When is radiotherapy indicated for adult patients with solid tumors, and what are the typical curative dose regimens, planning requirements, acute and late toxicities, and alternative treatment options?

Radiotherapy for Adult Solid Tumors

Radiotherapy is indicated for approximately 50-65% of all adult cancer patients with solid tumors, either as definitive treatment for unresectable disease, as adjuvant therapy following surgery to reduce local recurrence, or for palliation of symptoms, with standard curative doses typically ranging from 60-70 Gy delivered in 1.8-2 Gy fractions. 1, 2, 3

Primary Indications for Radiotherapy

Definitive (Curative Intent) Radiotherapy

Definitive radiotherapy at curative doses (approximately 66-70 Gy) should be offered when:

• Surgical resection would cause unacceptable morbidity or poor functional outcomes 4
• The tumor is deemed unresectable due to location, local invasion, or extent of disease 4
• Medical comorbidities preclude safe surgical intervention 4

For soft tissue sarcomas specifically, definitive radiotherapy at 66 Gy in 33 fractions over 6.5 weeks is recommended when surgery is not feasible, with outcomes directly related to tumor size, grade, and radiation dose delivered 4.

For salivary gland malignancies, definitive radiotherapy to approximately 70 Gy (or equivalent) provides local control benefits and cause-specific survival of approximately 40% at 10 years in unresectable cases 4.

Adjuvant (Post-Operative) Radiotherapy

Post-operative radiotherapy is indicated to reduce local recurrence rates in:

• Soft tissue sarcomas: 60-66 Gy in 1.8-2 Gy fractions following surgical resection 4
• Brain metastases: Stereotactic radiosurgery (SRS) after open surgical resection of solitary brain metastasis decreases local recurrence 4
• Salivary gland malignancies: Routine post-operative radiotherapy to tumor bed and nodes at 65 Gy with standard fractionation 4

Critical caveat: Post-operative boost radiotherapy for positive resection margins in soft tissue sarcomas is not recommended, as it is unlikely to be beneficial and may result in excess late toxicity 4.

Pre-Operative (Neo-Adjuvant) Radiotherapy

Pre-operative radiotherapy at 50-50.4 Gy in 1.8-2 Gy fractions is preferred when:

• Reducing late radiation toxicity is a priority (smaller treatment volumes possible with tumor in situ) 4
• The tumor is borderline operable and radiotherapy might render it resectable 4
• The tumor is particularly radiosensitive (e.g., myxoid liposarcoma) where significant shrinkage facilitates surgery 4

Surgery timing is typically 4-8 weeks after completion of pre-operative radiotherapy 4. Short-course hypofractionated schedules (25-30 Gy in 5 fractions over one week) achieve equivalent local control without increased toxicity 4.

Stereotactic Radiosurgery (SRS) for Brain Metastases

SRS is recommended as:

• An alternative to surgical resection for solitary metastases when surgery would induce new neurological deficits and tumor volume/location are not likely to cause radiation-induced injury 4
• Primary treatment for 1-4 brain metastases with cumulative volume <7 mL, instead of whole brain radiotherapy 4
• Treatment for >4 brain metastases with cumulative volume <7 mL to improve median overall survival 4

Standard Curative Dose Regimens

Conventional Fractionation

• Standard curative dose: 60-66 Gy in 1.8-2 Gy fractions, 5 fractions per week 4
• Glioblastoma (IDH-wild-type): 60 Gy in 1.8-2 Gy fractions with concurrent and adjuvant temozolomide 4, 5
• IDH-mutant gliomas (WHO grade 2-3): 50-60 Gy in 1.8-2 Gy fractions 4
• Non-small cell lung cancer (locally advanced): Minimum 60 Gy with classical fractionation 4

No evidence supports doses >60 Gy for higher WHO grade gliomas 4.

Hypofractionated Regimens

Hypofractionated radiotherapy is appropriate for:

• Elderly patients (>65-70 years) or poor performance status: 40 Gy in 15 fractions (2.67 Gy per fraction) 4
• Patients with <3 months life expectancy: Provides better quality of life 4
• Pre-operative soft tissue sarcoma: 25-30 Gy in 5 fractions over one week 4

Critical warning: Further hypofractionation to 5×5 Gy may cause neurocognitive adverse events if patients live longer due to improved systemic treatment 4.

