Perioperative chemotherapy has been shown to improve outcomes for resectable gastric cancer compared to surgery alone. Multiple large randomized controlled trials have found that perioperative chemotherapy results in higher R0 resection rates, improved progression-free survival, and overall survival compared to surgery alone. The addition of preoperative chemoradiotherapy to perioperative chemotherapy did not provide additional benefits in overall survival or progression-free survival compared to perioperative chemotherapy alone in one large trial. Ongoing trials are evaluating whether preoperative chemoradiotherapy can be safely added to improve outcomes further.

1. EVIDENCE BASED MANAGEMENT
OF GASTRIC CANCER
Dr Sheetal R Kashid

2. EPIDEMIOLOGY
• Incidence 11.1 per 100000 population and 7.7 deaths per 100000 population
• Eastern Asia 22.4 per 100,000
• India 60,222 6th most common cancer (4.5 per 100,000)
• Male > Female
Globocan 2020

3. ETIOLOGY
Etiology
Genetic
Lynch Syndrome
Hereditary diffuse gastric
carcinoma
Socio-cultural
Salt preserved / high salt foods
Smoked Fish
Smoking
Pathogenic
H. Pylori

4. ANATOMY
• 49% in antrum & distal stomach
• 35% in fundus, cardia at G-E junction
• 25% in body of stomach
• Extensive submucosal lymphatics
• Facilitate intramural spread of tumour
• Difficult to predict the location of involved nodes

5. Regional Lymph Nodes
D1: Perigastric , along lesser and greater curvatures (1-6)
D2: D1 + along celiac and its branches - left gastric, common hepatic and
splenic (7-11)
D3: D2 + Hepatoduodenal, peripancreatic, root of mesentery (12-16)

6. Historical classifications of Gastric Cancer
W.H.O Classification
• Adenocarcinoma 90-95%
• Adenosquamous
• Squamous cell carcinoma
• Small cell carcinoma
• Undifferentiated Ca
Lauren classification
DIFFUSE INTESTINAL
Familial; blood type A Environmental Gastric
atrophy, intestinal
metaplasia
More in women More in Men
Younger Age group Increasing with age
Poorly differentiated;
signet ring cell type
Gland formation
Spreads
transmurally/ via
lymphatics
Haematogenous spread
Decreased E cadherin Microsatellite
instability; APC gene
mutations

8. PATTERN OF SPREAD
Direct extension
Spread beyond stomach wall
Omentum, pancreas, diaphargm,
transeverse colon, celiac vessels,
abdominal wall, adrenal gland,
kidney
Lymphatic spread
Due to abundant subserosal
& submucosal lymphatics
1st to lesser & greater curvature :
perigastric & N1 nodes
Distally: Hepatoduodenal,
perihepatic, root of mesentry,
periaortic
Hematogenous
Liver via portal vein- 30%
Lung , oesophagous
Serosal spread
Surrounding organs &
ligaments

9. • Asymptomatic in early stage
• Anorexia
• Early satiety
• Abdominal discomfort
• Weight loss
• Anemia
• Dysphagia (GEJ tumors)
Clinical Presentation

10. Diagnostic Workup
• History and Physical Examination
• Upper GI Endoscopy- Direct visualisation, Biopsy, Cytology
• Endoscopic ultrasound- depth of invasion
• CT scan of Chest Abdomen and Pelvis:
1. Accuracy for T stage 80% & N stage 66%
2. To rule out distant metastasis
• PET CT:
1. Sensitivity 40%, Specificity 95%, PPV 91%, NPV 56% for Nodal metastasis
2. To rule out distant metastasis in locally advanced disease: accuracy 88%
• Staging laparoscopy: T3-T4 tumors, Nodal involvement, Peritoneal cytology
Seevaratnam R, Cardoso R, McGregor C, et al. How useful is preoperative
imaging for tumor, node, metastasis (TNM) staging with gastric cancer? A
meta-analysis. Gastric Cancer 2012;15:S3–S18.

