Small Cell Lung Cancer and Bronchial neuroendocrine tumor

Question 1

Small cell lung cancer (SCLC) accounts for what % of new lung cancer Dx in the United States? What % of lung cancer deaths?

Answer 1

14% (31,000 cases/yr) of new lung cancer diagnosed in 2017 is SCLC, accounting for ∼25% of lung cancer deaths annually.

Question 2

What % of SCLC is linked to smoking?

Answer 2

Nearly all cases of SCLC are linked to smoking.

Question 3

What is the median age of Dx of SCLC? What % of pts are >70 yo at Dx?

Answer 3

The median age of SCLC Dx is 64 yrs, with 25% of pts presenting at age >70 yrs.

Question 4

What % of pts with SCLC presents with metastatic Dz?

Answer 4

67% of SCLC pts present with mets, most commonly to the contralat lung, contralat or bilat malignant pleural effusion, liver, renal, adrenals, bone, BM, and brain.

Question 5

What are the pathologic characteristics of SCLC?

Answer 5

Small round blue cells of epithelial origin with neuroendocrine differentiation, ↑ mitotic count, and ↑ N/C ratio

Question 6

What are the markers that characterize SCLC?

Answer 6

Markers that characterize SCLC include S100, synaptophysin+, chromogranin+, and neurotensin + EGFR–.

Question 7

What pathology finding is often associated with SCLC?

Answer 7

Crush artifact

Question 8

What are some common neurologic and endocrine paraneoplastic syndromes associated with SCLC?

Answer 8

Neurologic: Lambert–Eaton syndrome (antibody to presynaptic voltage-gated calcium channels), encephalomyelitis, sensory neuropathy (anti-Hu antibody)
Endocrine: Cushing Dz (↑↑ ACTH), SIADH (↑↑ ADH)

Question 9

What is the most common chromosomal abnormality associated with SCLC but not seen with extrapulmonary small cell carcinomas?

Answer 9

Deletion of 3p (95% of cases, particularly 3p14–25 region, with inactivation of at least 3 tumor suppressor genes, including FHIT and RASSF1A)

Question 10

What is the most common genetic alteration seen in SCLC?

Answer 10

Amplification of the bcl-2/C-myc family of oncogenes is most common but likely is not the initiating event. Other common abnormalities include loss of p16, loss of Rb, and mutation in p53.

Question 11

How do pts with SCLC usually present?

Answer 11

Large hilar mass with bulky mediastinal LAD that causes cough, shortness of breath, weight loss, postobstructive pneumonia, and debility. Other common presentations include paraneoplastic syndromes such as Lambert–Eaton, SIADH, or ectopic ACTH production.

Question 12

Classically, does SCLC present centrally or peripherally in the lung?

Answer 12

Classically, SCLC presents centrally in the lung.

Question 13

What histology is most commonly associated with superior vena cava obstruction (SVCO) syndrome?

Answer 13

SCLC is most commonly associated with SVCO syndrome.

Question 14

Do SCLC pts present with solitary peripheral nodules without mediastinal LAD? What % have true stage I dz (T1–2, N0) after mediastinal staging?

Answer 14

This presentation is very uncommon; <5% of pts have true stage I dz.

Question 15

How should pts be managed whose FNA results cannot clearly differentiate b/w small cell and atypical carcinoid histology?

Answer 15

Surgical staging, with mediastinoscopy → surgical resection if the MNs are negative (NCCN 2018)

Question 16

Once SCLC has been diagnosed in a pt who presents with a large hilar mass, what further workup is necessary besides the basic H&P and labs?

Answer 16

LDH levels, CT C/A/P +/– PET, MRI brain, bone scan if PET is not done, BM Bx (for pts with elevated LDH), thoracentesis with cytopathologic exam for pts with pleural effusion, and smoking cessation counseling

Question 17

What % of pts with SCLC at the time of Dx present with brain mets, BM involvement, and bone mets?

Answer 17

Brain mets: 10%–15% (30% are asymptomatic)
BM involvement: 5%–10%
Bone mets: 30%

Question 18

What is the latest AJCC system for staging SCLC?

