CT/MRI shows calcified tumor with cystic components. Optho consult with full visual exam, endocrine consult Maximal safe resection or fenestration Prior, during, or shortly after surgery, give stress dose steroids in case ACTH response is blunted. May require vasopressin drip for DI (dismal prognosis) | Observation for GTR. For STR give 50.4-54 Gy SRS dose of 12 Gy can be done if small size and at least 1 mm from optics Also appropriate to observe after STR if small If <3 yo, delay RT until symptomatic | anesthesia if needed for peds supine, face mask, CT sim, fuse with preop and postop MRI images | IMRT 50.4-54 Gy SRS 12 Gy | GTV+0.5 CTV plus tailored PTV for potential cyst expansion Weekly imaging with MRI if feasible to assess cyst expansion | 10-yr OS 80-90% 85% LC if GTR, 25% if STR, 80% if STR+RT | endocrine abnormalities (diabetes insipidus most common but mainly due to surgery), neurocognitive changes, radiation necrosis, second malignancy, vascular occlusion (Moya Moya - strokes/sz), vasculitis, optic neuritis, dementia DI can be devastating and require lifelong DDAVP | Bishop et al, Craniopharyngioma. In Mahajan and Paulino, Radiation Oncology for Pediatric Brain Tumors. Greenfield et al, Radiother Oncol, 2015 Merchant et al, IJROBP, 2013 | ||||||||||||||||||
38 | Langerhans cell histiocytosis (pediatric) | H&P, bone skeletal survey, MRI brain. If pituitary location, workup for diabetes insipidus Curretage and steroids first RT typically only for pain palliation or, in some centers, for DI. If surgery is not an option, should respond to steroids or chemo. | Bony disease in peds: 6 Gy/3 or 10 Gy/5 Adults: 20 Gy/10 Various dose regimens exist DI: 1.5 x 8 = 12 Gy Non-bony disease may require higher dose | Peds 6 Gy/ 3 fx 10 Gy/ 5 fx Adults 20 Gy/ 10 fx DI 12 Gy/ 8 fx | 50% with pituitary stalk involved, have DI, proptosis, lytic bone lesions (Hand Schuller Christian) Pituitary location is also named Histiocytosis X | Ermoian et al, Pituitary tumors and Langerhans. In Mahajan and Paulino, Radiation Oncology for Pediatric Brain Tumors. Laird et al, IJROBP, 2018 Olschewski et al, Strahlenther Onkol, 2006 | |||||||||||||||||||||
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