11. STAGING AJCC 8th Edition

12. SURGERY MAINSTAY OF THE TREATMENT
• Tis/ T1a N0 Lesion: Endoscopic mucosal resection or Endoscopic submucosal dissection (ESD)
• Advanced non metastatic disease: Total or distal gastrectomy with sufficient resection margins of 5cm
• Removal of the peri gastric lymph nodes (D1) as well as those along the main vessels of the celiac trunk
(D2), with the goal of examining ≥16 lymph nodes

13. • Multicentric trial: 80 hospitals
• 50% T2 tumors
• 55% LN positive
• Operative morbidity were significantly higher in D2 group (43% Vs 25%) p <0.001
• Postop mortality higher in D2 group (10% vs 4%) p 0.004
• Morbidity/mortality in the D2 group was mostly attributed to splenectomy
• No significant difference in OS (47% Vs 45%)
• Cumulative risk of relapse at 5 year 29% in D2 Vs 41% in D1 p 0.002
• 15‐year follow‐up showed significantly lower locoregional recurrence and gastric
cancer‐related death rates in D2 than in D1
Dutch Gastric Cancer Group Trial D1
Vs D2 (1999,2010)
711 Patients
380 Patients
D1 Resection
331 Patients
D2 Resection

14. PATTERN OF FAILURE AFTER SURGERY
• Surgery (R0 resection) remains the
treatment of choice.
• 50% patients resectable and localised
at the time of diagnosis.
• Locoregional relapses after R0
resection have been reported to be as
high as 41%-87.5% in various studies.
• 50-70% radically resected cases
relapse and die within 5 yrs.
Failure area MGH
(Clinical)
N=130 (%)
Univ. of Minn.
(Reoperation)
N=105 (%)
McNeer et al.
(Autopsy)
N=92 (%)
Gastric bed 27(21) 58(55) 48(52)
Anastomosis or
stump
33(25) 28(27) 55(60)
Abdominal or
stab wound
- 5(5) -
Lymph nodes 11(8) 45(43) 48(52)

15. Stage IB-IV adenocarcinoma Stomach and GEJ
556 patients
Surgery (Enbloc R0 Resection of all
primary & regional nodes)
Sx f/b Chemo 5FU/LV 1st cycle
CTRT- 45Gy/25# AP/PA conventional technique
5FU/LV D1-4 and last 3 days of RT
2 cycles 5FU + LV 1 month apart
2001
2012
281 patients
275 patients
Chemotherapy: 4weekly
C1 Leucovorin: 20mg/m2 D1-D5 IV
5FU: 425mg/m2 D1-D5 IV

17. • Median f/u- 5yrs
• At 3 year OS 50% vs 27 months 41% (p-< 0.005)
• 5 year OS 43% Vs 28% (HR 1.32 95% CI 1.10-1.60)
Criticism
• D0 Sx– 54%
• D1 Sx- 36%
• D2 Sx- 10%
• Hematologic & GI toxicity in 54% & 33% respectively

18. CONCLUSION:
• First site of recurrence Locoregional in Sx only group
• At 10 year follow up survival advantage
• Adjuvant therapy better than Sx alone in >T3 or N+

19. Can we Improve the Outcomes with addition of Perioperative /
Preoperative chemotherapy?

20. Stage II-IV adenocarcinoma Stomach, GEJ, lower third esophagus
503 patients
Surgery (Radical resection
of primary & nodes
244 underwent treatment
3 Cycles ECF (215 completed)
Surgery (209 underwent Sx))
3 cycles ECF (104 completed)
2006
Epirubicin-50mgm2 D1 IV
Cisplatin- 60mg/m2 D1 IV
5FU – 200mg/m2 CIVI D1-21
253 250
3-6 Wk
6-12 Wk

21. • Higher % patients in chemo arm underwent Curative surgery 79% Vs 70%
• T1/T2 and N0/N1 more in chemo arm
• Only 42% patients could complete protocol
• 34% didn’t undergo postop chemo

22. • D2 only in 43%
• 28% of the surgery only group turned out to be non curative at laparotomy
• Resected tumors were significantly smaller & less advanced in chemo group pCR 8%
• Operative mortality was similar between the group
5 year OS % PFS %
Periopchemo f/b Sx 36.3 30%
Surgery 23 18%
p 0.009 <0.001
CONCLUSION: In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative
regimen of ECF decreased tumor size and stage and significantly improved PFS & OS.