Answer 18

The same as for non-SCLC, but this system is not commonly used.

Question 19

How SCLC is most commonly staged?

Answer 19

SCLC is commonly staged using the International Association of Lung Cancer system, which is a modification of the VALCSG system. There are 2
stages: limited and extensive. Tumors are staged according to whether the Dz can be encompassed within an RT port. Limited stage Dz is typically
confined to the ipsi hemithorax, without malignant pleural effusion, contralat Dz, or mets; other presentations are usually extensive stage.

Question 20

What % of pts present with limited-stage SCLC (LS-SCLC)?

Answer 20

∼33% of pts present with LS-SCLC.

Question 21

What are the most important adverse prognostic factors in SCLC? What additional factors are assoc. w/ poor prognosis in extensive- and limited stage
dz?

Answer 21

Poor PS; extensive-stage; weight loss (>5% in prior 6 mos); ↑ LDH; male gender; endocrine paraneoplastic syndromes (controversial), variant, or of mixed cell type; metastatic Dz. For extensive-stage: older age, poor PS, abnl Cr/LDH, >1 metastatic site. For limited-stage: male, age >70, abnl LDH,
>stage I.

Question 22

What is the MS of untreated limited- and extensive-stage SCLC?

Answer 22

∼12 wks for limited stage and ∼6 wks for extensive stage, based on a VALCSG trial comparing cyclophosphamide to placebo.

Question 23

What is the MS for pts with limited- vs. extensive-stage SCLC?

Answer 23

Limited stage: 20–30 mos

Extensive stage: 8–13 mos

Question 24

What is the long-term survival rate in limited-stage SCLC treated with a combined modality?

Answer 24

26% long-term survival (5 yrs) (Turrisi A et al., NEJM 1999)

Question 25

What additional workup should be considered for pts with carcinoid tumors of the lung?

Answer 25

Consider octreotide scan.

Question 26

What is the Tx paradigm for pts with LS-SCLC?

Answer 26

LS-SCLC Tx paradigm: 4 cycles of EP chemo (etoposide [120 mg/m2, days 1–3] + cisplatin [60 mg/m2, day 1, q3wks]) + concurrent RT (only 1 cycle is concurrent). Current standard RT regimen is based on INT-0096: 45 Gy in 1.5 Gy bid × 30 fx.

Question 27

What is the Tx paradigm for pts with T1–2N0M0 SCLC?

Answer 27

Lobectomy with mediastinal dissection and adj full course chemo. (NCCN 2018) This situation is seen in ∼5% of SCLC cases. The importance of adj chemo and PCI after complete resection for early-stage SCLC was highlighted in an NCDB analysis (Yang G et al., JCO 2016). If there are nodal involvement, consideration is made for adj mediastinal RT concurrent with chemo. PCI is also recommended. For more advanced lesions, 2 randomized studies (LCSG 832 [Lad T, Chest 1994] and the MRC [Fox W et al., Lancet 1973]) showed no benefit to Sg over definitive RT. For medically inoperable pts, consideration can be made for SBRT +consolidation full course chemo and PCI. Mediastinal staging with EBUS should be made prior to SBRT. This is based on a multicenter case series and NCDB analysis, demonstrating comparable outcomes as surgical series. (Verma V et al., IJROBP 2017; Stahl et al., Lung Cancer 2017)

Question 28

What is the OS and LC benefit of adding RT to chemo in LS-SCLC?

Answer 28

There is an OS benefit of 5% based on Pignon J-P et al. meta-analysis (NEJM 1992), with LC benefit of 25%–30%. (Warde P et al., NEJM 1992 [meta-analysis])

Question 29

What is the benefit of smoking cessation prior to Tx in pts with limited stage SCLC?

Answer 29

↓ Toxicity and ↑ survival, based on a retrospective review (Videtic GMM et al., IJROBP 2003)

Question 30

What are the typical response rates seen after concurrent CRT for LS-SCLC?

Answer 30

Typical response rates are 80%–95% with CR rates of 40%–60%.