Planning Requirements

Target Volume Delineation

Gross Tumor Volume (GTV):

• Macroscopic visible disease on pre- and post-contrast T1-weighted MRI sequences 4
• For post-operative cases: residual disease plus postoperative tumor bed 4

Clinical Target Volume (CTV):

• GTV plus 1.0-2.0 cm margin for microscopic invasion 4
• Modified to include T2-weighted or FLAIR signal abnormalities (edema) 4
• Constrained to anatomical barriers (ventricles, tentorium, falx) 4

Planning Target Volume (PTV):

• CTV plus 0.3-0.5 cm margin for setup uncertainties 4

Technical Requirements

• CT slice thickness: ≤0.5 cm for planning scans 4
• Photon energy: 4-6 MV linear accelerator megavoltage for most applications 4
• High-energy photons: ≥9 MV with individualized lead shielding and computerized dosimetry 4
• Dose Volume Histograms (DVHs): Should be constructed for PTVs and organs at risk 4
• Conformal delivery: Individually shaped, conformal fixed beams using beam's-eye-view facility 4

Organs at Risk

Structures requiring delineation and dose constraints:

• Optic nerves, optic chiasm, retinae, lenses 4
• Brainstem, pituitary, cochleae, hippocampi 4
• Spinal cord and major vessels 4

Acute Toxicities

Common Acute Effects (During or Within 3 Months of Treatment)

• Wound healing complications: Higher incidence with pre-operative radiotherapy for soft tissue sarcomas 4
• Acute respiratory distress syndrome (ARDS): Increased risk after pneumonectomy following induction chemoradiotherapy for lung cancer 4
• Gastrointestinal toxicity: Significant with weekly cisplatin combined with split-course radiotherapy 4
• Radiation dermatitis and mucositis: Common in head and neck radiotherapy 4
• Fatigue and localized pain: Universal across treatment sites 2, 6

Management priority: Pre-operative radiotherapy may not be suitable for patients or tumor locations where wound healing is anticipated to be problematic 4.

Late Toxicities

Long-Term Effects (>3 Months Post-Treatment)

• Radiation necrosis: Risk increases with higher doses and larger volumes, particularly near critical structures 4
• Neurocognitive decline: Especially with whole brain radiotherapy or high-dose focal treatment 4
• Fibrosis and tissue contracture: Common in soft tissue sarcoma treatment 4
• Secondary malignancies: Long-term risk, particularly in younger patients 7
• Vascular complications: Carotid stenosis, stroke risk in head and neck radiotherapy 4

Critical consideration: Modern highly conformal techniques (IMRT, proton therapy) provide superior target coverage and sparing of non-malignant tissue, potentially reducing late toxicity 4.

Alternative Treatment Options

When Radiotherapy Should Be Avoided or Modified

Surgical resection remains preferred when:

• Complete resection is achievable without significant morbidity 4
• The tumor is in a favorable location for safe removal 4
• Patient has good performance status and life expectancy 4

Systemic therapy alternatives:

• Chemotherapy alone: For chemosensitive tumors or when local control is not the primary goal 4, 2
• Targeted therapy: For tumors with actionable mutations (e.g., BRAF V600 in melanoma) 8
• Immune checkpoint inhibitors: Anti-PD-1/PD-L1, anti-CTLA-4 for immunogenic tumors 8

Observation ("wait-and-see"):

• Appropriate for select IDH-mutant, 1p/19q-codeleted oligodendrogliomas WHO grade 2 4
• Low-grade, asymptomatic tumors in elderly patients with limited life expectancy 4

Palliative Radiotherapy Regimens

For symptom control in metastatic or advanced disease:

• 8 Gy single fraction 4
• 20 Gy in 5 fractions over 1 week 4
• 30 Gy in 10 fractions over 2 weeks 4
• 36-40 Gy in 12-15 fractions over 2.5-3 weeks 4

Dose-fractionation is selected on an individual patient basis based on symptoms, performance status, and prognosis 4.

Common Pitfalls and How to Avoid Them

Critical Errors to Prevent

1. Delaying radiotherapy start: Should begin within 3-5 weeks after surgery 4

2. Inadequate target volume coverage: Always include dural tail and abnormal bone for meningiomas 4; include perineural tracts for salivary gland malignancies with perineural spread 4

3. Omitting MGMT testing in glioblastoma: MGMT promoter methylation predicts temozolomide benefit, though treatment is recommended regardless of status for standard-risk patients 4, 5

4. Using whole brain radiotherapy for limited brain metastases: SRS provides superior outcomes for 1-4 metastases with cumulative volume <7 mL 4

5. Adding post-operative boost for positive margins in sarcoma: Unlikely to benefit and increases late toxicity 4

6. Inadequate quality assurance: Modern radiotherapy requires rigorous QA programs to ensure geometric accuracy and dose delivery 3, 7