23. • Rationale: 50% patient could receive postop chemotherapy in
MAGIC trial
• So can we change periop-chemotherapy to pre-op alone?
• T3-T4 Ca GEJ or stomach (52.8%)
• To detect with 80% power an improvement in median
survival from 17 months with surgery alone to 24 months
with neoadjuvant, 282 events were required.
• Closed prematurely due to poor accrual
• Median F/up 4.4 years 67 deaths
144 Patients
72 Patients
NACT + Surgery
72 Patients
Surgery Alone
2010
NACT: 2 cycles of 48days
Cisplatin 50 mg/m2 IV D1, 15 & 29
LV 500 mg/m2 IV over 2 hours
5FU 2000 mg/m2 CIVIover 24 hours on D1, 8,
15, 22, 29 & 36

24. NACT f/b
Sx
Surgery p
Median OS 64.6
months
52.5
months
0.466
HR 0.84
R0 resection 81.9% 66.7% 0.036
LN metastasis 61.4% 76.5% 0.018
D2 Gastrectomy 96% 92% NS
Post op
complications
27.2% 16.2% 0.09
CONCLUSION:
• Inadequate statistical power to detect a
potential survival difference.
• Better surgical resection may marginalise
the contribution of NACT

25. 224 Patients
Surgery Alone
111
Perioperative
Chemotherapy + Sx
113
2011
Perioperative Chemotherapy: 2-3 pre op cycles 4weekly
• Cisplatin 100mg/m2 D1 IV
• 5-FU 800mg/m2 D1-5 CIVI
• Post op same regimen 3-4 cycles
• AIM: To evaluate the benefit in OS of perioperative
fluorouracil plus cisplatin in resectable gastroesophageal
adenocarcinoma.
• 144 (75%)-GEJ & 55 (25%)- Stomach
• Median F/up 5.7 year
• 50% received at least 1 cycle of post op chemotherapy
• 38% in chemotherapy group experienced Grade III/IV toxicity

26. Periop
chemo + Sx
Surgery
alone
p
5 year OS 38% 24% 0.02
HR 0.69
5 year DFS 34% 19% 0.003
HR 0.65
R0 resection 84% 73% 0.04
Post op
complications
25.7% 19.1% 0.24
CONCLUSION:
In patients with resectable adenocarcinoma of the
lower esophagus, GEJ or stomach, perioperative
chemo using fluorouracil plus cisplatin significantly
increased the curative resection rate, DFS & OS.
Planned sample size was not accrued and trial
stopped early due to poor accrual

27. • 12 RCT from 1990-2012
• 1820 Patients of resectable Gastric or GEJ Ca
• NACT showed statistically significant benefit for
1. OS: OR 1.32 (95% CI: 1.07 – 1.64)
2 . PFS: OR 1.85 (95% CI: 1.39 – 2.46)
3 . Higher R0 resection OR: 1.38 (95% CI: 1.08 – 1.78)
4. No significant worsening of operative
complications
2014

28. April 2019
716 Patients
356 FLOT 4 X4
Surgery
FLOT 4 X 4
360 ECF/ ECX X 3
Surgery
ECF/ ECX X 3
FLOT 4 every 2 week:
• Docetaxel 50mg/m2 D1 IV
• Oxaliplatin 85mg/m2 D1 IV
• LV 200mg/m2 D1 IV
• 5FU 2600mg/m2 D1 IV
24Hr repeated every 2wk
ECF/ECX: every 3 week
• Epirubicin 50mg/m2 D1 IV
• Cisplatin 60mg/m2 D1 IV
• 5FU 200mg/m2 IV D1-21 CIVI
• or capecitabine 1250mg/m2 P/O
• Docetaxel has showed benefit in metastatic gastric
cancer and GEJ cancer
• Compared Two different chemotherapy regimens
• 28 German centers
• Stomach 44%
• GEJ 56%
• cT2-4/cN any/cM0

29. Toxicity in FLOT Trial

30. FLOT ECF/ECX p
2 year OS 68% 59% 0.012
HR 0.77
3 year OS 57% 48% 0.012
Median DFS 30 months 18 months 0.0036
HR 0.75
Post op
Complication
51% 50% NS
SAE 27% 27% NS
R0 Resection 85% 78% 0.0162
Conclusion: In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma,
perioperative FLOT improved overall survival compared with perioperative ECF/ECX.
NEW STANDARD OF CARE

31. • Perioperative chemotherapy / Neoadjuvant chemotherapy improved survival
in patients with resectable gastric cancer
• Can addition of chemo-radiotherapy to perioperative chemotherapy improve
outcomes?