Question 31

What is the median duration of response for pts with LS-SCLC after definitive Tx?

Answer 31

6–8 mos is the median duration of response.

Question 32

What is the preferred Tx approach for elderly pts (age >70 yrs) with LS-SCLC?

Answer 32

Depends on PS. In pts with good PS, combined CRT is preferred; they were shown to have 16% absolute 3-yr OS benefit with addition of RT to chemo (Corso CD et al., JCO 2015). Otherwise, standard combination chemo is better than single-agent cytotoxic agents.

Question 33

What is the MS of SCLC pts after recurrence if treated with salvage chemo?

Answer 33

4–5 mos is the MS for these pts.

Question 34

Why is EP the preferred regimen in concurrent CRT for LS-SCLC?

Answer 34

EP causes little mucosal toxicity, offers low risk of interstitial pneumonitis, and has lower cardiac toxicity compared to doxorubicin.Full systemic doses can be administered with RT, and there is modest hematologic toxicity. EP has a better therapeutic ratio over the older regimen of CAV (cyclophosphamide, doxorubicin, and vincristine), but it confers no survival benefit.

Question 35

What are the benefits and disadvantages of substituting carboplatin for cisplatin in EP for Tx of SCLC? Is there a difference in efficacy?

Answer 35

Carboplatin is less emetic, neuropathic, nephropathic, ototoxic, but there is more heme toxicity. A meta-analysis found no difference b/w cisplatin vs. carboplatin regimens. (Rossi A et al., JCO 2012)

Question 36

Is there a benefit to maintenance chemo after the initial 4–6 cycles in the Tx of SCLC?

Answer 36

No. Maintenance chemo only produces minor prolongation of response without improving survival and increasing cumulative toxicity.

Question 37

Is there a benefit of irinotecan compared to etoposide when added to cisplatin in the Tx of SCLC?

Answer 37

No. A Japanese RCT demonstrated a survival benefit with irinotecan, but this was not reproduced in 3 larger trials conducted outside Japan. However, a phase III trial found slightly improved OS with irinotecan over oral etoposide with carboplatin (Hermes A et al., JCO 2008), so irinotecan + carboplatin is an option. (NCCN 2018)

Question 38

What is the optimal sequence of combining chemo with RT?

Answer 38

Concurrent is better than sequential (JCOG: Takada M et al., JCO 2002): MS 27 mos vs. 20 mos; 5-yr OS 30% vs. 20% (10% OS benefit)

Question 39

What evidence supports early concurrent CRT over late RT with induction CT → CRT?

