What is the recommended chemoradiation protocol for nonmetastatic cancer?

Chemoradiation Protocol for Nonmetastatic Cancer

Cancer Type-Specific Protocols

The optimal chemoradiation protocol depends entirely on the primary cancer site, as treatment regimens vary substantially across different malignancies.

Small Cell Lung Cancer (Limited Stage)

For limited-stage SCLC, concurrent chemoradiation with cisplatin/etoposide starting with cycle 1 or 2 is the category 1 recommendation, using either 45 Gy in 1.5 Gy twice-daily fractions (preferred) or 60-70 Gy in 2.0 Gy once-daily fractions. 1

Chemotherapy regimen:

• Cisplatin 80 mg/m² day 1 + etoposide 120 mg/m² days 1-3 every 3 weeks for 4-6 cycles (preferred during concurrent RT) 1
• Alternative: Carboplatin AUC 5-6 day 1 + etoposide 100 mg/m² days 1-3 1

Radiation delivery:

• Twice-daily fractionation (1.5 Gy BID to 45 Gy total) provides superior survival compared to once-daily (median 23 vs 19 months; 5-year survival 26% vs 16%, P=0.04) but requires 6-hour interfraction interval 1
• Once-daily option: 2.0 Gy fractions to 60-70 Gy for patients unable to tolerate BID schedule 1
• Use 3D conformal techniques; IMRT may be considered in select patients 1

Critical constraints:

• Spinal cord: ≤41 Gy (BID) or ≤50 Gy (once-daily) 1
• Lung V20 <40% or mean lung dose ≤20 Gy 1
• Mean esophageal dose <34 Gy 1

Prophylactic cranial irradiation: 25 Gy in 10 fractions or 30 Gy in 15 fractions after completing chemotherapy for responders (category 1 recommendation) 1

Non-Small Cell Lung Cancer (Stage III)

Patients with stage III NSCLC should receive concurrent chemoradiation to 60 Gy in 2.0 Gy fractions with platinum-based chemotherapy. 1

Standard approach:

• Radiation: 60 Gy in 30 fractions (established by RTOG 7301 as superior to lower doses with 15% 3-year OS vs 10% at 50 Gy) 1
• Concurrent chemotherapy: Cisplatin-based regimens (weekly cisplatin or cisplatin/etoposide) 2, 3
• Do NOT escalate beyond 60 Gy: RTOG 0617 demonstrated inferior survival with 74 Gy vs 60 Gy (median OS 20.3 vs 28.7 months, HR 1.38, P=0.004) 1

Sequential chemoradiation option:

• For patients unable to tolerate concurrent therapy: 3 cycles platinum-based chemotherapy followed by 60 Gy radiation 1
• Sequential approach shows improved survival vs radiation alone (median 13.7 vs 9.6 months, P=0.012) 1

Accelerated fractionation alternative:

• 66 Gy in 24 daily fractions for patients unsuitable for concurrent therapy 1

Head and Neck Cancer (Locally Advanced)

For locally advanced head and neck cancers, deliver 70 Gy in 2.0 Gy fractions to primary tumor and gross adenopathy with concurrent cisplatin 100 mg/m² every 3 weeks for 3 doses. 1, 4, 5

Radiation volumes:

• Primary tumor and gross adenopathy: 70 Gy 1, 5
• Uninvolved nodal stations: 44-64 Gy 1
• IMRT is preferred to minimize dose to salivary glands and critical structures 5

Chemotherapy options:

• Concurrent cisplatin 100 mg/m² every 3 weeks (standard) 1, 4
• Alternative: Weekly cisplatin 40 mg/m² (cumulative 160-200 mg/m² target) 4

Induction approach (for organ preservation):

• TPF regimen: Docetaxel 60-75 mg/m², cisplatin 60-75 mg/m², 5-FU 600-750 mg/m² continuous infusion × 5 days every 3 weeks for 3 cycles 4
• Follow with consolidation chemoradiation within 21-28 days 4