32. Stage IB-IVA adenocarcinoma Stomach,Seiwert II/III
788 patients
3cycles of X 21 day
Curative Surgery (326 underwent Sx))
CTRT- 45Gy/25#, capecitabine- 575mg/m2 twice daily on days of RT
Cisplatin- 20mg/m2 IV D1 of each week (197 completed)
Curative Surgery (310 received)
3 cycles postop chemo (180 completed)
3 cycles similar chemo regimen (321 completed)
2018
Epirubicin 50mg/m2 IV
Cisplatin 60mg/m2 on D1 IV
Capecitabine 1000mg/m2 BID D1-14
Epirubicin 50mg/m2 IV
oxaliplatin 130mg/m2 on D1 IV
Capecitabine 625mg/m2 BID D1-21
393 patients 395 patients
(334 completed)

33. •40% patients were early stage unlikely to benefit from
any adjuvant therapy
•50-60% of patients completed adjuvant treatment

34. CONCLUSION:
• No benefit of addition of chemoradiotherapy to perioperative
chemotherapy over perioperative chemotherapy and surgery.
Median F/up
61.4 months
Periop
chemo + Sx
Priopche
mo + Sx +
RT
p
Median OS 43 months 37 months 0.90
HR 1.01
Median EFS 28 months 25 months 0.92
HR 1.19

35. 2017
Trevor Leong et al
Purpose: To evaluate safety and benefit of adding Preoperative
CTRT to Perioperative chemotherapy
Primary Objective: To evaluate whether perioperative ECF plus
CTRT improves OS as compare to ECF alone
25% GEJ
75% Stomach
Stage Ib-IIIc
120
60 60

36. Conclusions: These results demonstrate that preoperative chemoradiation can be safely delivered to the vast
majority of patients without a significant increase in treatment toxicity or surgical morbidity.
FINAL RESULTS ARE AWAITED

37. Perioperative Chemotherapy
Advantages
• Downstaging T/N
• Improves R0 Resection
• Delivering CT before Surgery
• Easier and better Tolerated
• Better Compliance
• OS Benefit (3 RCTs)
• Prevents futile surgery in progressors
Disadvantages
• Residual Tumors exposed to same therapy
again
• Post op portion delivery remains a challenge
Indication: ≥ cT2 AnyN
Contraindications:
1. Gastric outlet obstruction
2. Active bleed
3. Poor PS

38. Conclusion Of Neoadjuvant / Perioperative chmoetherapy trials:
• OS Benefit
• For all T2N0 or above stages of gastric adenocarcinoma perioperaive chemotherapy is standard of
care (Specially Bulky T3/T4, visible perigastric nodes or linitis plastica)
• FLOT 4 is the standard regimen at present
• Old regimen ECF/ECX are toxic and outdated
• In case of poor PS and Multiple comorbs FOLFOX or CAPOX can be used
• At present there is no role of perioperative chemoradiotherapy over perioperative chemotherapy alone.
FLOT every 2 week: 4 cycles
pre op and 4 cycles Post OP
• Docetaxel 50mg/m2 D1 IV
• Oxaliplatin 85mg/m2 D1 IV
• LV 200mg/m2 D1 IV
• 5FU 2600mg/m2 D1 IV 24Hr
repeated every 2wk

39. Can we Improve the outcomes with addition of post operative
chemotherapy?

40. • AIM: To evaluate role of S1 as adjuvant chemotherapy in gastric cancer
• S1 is combination of tegafur, gimeracil and Oteracil
• Pathological Stages II and III
• D2 gastrectomy in 95% & D3 Gastrectomy in 5%
• 89% had lymph node metastasis
• Median F/up 3 years
• Less than 6% experienced Grade III toxicity
1059 Patients
Surgery Alone
539
Surgery f/b S1 from 6
weeks post Sx to 1 year
529
2007 & 2011
update
S1: Tegafur + Gimeracil + Oteracil
• 6 week cycle
• 80mg/m2 orally daily X 4weeks
• 2 weeks off