Answer 39

``` NCIC data (Murray N et al., JCO 1993): phase III, 308 pts. 5-yr OS was 20% (early RT) vs. 11% (late RT). Yugoslavia data (Jeremic B et al., JCO 1997): an early vs. late RT trial showed better MS (34 mos vs. 26 mos) and 5-yr OS (30% vs. 15%) for early. Meta-analysis of 7 trials (Fried DB et al., JCO 2004): early (<9 wks) vs. late (>9 wks) after chemo. There was 5.2% better 2-yr OS with early RT. ```

Question 40

What is the recommended RT dose in CRT for LS-SCLC?

Answer 40

45 Gy in 1.5 Gy BID or 60–70 Gy in 2 Gy QD (NCCN 2018) CONVERT (European phase III trial) comparing 66 Gy/2.0 Gy QD vs. standard 45 Gy/1.5 Gy BID showed similar OS and toxicity (Faivre-Finn Cet al., Lancet Oncol 2017) CALGB 30610 is currently testing 70 Gy/2.0 Gy QD vs. standard 45 Gy/1.5 Gy BID. Previous RTOG 0712 regimen of 61.2 Gy in 5 wks (1.8 Gy qd × 16 fx → BID) was d/c in CALGB trial although it was not more toxic than the 7-wk regimen.

Question 41

What randomized trial demonstrated a clear superiority of altered fractionation with chemo compared to qd RT in the Tx of SCLC?

Answer 41

INT-0096 (Turrisi AT et al., NEJM 1999): phase III, 381 pts, EP × 4 cycles + RT at 1st cycle; randomization with 1.5 Gy bid × 3 wks vs. 1.8 Gy qd × 5 wks (both to 45 Gy); all rcvd prophylactic cranial irradiation (PCI) to 25 Gy. There was better 5-yr OS (26% vs. 16%) and LC (64% vs. 48%) in the bid arm. There was increased grade 3 esophagitis (27% vs. 11%) in the bid regimen, but not in the grade 4 toxicity. Criticism: 45 Gy qd is not biologically equivalent to the accelerated hyperfx of 45 Gy in 30 fx.

Question 42

Do any studies support dose escalation with conventional fractionation rather than traditional bid approach?

Answer 42

CALGB 8837 (Choi H et al., JCO 1998): phase I MTD in 50 pts of 2 RT regimens: 1.5 Gy/fx bid or 2.0 Gy/fx qd; MTD of bid was 45 Gy, whereas MTD of qd regimen was >70 Gy. Updated survival results were that 6-yr OS was better in the qd regimen compared with bid (36% vs. 20%). CALGB 30610 is an ongoing phase III trial comparing 45 Gy in 3 wks (arm A: INT-0096) vs. 70 Gy in 35 fx (arm B: CALGB regimen). (Arm C, 61.2 Gy in 5 wks (1.8 Gy qd × 16 fx → bid, as in RTOG 97–12, was dropped.)

Question 43

Describe classic RT targets for LS-SCLC?

Answer 43

Gross tumor, ipsi hilum, bilat MN from T inlet (1st rib) down to 5 cm below the carina. CTV = GTV + 1.5 cm (and elective hilum and MN regions + 8mm), PTV = CTV + 1 cm.

Question 44

What T RT field arrangements are classically used for treating LS-SCLC?

Answer 44

Minimize contralat lung exposure with AP/PA to 15 Gy (1.5 Gy bid × 5 days) with oblique field to 45 Gy (AP/PA in AM and obliques for PM sessions).

Question 45

Should elective nodal irradiation be performed?

Answer 45

Historically, clinically uninvolved MNs were included. However, several modern studies showed that omission of ENI results in very low rates of isolated nodal recurrences of <5% if PET staging used. The CALGB 30610 and CONVERT trials have omitted ENI.

Question 46

Should you cover the pre- or postinduction systemic therapy Dz for the tumor and nodal volumes?

Answer 46

In pts who have systemic therapy before RT, the tumor GTV can be limited to the postchemo volume, based on 2 trials comparing pre- vs. postchemo volumes (Kies MS et al., JCO 1987; Hu X et al., Cancer 2011). The nodal GTV should include prechemo involved nodes but does not need to cover the entire extent of prechemo Dz.

Question 47

Are there circumstances where IMRT may be beneficial?

Answer 47

Consider IMRT if V20 >30% or FEV1 <1 L.

Question 48

What PTV margins should be used with/without 4D-CT simulation?

Answer 48

PTV is CTV + 0.5 cm if daily setup imaging is used and if ITV assessment is done during simulation and the planning process (either breath-hold or 4DCT imaging). If a free-breathing non-ITV approach is used (non–4D-CT simulation), the PTV is CTV + 1.5 cm (sup–inf direction) and 1.0 cm in the axial direction. If a breath-holding non-ITV, PTV is CTV + 1.0 cm (sup–inf direction) and 0.5 cm in the axial direction.

Question 49

Is IMRT associated with worse outcomes compared to 3D-CRT?

Answer 49

Retrospective review of MDACC experience demonstrated no difference in LC or OS when IMRT was compared to 3D-CRT. PEG tube placement was significantly lower in IMRT cohort. (Shirvani SM et al., Int J Radiat Oncol Biol Phys 2013)

Question 50

What is the role of PCI in LS-SCLC? Is there an OS benefit with it?

Answer 50

Auperin meta-analysis of 7 RCTs (NEJM 1999) compared PCI vs. no PCI after CR following induction chemo +/– RT and no evidence of brain mets before randomization. There was ↓ 3-yr incidence of brain mets (33% vs. 59%) and 5.4% better 3-yr OS (20.7% vs. 15.3%) and improved DFS. There was a trend to a better outcome with ↑ doses and RT <4 mos from the start of chemo.

Question 51

What PCI dose is now standard for LS-SCLC?

Answer 51

25 Gy in 10 fx is now the standard dose for PCI for LS-SCLC. (RTOG 0212-Intergroup: Le Pechoux C et al., Lancet Oncol 2009)

Question 52

For pts with LS-SCLC what PCI doses were compared in RTOG 0212?

Answer 52