Postoperative setting:

• For extracapsular extension and/or positive margins: 60-66 Gy with concurrent cisplatin 100 mg/m² every 3 weeks 1, 5
• Complete within 6 weeks of surgery 5

Anal Cancer (Nonmetastatic)

Concurrent chemoradiation with mitomycin/5-FU or mitomycin/capecitabine is the standard primary treatment for nonmetastatic anal canal cancer. 1

Chemotherapy regimens:

• Mitomycin + 5-FU: 5-FU as 96-120 hour infusion weeks 1 and 5; mitomycin bolus day 1 or 2 1
• Mitomycin + capecitabine: Capecitabine 825 mg/m² PO BID Monday-Friday during RT for 4-6 weeks; mitomycin bolus 1
• Alternative (category 2B): 5-FU/cisplatin 1

Radiation delivery:

• Standard dose and fractionation not explicitly detailed in provided evidence
• Use normal tissue-sparing techniques 1

Rectal Cancer (Locally Advanced)

For locally advanced rectal cancer, deliver 45.0-50.4 Gy in 1.8-2.0 Gy fractions to the pelvis with concurrent capecitabine or 5-FU, followed by a 4-6 Gy boost to the primary tumor. 6

Chemotherapy options:

• Capecitabine 825 mg/m² PO BID, 5 days/week during RT (non-inferior to 5-FU with favorable toxicity) 6
• 5-FU continuous infusion 225 mg/m²/day during RT 6

Radiation volumes:

• Primary tumor with 2-5 cm margin, entire mesorectum, presacral nodes, internal iliac nodes, obturator nodes 6
• Boost: Additional 4-6 Gy in 2-4 fractions after 45 Gy 6

Short-course alternative:

• 25 Gy in 5 fractions followed by surgery within 1 week for T3 tumors without sphincter preservation needs 6

Technical requirements:

• Use 3D-CRT, VMAT, or IMRT 6
• Small bowel V15 <120 mL, abdominal cavity V45 <195 mL 6

Bladder Cancer (Muscle-Invasive)

For bladder preservation in muscle-invasive bladder cancer, perform maximal TURBT followed by 60-66 Gy with concurrent cisplatin-based chemotherapy or 5-FU/mitomycin. 1

Chemotherapy regimens:

• Cisplatin + 5-FU (preferred doublet) 1
• Cisplatin + paclitaxel 1
• 5-FU + mitomycin C 1
• Cisplatin alone or low-dose gemcitabine (category 2B alternatives) 1

Radiation approach:

• After complete TURBT: 60-66 Gy external beam RT 1
• Two doses concurrent chemotherapy weeks 1 and 4 1
• Alternative: Induction 40-45 Gy, reassess at 3 weeks, complete to 66 Gy if no residual disease 1

For poor performance status/non-cystectomy candidates:

• Concurrent chemoRT with cisplatin or 5-FU/mitomycin preferred over RT alone 1

Common Pitfalls and Caveats

Timing considerations:

• For SCLC, start RT with cycle 1 or 2 of chemotherapy (not after completion) 1
• For head and neck postoperative cases, complete RT within 6 weeks of surgery 5
• For head and neck with induction, begin consolidation within 21-28 days of last induction cycle 4

Performance status requirements:

• Twice-daily RT for SCLC requires excellent PS and good pulmonary function 1
• Concurrent chemoRT carries high toxicity burden; sequential approach for PS 2 or significant comorbidities 1

Dose escalation errors:

• Do NOT exceed 60 Gy for stage III NSCLC based on RTOG 0617 showing harm with 74 Gy 1
• Do NOT add oxaliplatin to rectal cancer chemoRT (no benefit, increased toxicity) 6

Technical requirements:

• Use 3D conformal or IMRT techniques, not 2D planning 1, 6, 5
• Respect normal tissue constraints strictly to minimize toxicity 1, 6
• For SCLC BID fractionation, maintain ≥6 hour interfraction interval 1