41. • CONCLUSION: Adjuvant chemotherapy with oral S-1 had significant overall
survival benefit in east asian patients who underwent D2 LND.
• STANDARD OF CARE IN JAPAN
• 3‐year OS 80.1% in S1 group vs 70.1% in surgery alone group p 0.002
• 5 year OS 71.7% S1 group vs surgery alone group 61.1% (HR 0.669)
• 5year RFS 65.4% S1 group Vs surgery alone group 53.1% (HR 0.653)
• Surgery is the Key: High Quality surgery in Japan

42. 2010
• IPD Metaanalysis
• 17 Trials (3838 patients)
• To quantify OS & DFS benefit with adjuvant chemo Vs Surgery alone
• Flurouracil based chemotherapy used
• Median follow up 7 years
• Adjuvant chemo showed significant benefit in terms of OS (HR 0.82;
95% CI, 0.76-0.90; P.001) & DFS (HR 0.82; 95% CI, 0.75-0.90;
P.001).
• 5 year OS increased from 49.6% to 55.3% with chemotherapy.
CONCLUSION: Postoperative adjuvant chemotherapy based on fluorouracil regimens was associated with
reduced risk of death in gastric cancer compared with surgery alone.

45. • AIM: To evaluate effect of adjuvant chemotherapy with
capecitabine and oxaliplatin after D2 gastrectomy in
gastric cancer
• Done in Korea China & Taiwan
• Stage Ib-IVA
• 98% Gastric Cancer
• Curative D2 gastrectomy was carried out within 6 weeks
before randomisation.
• At least 15 lymph nodes were examined to ensure
adequate disease classification
1035 Patients
515 Patients
Surgery alone
520 Patients
Surgery f/b adjuvant
chemotherapy
2012 2014
• Eight 3-week cycles of Capecitabine
(1000 mg/m2 BID on D1–14)
• IV Oxaliplatin 130 mg/m2 on D1
• Only 67% of t h e p t s in t h e chemo a r m
received all 8 cycles of chemotherapy
• 90% p a t i e n t s - dose modifications
i/v/o adverse events

46. Medain F/up 62 mo 3 yr DFS 3 yr OS 5 yr OS 5 yr DFS
Adj Chemo 74% 83 % 78% 68%
Surgery Only 59% 78% 69% 53%
p <0.0001 0.0493 0.0015 <0.0001
CONCLUSION: Adjuvant treatment with capecitabine plus
oxaliplatin after D2 gastrectomy should be considered for
patients with operable stage II or III gastric cancer.
Adjuvant chemotherapy (CAPOX) became the standard of
care in East Asia

47. AIM: To prove the superiority of postop S-1 plus docetaxel
over S-1 alone for R0 resection of pathologic stage III gastric
cancer.
Primary End point: 3 year RFS
Median F/up 12.5 months
3year RFS in S-1 plus docetaxel (66%) to S-1 (50%) (HR
0.632; 99.99% CI, 0.400 to 0.998, P .001)
Grade ¾ adverse events higher in S1 + docetaxel group
Enrolment was terminated as recommended by the
independent data safety committee.
CONCLUSION: Addition of docetaxel to S-1 is effective with few safety concerns in patients with stage III
gastric cancer.
915 Patients
D2 Sx
454 Patients
Adj S1 + Docetaxel
459 Patients
Adj S1 alone
2019

48. 34 studies with 7824 patients treated with adjuvant chemotherapy in D2 resected Gastric cancer
Adjuvant Chemotherapy in resectable Gastric cancer gives 15% OS benefit and 21% DFS Benefit at 5 year
2013

50. Can we improve outcomes of adjuvant chemotherapy by
adding RT after D2 resection?

51. Stage IB-IV adenocarcinoma Stomach R0 enbloc resection of primary and D2 dissection
458 patients
6 cycles (XP) capecitabine (1000mg/m2
BD, D1-14) +
Cisplatin (60mg/m2, D1) every 3 weeks
172 completed
2 Cycles XP
(227 received)
CTRT- 45Gy/25# AP/PA conventional technique
capecitabine-825mg/m2 BD daily (203 received)
2 cycles XP every 3 weeks (188 completed)
2012
2015
228 patients 230 patients

52. Median f/u-53
months
Node
positive

53. CONCLUSION:
• No benefit of postop CTRT over adj chemo in D2 dissection
• ??Benefit in node positive patients
• Too few events after 53 months median f/u
Criticism:
• Even though ARTIST trial met accrual goal, both arm did better than
anticipated
• So number of events was smaller than planned
• Resulting in the study being underpowered for planned endpoints