``` Standard doses (25 Gy in 10 fx) vs. higher doses (36 Gy in either 18 fx qd or 24 fx bid). There was no difference in the 2-yr incidence of brain mets, but there was an OS and chest relapse advantage for the standard arm (42% vs. 37%, p = 0.05) d/t greater cancer-related mortality in the high-dose group. There was higher 1-yr chronic neurotoxicity in the higher-dose arm (∼85%–90% vs. 60%). (Le Pechoux C et al., Lancet Oncol 2009; Wolfson AH et al., IJROBP 2011) ```

Question 53

What is the effect of PCI timing after the initiation of chemo for SCLC?

Answer 53

Based on Auperin meta-analysis, there was a ↓ in risk of brain mets with earlier PCI (<4–6 mos vs. >6 mos) without an effect on risk of death.

Question 54

Are there data demonstrating greater neuropsychologic complications after PCI for SCLC?

Answer 54

No. The data actually demonstrate no difference with or without PCI in a randomized trial addressing the question of neuropsychologic changes after PCI (Arrigada et al., JNCI 1995). Most pts (97%) actually have abnl neuropsychologic testing after chemo and before PCI, without a difference after PCI. (Komaki R et al., IJROBP 1995)

Question 55

What is the recommended adj Tx for SCLC if the MNs are found to be involved after attempted surgical resection?

Answer 55

Concurrent CRT directed at the MN (per NCCN 2018); if node–, adj chemo alone

Question 56

What is the Tx paradigm for pts with extensive-stage SCLC?

Answer 56

Extensive-stage SCLC Tx paradigm: multiagent chemo regimen including EP. Consider consolidation RT to the thorax for pts who achieve a CR to distant Dz after initial chemo (Jeremic B et al., JCO 1999). Also, PCI found to offer survival benefit even if extensive-stage Dz. (Slotman B et al., NEJM 2007)

Question 57

How many cycles of chemo should be given for extensive-stage SCLC?

Answer 57

4–6. Giving >4–6 cycles only modestly prolongs response duration and does not improve survival, while increasing cumulative toxicity.

Question 58

What additional chemo agents, when added to EP, have been shown to modestly improve the survival of pts with extensive-stage SCLC?

Answer 58

Ifosfamide or cyclophosphamide + an anthracycline have been shown to modestly improve survival.

Question 59

Is there evidence to support consolidative RT to T Dz in extensive-stage SCLC?

Answer 59

Yes. 2 RCTs supported this. A European multicenter trial (Slotman et al., Lancet 2015) randomized 498 extensive-stage SCLC pts who had any response to 4–6 cycles of platinumbased chemo (70% had PR) to T RT (30 Gy in 10 fx) + PCI or PCI alone. The primary endpoint, 1-yr OS, was not significantly improved (p = 0.07), but the 2-yr OS was improved in those receiving T RT (2-yr OS 13% vs.3%, p = 0.004). There was a 50% reduction in intrathoracic recurrences, improved 6-mo PFS, but no difference in progression at any site. T RT was well tolerated with no severe toxicity. The benefit of consolidation T RT was mostly limited to the pts who had residual Dz after systemic therapy. Jeremic et al. (JCO 1999) enrolled 210 extensive-stage pts. All rcvd EP × 3. The subset of 109 pts who achieved a CR at all distant sites was randomized to rcv consolidative RT (accelerated hyperfx to 54 Gy) with concurrent carboplatin/etoposide or not. In both arms, pts rcvd PCI and consolidative EP. Consolidative CRT improved 5-yr OS (9.1% vs. 3.7%) and MS (17 mos vs. 11 mos). There was a trend in favor of LC but not DM-free survival.

Question 60

What are some salvage chemo agents used at the time of recurrence for SCLC?

Answer 60

Oral topoisomerase I inhibitors are standard for postchemo failure. (Topotecan was tested in RCTs showing doubling of survival [26 wks vs. 14 wks] compared with supportive care; irinotecan as a single agent was not tested.) Paclitaxel, docetaxel, TMZ, nivolumab +/– ipilimumab, vinorelbine, oral etoposide, gemcitabine, and CAV are some others.

Question 61

What seminal study demonstrated a survival benefit with PCI in pts with extensive-stage SCLC with any response to chemo? What are some main criticisms of this study?

Answer 61

EORTC 08993 RCT (Slotman BJ et al., NEJM 2007): 286 pts with extensive-stage SCLC treated with chemo; primary endpoint was time to symptomatic brain mets; pts randomized to +/– PCI after any response to chemo; most PCI pts given 20 Gy in 5 fx. PCI lowered the risk of symptomatic mets and improved DFS and OS (5.4 mos –PCI vs. 6.7 mos+PCI). 1-yr OS nearly doubled (13% –PCI vs. 27% +PCI). Criticisms: Pre-Tx brain imaging is not required. The RT group was more likely to rcv chemo at the time of extracranial progression (68% vs. 45%). Only about half (59%) of pts in the control group rcvd WBRT for intracranial progression of Dz.

Question 62

Is there a benefit of PCI for extensive-stage pts who have a (negative) staging brain MRI?

Answer 62

Controversial, but likely not. Although the EORTC 08993 trial showed OS benefit with PCI for extensive-stage SCLC, the trial did not require pre-Tx brain imaging. The Japanese phase III randomized trial of PCI vs. no PCI in extensive-stage SCLC pts who had a negative staging brain MRI, closed early d/t futility of PCI after 163 pts were enrolled. There was no improvement of OS for PCI vs. no PCI; in fact, there was a trend toward a negative impact on median OS. (10.1 mos [PCI] vs. 15.1 mos [no PCI], p =0.09). (Takahashi T et al., Lancet Oncol 2017)

Question 63

What was the greatest QOL alteration after PCI in the EORTC trial for extensive-stage SCLC?

Answer 63

3-mo QOL assessment showed that the largest negative impact of PCI was fatigue and hair loss. Worsening role, emotional, and cognitive function were also seen after PCI. (Slotman BJ et al., JCO 2009)

Question 64

What PCI dose should be given for extensive-stage SCLC?

Answer 64

The preferred dose is still 25 Gy in 10 fx, similar to LS-SCLC, however a shorter course (e.g., (20 Gy in 5 fx) can be considered for selected pts, such as those with less than a CR (most pts rcvd 20 Gy in 5 fx in the Slotman trial)).

Question 65

What is the current recommendation for PCI in pts with SCLC?

Answer 65

Indicated for limited stage and considered for extensive stage (NCCN 2018), CR/PR after chemo +/– consolidation RT, +/– MRI brain, PS of ECOG 0–2, within 3–6 wks of last cycle of chemo, 25 Gy in 10 fx. Also rcvd for pts who have had a complete resection. In pts with less than a CR, PCI is at the discretion of the treating physician.

Question 66

How do you treat SCLC pts who present with a limited number brain mets?

Answer 66

Whole brain radiotherapy (30 Gy in 10 fx). SRS should not be offered outside a clinical trial since these pts tend to develop multiple CNS mets, although may be considered if pts have rcvd prior PCI in selected pts. (NCCN 2018)

Question 67

In SCLC pts with SVCO, cord compression, or brain mets, what regimen is preferred as upfront palliative Tx: RT or chemo?