54. ARTIST 2: Interim results of a phase III trial involving adjuvant
chemotherapy and/or chemoradiotherapy after D2-gastrectomy in
stage II/III gastric cancer (GC)
pathologically-staged II or III, node-positive, D2-resected GC
538 patients
adjuvant S-1 (40-60mg/m2 bid
4-weeks-on/2-weeks-off) for
one year
SOX for 2 cycles, then CTRT 45 Gy with S-1 40 mg
bid daily, f/b additional SOX for 4 more cycles
(SOXRT)
S-1 (40 mg/m2 bid 2-
weeks-on/1-week-off)
plus oxaliplatin 130
mg/m2 (SOX) for six
months
DFS at 3-years was found to be 65%, 78% and 73% in S-1, SOX and SOXRT arms,
respectively.
No difference in DFS between SOX and SOXRT was found (HR 0.910, P = 0.667).
May 2019

55. • It compared INT0116 protocol regimen vs
postop ECF (MAGIC trial) before and after
FU plus concurrent RT.
• GEJ 22%
• Stomach 78%
• T3 & T4 55%
• D2 resection in 55%
546 Patients
Surgery
280 Patients
5FU/ LV X 1 +
5FU IVCI + RT
f/b 5FU/LV X 2
266 Patients
ECF X 1
5FU IVCI + RT
ECF X 2
2018
• 5FU/LV:5-FU 425 mg/m2/day D1-5 +
• LV20mg/m2/day D1-D5
• RT: 45Gy/25# with concurrent 5- F U (200
mg/m2/day CIVI)
• ECF:Epirubicin:50mg/m2 D1 Cisplatin 60mg/m 2
D1 5FU 200mg/m2/day D1 -D21

56. CONCLUSION: Following curative resection of gastric or GEJ adenocarcinoma, postoperative CTRT
using ECF before and after 5-FU/RT does not improve survival when compared to bolus 5-FU/LV before
and after 5-FU/RT.
5 year OS % DFS %
FU + LV + RT 44% 37%
ECF + RT 44% 39%
p 0.69 0.94
Median F/up 6.5 year
ECF arm was better tolerated

57. Conclusion of adjuvant Trials:
• For patients who have already undergone potentially curative surgery with no neoadjuvant therapy adjuvant
chemotherapy is recommended as compare to surgery alone (stage T1N1, above T2N0)(CLASSIC).
• After D2 dissection there is no benefit of adjuvant RT (ARTIST 1 & 2, CALGB)
• For patients who have undergone less than D2 dissection or <16 LN dissected adjuvant chemoradiotherapy is
preferred (INT 0116).
• CAPOX is preferred regimen for adjuvant chemotherapy
• S1 is standard of care in Japan (S1 + Docetaxel is toxic but beneficial)
• Poor PS patients: FU/LV
• CAPOX
• Eight 3-week cycles
• Capecitabine (1000mg/m2 BID D1–14)
• IV Oxaliplatin 130 mg/m2 on D1

58. Perioperative & Adjuvant Therapy in Gastric Cancer
Trial OS Benefit
INT 0116 US (with CTRT) 10% OS at 5 year HR 0.65
MAGIC UK 13% OS at 5 year HR 0.75
ACTS GC S-1 Japan 10% OS at 5 year HR 0.67
CLASSIC Asia 9% OS at 5 year HR 0.66
FLOAT4 Germany 9% OS at 3 year HR 0.77

59. TMH Protocol
• Adjuvant RT (INT 0116)
• Less than D2 surgery, Margin Positive, <16LN resected
• Perioperative Chemotherapy for >=T2N+ (FLOT 4)
• Modified FLOT 4 Regimen: Docetaxel 50mg/m2 on D1
• Oxaliplatin 85mg/m2 on D1
• 5FU 2400mg/m2 infusion over 48 hours every 2week X 4 cycles
• 4 Cycles of same regimen post Sx
• For Patients who underwent emergency upfront Sx: (CLASSIC)
• CAPOX every 3 week for 8 cycles

60. Based on geographic area and randomized trials wide variation in practice of adjuvant therapies

62. SUMMARY