Answer 67

In a chemonaive pt presenting with SVCO, RCTs have shown a similar symptomatic response rate with chemo compared with RT. But in a chemorefractory pt, RT is the preferred regimen. In pts with cord compression/brain mets, RT is standard (in both chemonaive and chemorefractory pts).

Question 68

How is palliative RT delivered for SVCO syndrome in pts with SCLC?

Answer 68

Generally, a few large fx upfront (3–4 Gy × 2–3) → more definitive dosing in conventional fractionation (qd or bid regimen)

Question 69

What fractionation scheme is optimal for pts with lung cancers treated with palliative RT for Sx such as hemoptysis, cough, pain, and shortness of breath?

Answer 69

Conventional is probably no better than hypofractionation. In a Norwegian RCT, Sundstrom et al. tested 30 Gy in 10 fx vs. 17 Gy in 2 fx (1 wk apart) vs. 10 Gy for 1 fx. All achieved similar levels of palliation. (JCO 2007)

Question 70

How should a tumor characterized as a high-grade neuroendocrine carcinoma, or as large cell neuroendocrine carcinoma, is managed?

Answer 70

Treat per non-SCLC guidelines (NCCN 2018)

Question 71

How should a pt with a carcinoid tumor of the lung be managed?

Answer 71

Sg is 1st line if it is resectable. Some centers will treat atypical carcinoid per the SCLC paradigm (nonsurgical). Per NCCN 2018: 1. Stages I–IIIA typical carcinoid tumor can be observed after R0 resection. 2. For unresectable or medically inoperable stage IIIA or IIB, RT +/– EP is rcvd for atypical carcinoid, and can be considered for typical carcinoid tumors. 3. For atypical carcinoid tumors, resected stage I–II can be observed. However, for resected stages IIIA tumors, adj chemo (EP) +/– RT is recommended.

Question 72

How should stages IIIB–IV or unresectable carcinoid of the lung be managed?

Answer 72

Systemic therapy (EP), or octreotide if octreotide scan positive or symptomatic from paraneoplastic syndrome (NCCN 2018)

Question 73

What is the recommended f/u schedule for SCLC pts?

Answer 73

SCLC f/u schedule: H&P, CT chest/liver/adrenal, and labs at each visit (visits q3–4mos for yrs 1–2, q6mos for yrs 3–5, then annually). PET scan should be considered whenever CT findings suggest recurrence or mets.

Question 74

What is the total lung V20 dose–volume constraint for RT alone and concurrent CRT in definitive lung cancer Tx?

Answer 74

RT alone: V20 <40% | CRT: V20 <35%

Question 75

What is the recommended MLD constraint with definitive RT for lung cancer?

Answer 75

MLD is <15 Gy ideally but not >20 Gy.

Question 76

What is the max cord dose allowed on INT-0096 (“Turrisi regimen”)?

Answer 76

On INT-0096, the max cord dose was 36 Gy (but max dose is 41 Gy in ongoing CALGB 30610 trial).

Question 77

What is the main toxicity associated with using bid RT as done in the Turrisi regimen?

Answer 77

Grade 3–4 acute esophagitis: 27% (bid) vs. 11% (qd). Other toxicities (myelosuppression, nausea) were the same as the qd regimen. This is much less in modern era using 3D or IMRT approaches, with no difference b/t QD vs. BID Tx per CONVERT trial (19% in both arms).

Question 78

What is the distinction b/t grade 2 and 3 pneumonitis (per the RTOG)?

Answer 78

Grade 3 pneumonitis: dyspnea at rest or oxygen supplementation needed Grade 2 pneumonitis: symptomatic and not requiring oxygenation

Question 79

What is the heart dose–volume constraint for RT alone vs. concurrent CRT?

Answer 79

According to CALGB 30610, the following limits are also acceptable: 60 Gy less than one-third, 45 Gy less than two-thirds, and 45 Gy <100%.

Question 80

What is the esophageal dose–volume constraint for RT alone vs. concurrent CRT?

Answer 80

RT alone: V60 <50% | CRT: V55 <50% (ideally, keep the mean dose to <34 Gy per RTOG 0538)